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United States District Court, N.D. California
May 5, 2014
HEDDI LINDBERG, Plaintiff,v.WELLS FARGO BANK N.A., et al., Defendants.
PHYLLIS J. HAMILTON, District Judge.
Before the court is defendant Wells Fargo Bank, N.A.'s ("defendant") motion for attorneys' fees, filed on January 2, 2014. Defendant seeks a fee award in the amount of $36, 479.04, to be assessed against plaintiff's counsel, Vernon L. Bradley. Mr. Bradley did not file an opposition to the motion. Having considered the papers filed in connection with defendant's motion, the court hereby GRANTS in part and DENIES in part defendant's motion for attorneys' fees.
The factual background of this mortgage case is set out in this court's order denying plaintiff's motion to remand and granting defendant's motion to dismiss the first amended complaint. See Dkt. 35. To summarize the procedural background, plaintiff first filed suit in state court on February 8, 2013, and defendant removed the case to this court on February 21, 2013. On March 15, 2013, plaintiff filed an amended complaint, and on the same day, filed a motion for preliminary injunction. The court held a hearing on the preliminary injunction motion on April 17, 2013, and issued an order denying the motion on April 22, claims. See Dkt. 27.
The court then held a hearing on plaintiff's motion to remand and defendant's motion to dismiss, and on July 9, 2013, denied the motion to remand and granted the motion to dismiss. See Dkt. 35. The dismissal was with prejudice as to the majority of plaintiff's claims (which related to the origination of plaintiff's loan, defendant's standing to foreclose, and defendant's alleged dual-tracking), but plaintiff was given leave to amend as to any claims that were "based on plaintiff's attempted loan modification." Id . Plaintiff was given until August 8, 2013 to file a second amended complaint.
Plaintiff did not file an amended complaint by the deadline, and instead filed a notice of appeal to the Ninth Circuit on August 8, even though the court's dismissal order granted leave to amend on certain claims and was thus not a final, appealable order. See Dkt. 36. Then, on September 25, 2013 (while plaintiff's appeal was still pending), plaintiff also filed an "ex parte application for entry of order staying foreclosure pending appeal and demand for reinstatement amount." See Dkt. 42. The next day, defendant filed a response indicating that it had already provided plaintiff with a reinstatement amount. See Dkt. 43. On September 27, 2013, the court issued an order denying plaintiff's application, noting that the application was moot to the extent that it sought a reinstatement amount, and that in all other respects, it was duplicative of plaintiff's already-denied motion for preliminary injunction. See Dkt. 45.
Then, plaintiff went back to the Ninth Circuit, and filed an "emergency motion for injunction pending appeal" on October 2, 2013. The Ninth Circuit denied the motion, and on October 16, 2013, the Ninth Circuit issued an order indicating that it may lack jurisdiction over plaintiff's appeal, because "the district court's order dismissing the complaint with leave to amend is not a final, appealable order." Plaintiff was directed to "move for voluntary dismissal of the appeal or show cause why it should not be dismissed for lack of jurisdiction." Plaintiff failed to respond to the order, and on November 25, 2013, the appeal was dismissed for failure to prosecute.
After the appeal's dismissal, defendant moved this court for an order dismissing the complaint with prejudice, based on plaintiff's failure to comply with this court's July 9, 2013 order directing her to file a second amended complaint. Plaintiff did not oppose the motion, and on December 19, 2013, the court dismissed the complaint and entered judgment in favor of defendant. The court's dismissal order was based on plaintiff's failure to (1) file an amended complaint in response to this court's July 9, 2013 order, (2) respond to the Ninth Circuit's October 16, 2013 order, and (3) oppose or otherwise respond to Wells Fargo's motion to dismiss. See Dkt. 50. Defendant now moves for an award of attorneys' fees to be assessed against plaintiff's counsel, Mr. Bradley.
Defendant's motion is largely based on a contractual attorneys' fee provision contained within the promissory note and deed of trust on the subject property. However, as noted above, defendant does not seek fees from plaintiff, and seeks fees only from plaintiff's counsel himself, who was not a party to either of these contracts. While some courts within this district have assessed fees against a plaintiff's counsel based on a contractual attorneys' fee provision, this court declines to do so here. Thus, to the extent that defendant seeks an award of attorneys' fees from Mr. Bradley based on provisions contained within the promissory note and deed of trust, the motion is DENIED.
However, aside from the contractual fee provision, defendant also seeks fees based on 28 U.S.C. § 1927, which allows the court to award fees against "any attorney... who so multiplies the proceedings in any case unreasonably and vexatiously." Defendant also notes that the court has the authority to order sanctions against an attorney for bad faith conduct in litigation. Primus Automotive Financial Services, Inc. v. Batarse , 115 F.3d 644, 648 (9th Cir. 1997); see also Roadway Express, Inc. v. Piper , 447 U.S. 752, 767 (1980). Because any award of fees will be assessed against Mr. Bradley, and not plaintiff herself, the court will base its findings on section 1927 and on the court's power to sanction, rather than on the contractual attorneys' fee provision. Thus, the court will not award the entire amount sought by defendant, and will instead determine a fee award amount based on the extent to which Mr. Bradley multiplied the proceedings unreasonably and vexatiously and/or acted in bad faith.
In its motion, defendant argues that the procedural history of this case "reflects a number of frivolous and meritless filings, unsupported by any facts, which were brought only to delay the foreclosure sale, " and points out five specific examples: (1) plaintiff's motion for preliminary injunction, (2) plaintiff's motion to remand, (3) "ruling on Wells Fargo's motion to dismiss, " which discusses the dismissal of plaintiff's first amended complaint (with leave to amend only on loan-modification-related claims) and plaintiff's appeal to the Ninth Circuit, (4) plaintiff's ex parte application to delay the foreclosure sale, and (5) "Wells Fargo's motion to dismiss for failure to prosecute, " which also refers to plaintiff's failure to file a second amended complaint.
The court finds that some, but not all, of these filings led to unreasonable and vexatious multiplication of the proceedings and/or constituted bad faith.
First, as to plaintiff's motion for preliminary injunction (category (1) above), the court disagrees that it was "frivolous and meritless." The court notes that, while this case was still in state court, plaintiff had obtained a temporary restraining order preventing foreclosure, and the state court had set a hearing on plaintiff's motion for preliminary injunction. After defendant removed the case, plaintiff filed a motion for preliminary injunction in this court. While the court ultimately denied plaintiff's preliminary injunction motion, it did find that plaintiff's loan-modification-related arguments could not be "easily reject[ed]." See Dkt. 27. Thus, the court does not find that plaintiff's counsel acted unreasonably, vexatiously, or in bad faith by filing the preliminary injunction motion.
Second, the court disagrees with defendant's characterization of plaintiff's motion to remand (category (2) above) as "clearly frivolous." The remand motion was based on the argument that Wells Fargo is a citizen of California, its principal place of business, as well as South Dakota, its state of association. That argument has been accepted by at least one court in this district. See Martinez v. Wells Fargo Bank , 946 F.Supp.2d 1010 (N.D. Cal. 2013). While this court ultimately declined to follow Martinez, it does not find that plaintiff's counsel acted unreasonably, vexatiously, or in bad faith by attempting to persuade the court to do so.
Defendant's arguments regarding category (3) are less than clear, as its motion mentions the dismissal of plaintiff's first amended complaint, and also discusses plaintiff's appeal to the Ninth Circuit, which was ultimately dismissed for failure to prosecute. Defendant does not explain how the court's "ruling on Wells Fargo's motion to dismiss" constituted unreasonable, vexatious, or bad faith conduct on the part of Mr. Bradley - while the failure to file an amended complaint in response to the order was indeed unreasonable, the only fees incurred in connection with that conduct are covered by category (5). And while the court strongly agrees that Mr. Bradley's appeal of a non-final order was indeed unreasonable, vexatious, and in bad faith, defendant has expressly stated that it "is not seeking to recover its attorneys' fees for work on the appeal." See Dkt. 52-1 at 4. Thus, the court will not award any fees under section 1927 based on category (3).
As to category (4), the court agrees that Mr. Bradley's conduct was unreasonable, vexatious, and in bad faith. Having already lost the motion for preliminary injunction, Mr. Bradley simply re-filed that same motion in a different guise. The court said as much in its order denying the application, noting that "plaintiff has already moved this court for a preliminary injunction, based on the same arguments presented in this motion, " and that "[a]ll of these arguments were considered and rejected by this court in its denial of plaintiff's preliminary injunction motion." See Dkt. 45. Thus, the court will award fees under section 1927 for the conduct in category (4).
Finally, as to category (5), the court finds that Mr. Bradley acted unreasonably, vexatiously, and in bad faith by failing to respond to the court's July 9 order, which necessitated the filing of defendant's motion to dismiss for failure to comply with a court order. Thus, the court will award fees under section 1927 for the conduct in category (5).
As stated above, the court will award fees under section 1927 for the conduct in categories (4) and (5). Though defendant does not specifically delineate which portion of the requested fees correspond to the above categories, it does provide a timeline of fees incurred, which allows the court to determine the proper fee amount attributable to each category.
The conduct described in category (4) occurred in September 2013. During that month, defendant incurred $1, 174 in fees, $1, 033.12 of which were ultimately paid after its client discount. Thus, the court awards $1, 033.12 in fees based on category (4).
The conduct described in category (5) occurred during November 2013. During that month, defendant incurred $1, 227.50 in fees, $1, 080.20 of which were ultimately paid after its client discount. Thus, the court awards $1, 080.20 in fees based on category (5).
Based on the foregoing, defendant's motion for attorneys' fees is GRANTED in aprt and DENIED in part. Plaintiff's counsel, Vernon Bradley, is ordered to pay attorneys' fees to defendant in the amount of $2, 113.32.
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Large | Male
Mr. Rex is a lovable 5-year-old German Shepherd. He loves everyone! He is strong and has not been trained to walk on a leash. We are working on it with him and he is smart and is learning quickly. Mr. Rex was left abandoned by his family when they moved. We are so happy to be able to help him find his second chance! He will be a loyal, loving companion!


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Palo Alto Weekly 25th Annual Short Story
The Kitchen Maid's Apprentice
Cook told me to mind the potato soup. I didn't know Cook's name, and for all the years that I had been her apprentice in the castle, I had never called her anything else.
Judge's comment
"This is a very well-crafted story, rich in language with effectively chosen historical details."
Palo Alto Weekly Holiday Fund
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Testo Again And Again
- Home
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- Illuminare (2006)
- >
- Again And Again
Fabio Rovazzi: arriva laccusa di plagio
So where is the piano and the big bass drum? And the clashing of cymbals. I need some running frantic notes, some lines of panic and depseration. Cause your infatuation demands satisfaction. I'm trying my best. I won't quit. Im trying not to disappoint. Again and again. Here we go just to balance you out. I'm on fire, and this is about how our song came on and we sang along. So sing along. The pictures are all falling down. The ground started shaking without you around. So where are you? I'm so lost. I'm running through town screaming curses and you cleared out all the poison
- Dignified Exit Society
- The City Lights
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- We Fall
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Quick Look
Property brokered by
Get more listing details on brokerage site
Presented By:
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(800) 210-0321
Email Agent
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Property DetailsCome see this fantastic home just a short distance from the lake. Only a few years old and very well taken care of. Kitchen has tons of storage. Master suite has walk-in closet and nice bathroom with garden tub, double vanity, and separate shower. 2nd BR has a large walk in closet. Bonus room is being used as an office now but easily could be a 3rd sleeping area when you have guests over. Wired storage building. Great new deck. New water heater in 2016. Paved driveway. TV in dining room stays! MUST SEE
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Additional Property InformationThis single family listing located at 6451 Reidsville Road, Belews Creek, NC has two bedrooms and two bathrooms. A 1 story, ranch style property, it is currently availible at $129,900.
Additional features include ceiling fan(s), dead bolt(s), garden tub, laundry room - main level, separate shower, deck, paved drive.
This property is presented by Ryan Sharpe of Allen Tate Company - Charlotte headquartered in North Carolina.


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16 August 2007 12:08:22
TenTonHammer interview Matt Friorposted by Dark0ne Game NewsWhile Zenimax Online, sister company to Bethesda recently setup to focus on MMOG's, is not directly related to the Elder Scrolls series I think keeping on top of their plans might well be interesting to some (as it is interesting to me).
Matt Frior has been in the lime-light a lot recently after it was announced he has been pulled in from MMO developers Mythic (Dark Age of Camelot, Warhammer Online) to head Zenimax Online. This "pinging" interview with Matt focusing on the inception and direction of Zenimax Online.QUOTETen Ton Hammer: Can you tell us a little about the direction that ZeniMax plans to take in regards to an MMOG? Are there any game concepts in the works already?
Matt: I've only been on the job a little while, so we're putting our strategy together right now. We've kicked around some concepts and ideas, but nothing concrete yet. We'll announce those when the time is right.
Still no word on a game concept or whether it will be based on a current franchise. I guess we'll just have to wait and see.
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Tag: funny
What happens when you dress up for Halloween as your dog's favorite chew toy
For your Halloween viewing pleasure we present a California dog named Jolene, coming face to face with a life-sized version of her favorite chew toy.
Jolene's owner, Emily Crisp, thought it might be fun, for Halloween, to have her boyfriend, Ben Mesches, dress up in a Gumby costume.
He walks into the room as Jolene is enjoying some time with her Gumby chew toy. Jolene looks up and registers a look of what can only be described as wonder and amazement.
She cautiously, at first, approaches the life-sized Gumby, jumps up on him, and proceeds to go crazy with joy.
Mesches, of Petaluma, initially posted the video to his Facebook account. On YouTube, it has gotten, nearly 4 million views in two weeks.
Happy Halloween, Jolene, and everybody else.
Posted by John Woestendiek October 31st, 2016 under Muttsblog, videos.
Tags: animals, ben mesches, chew, chew toy, costume, dog, dogs, dress up, emily crisp, favorite toy, funny, golden retriever, gumby, halloween, jolene, life sized, meeting, pets, reaction, toy, video, youtube
Comments: none
Do we really want to read our dogs' minds?
Devices claiming to translate what your dog is thinking into human words have been popping up on the Internet for a good five years now, and some of the more gullible among us have bought them — and even contributed to campaigns to bring them to market.
There's No More Woof an electronic device — still in the testing stages, of course — that Swedish scientists say will be able to analyze dogs' brain waves and translate their thoughts into rudimentary English.
There's the slightly more real but far more rudimentary Bow-Lingual, which claims to be able to translate your dog's barks into emotions, currently unavailable on Amazon.com
There are apps — real and prank ones — that offer dog-to-human translations, virtually all of which have disclaimers saying that they should be used primarily for entertainment purposes.
And there are legitimate research projects underway around the world, with real scientists and animal behaviorists seeking to determine and give voice to what is going on in the heads of dogs.
But wait a minute. Do we really want to know?
As this bit of satire shows, we might not like the result.
It was produced by Los Angeles-based Rogue Kite Productions, an independent film company created by writer/producer/director Michelle Boley and camera operator/editor Taylor Gill, who pursue projects of their liking when not doing their day jobs.
Their spoof depicts a speech articulating device much like one a group in Sweden claims to actually be working on.
No More Woof aims to "break the language barrier between animals and humans," the Sweden-based Nordic Society for Invention and Discovery (NSID) says on its Indiegogo page.
NSID says the device records electroencephalogram (EEG) readings from a dog that are then analyzed by a Raspberry Pi microcomputer and translated, through a small speaker, into simple phrases like, "I'm hungry," or "Who is that person?"
Popular Science declared the project almost certainly bogus — and yet money keeps pouring in from donors.
The No More Woof indiegogo page says more than $22,000 has been contributed to the project.
Not to cast aspersions on the Swedish group's attempt to move technology ahead, but I think Rogue Kite Productions could put that money to better use.
Posted by John Woestendiek May 31st, 2016 under Muttsblog, videos.
Tags: animals, apps, articulating, bow-lingual, bowlingual, communicate, communications, devices, dog, dogs, emotions, funny, humans, humor, minds, no more woof, owners, pets, reading, rogue kite productions, speech, thinking, thoughts, translate, translation, video, words
Comments: 1
Stella!!! So much for that fence
We can't attest to how genuine this video is — some commenters suspect it was staged — but it's pretty funny all the same.
The video was uploaded to YouTube earlier this month by someone using the name Joe Ballew. And it looks like it could hit the million-view mark before the month is out.
In it, a male voice, presumably Ballew's, can be heard showing off his newly repaired fence.
"Yep, just completed fixing this fence. Pretty proud of it I'd have to say," the man says. "Kinda keeps Stella in the yard."
Just how "kinda" becomes obvious seconds later — when Stella comes into the frame and easily jumps over what appears to be the new section of fence.
"Dammit," the man can be heard to say.
What makes some viewers suspicious is that just before Stella appears, the otherwise smooth camera work is interrupted with a jolt, and a slight human grunt can be heard — almost as if the camera operator is throwing something he knows Stella, fence or no fence, is going to go after.
We, too, might question how straightforward Ballew is being, but we are still mighty impressed with Stella's jumping ability.
Posted by John Woestendiek March 24th, 2016 under Muttsblog, videos.
Tags: animals, dog, dogs, escapes, fence, fences, fencing, funny, home, jump, jumping, leap, leaping, pets, stella, video, yard
Comments: none
Amy Schumer on moms and their fur babies
A doggy day care center is the setting for this Amy Schumer skit, poking fun at those dog owners who go a little bit overboard — especially when it comes to describing their own "heroism" in adopting rescue dogs.
The five moms trade stories after dropping their "fur babies" at day care.
One explains her dog "lost his legs when a cop shot him in St. Louis."
Not to be outdone, another says her dog was a Sudan child dog soldier who was kicked out of the militia because he was gay.
Another comes in with a dead dog, explaining she adopted him after he was put down at the local pound: "And I was like, 'I'll take her.' I'm just doing what any hero would do."
Another relates the story of rescuing her dog, Mrs. Belvedere, from Hurricane Katrina.
"She was up on the roof with this little boy whose parents had drowned. And I just thought, 'That little orphan boy can't take care of a dog.' So I choppered in and rescued her right off that roof."
"What happened to the boy?" Schumer asks.
"What boy?" the owner of Mrs. Belvedere responds.
Posted by John Woestendiek May 26th, 2015 under Muttsblog, videos.
Tags: amy schumer, animals, comedy, comedy central, day care, dogs, funny, fur babies, humor, inside amy schumer, pets, rescues
Comments: 2
So he ain't no Willie Mays
He isn't exactly adept at catching airborne snacks in his mouth. Does that mean Fritz the Golden retriever should be made a laughingstock?
Probably not, but welcome to the Internet age, in which dogs (and humans) are more likely to become famous not for doing something right, but for doing something wrong — and the more "epic" the fail the better.
This video was posted on YouTube last week, and since has been reposted on major media websites, and broadcast on TV, like yesterday's Today Show — all but guaranteeing it will go viral.
We hesitated before even posting it, because in a way we see it as laughing "at" Fritz, who, for all we know, might have a vision problem or other disability.
But we admire his persistence, and the look of determination in his eyes. We admire that far more than we admire the owner, and — assuming Fritz is eating everything thrown at him after it lands on the ground — the unhealthy diet he is providing his dog.
Fritz flubs it when he tries to catch, among other food items, a donut, a slice of pizza, a hot dog (on bun, with mustard), a chimichanga and more.
Not until the very end does he manage to catch an item — what appears to be a french fry.
The YouTube post provides few details, so we can only hope this was videotaped over time, as opposed to all in one day — for the sake of Fritz's stomach, and his owner's carpeting.
Posted by John Woestendiek March 25th, 2015 under Muttsblog, videos.
Tags: animals, catching, dog, dogs, error, fail, food, fritz, funny, golden retriever, humor, internet, miss, missing, pets, snacks, treats, video, videos, youtube
Comments: 1
Karma as it should be — instant
This man was having a pretty good chuckle as he took video of his dog slipping and sliding on the ice at Brooklyn's McGolrick Park
Mere seconds later, he took a dive himself.
We love it when karma works quickly.
In the dog owner's defense, he apparently cared about his dog enough to equip him with booties. He chuckled again after he took his own fall.
And he had enough humility to post himself getting his comeuppance (or in this case, comedownance) on YouTube.
Posted by John Woestendiek February 11th, 2015 under Muttsblog, videos.
Tags: animals, dog, dogs, falling, falls, funny, ice, karma, mcgolrick park, new york, owner, pets, slide, slip, video, walker
Comments: none
Diary of a sad dog
Ten million viewers have listened to the astute ramblings of these "sad dogs" since they were posted on YouTube a year and a half ago by someone calling himself Ze Frank.
"Sad Dog Diary" is the sequel to Sad Cat Diary, and while it's laden with poop and pee references, it offers some hilarious insights into how dogs might see the world — were they as logical and unexcitable as the moderator who provides their voice.
Posted by John Woestendiek November 12th, 2014 under Muttsblog, videos.
Tags: animals, behavior, dog diary, dogs, funny, humans, pets, sad, sad dog diary, video, youtube
Comments: none


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So I want to be better organized this year.
Hoping for things to run just a little more smoothly and reduce the stress of my schedule.
You too?
While I'm not one to make many New Year's Resolutions, I can't help but acknowledge that this is a good time of year to stop.
And see where I can improve.
Not merely for my own sake, mind you, but also for the sake of my marriage and for my family.
Now do you want to know what I want to work on? Where I hope to be better organized?
Okay, I'll tell you a few…..
I would like to get back to meal planning. There've been too many nights over the past few months where I've had to scramble to figure out dinner. And while I could blame a number of circumstances, the responsibility comes down to me. I'm thinking I'll either return to my Simple Menu Planning and/or try out Chelsia's Weekly Menu Plan.
Closely related to the goal above, I want to go back to shopping lists—especially grocery shopping. Ugh. I don't even want you to know how bad I've been with this lately. I have to remember that lists are my friends. Saves time, money, and stress.
I want to write down all appointments and plans. And not only my own, but also those of others in my family. Increasingly, we are scattered in many directions and if I want to make family plans (or a nice family dinner, ahem!), then I need to know what works…and what doesn't.
I want to carve out set-aside time for rest and refreshment. I've noticed that if that time isn't purposely marked out, then most days and many hours get filled. And it's too much. So I'm looking forward to designating chunks of time where we don't have anything on the calendar. (Doesn't that sound lovely, though?)
And speaking of calendars, that brings us to the best tool I've found for becoming better organized.
The Homemaker's Friend Daily Planner
Not to long ago, I shared with you 3 reasons why planning makes me happy and why this planner is my favorite. But for those of you who missed it, I'll give you a quick recap on why I like this planner so much. My friend, Sue – whom I've known ever since our kids were itty-bitty – created this planner and I've been using it ever since. It's truly the best I've found.
Here's why:
- It's pretty. (Don't you think it's nicer to have one that's lovely?)
- It's the perfect size. Small enough to fit into my purse and large enough for me to actually write in (and see what I've written).
- It has encouraging verse and quotes throughout. For example, on the cover: Jesus Christ the same yesterday, today, and forever. ~ Heb. 13:8 What a beautiful reminder whenever I pick up my planner!
- It has year, month, and week sections. Necessary for short-term and long-term planning.
- It offers additional sections for tasks, projects, info, and shopping (and a perforated shopping list section allows you to take the list with you).
- It also has easy tabs and is spiral bound.
- Oh, and it's very reasonably priced – did I mention that? (Much less expensive than what you find at your office supply store!)
Want to hear something else nice? I wrote Sue yesterday and asked if she'd consider giving all of us here at Club31Women a discount and she agreed! So not only is it reasonably priced, but you can get $2.00 off by using this coupon code when you check out: CLUB31200.
(She also offers quantity pricing and free shipping on orders over $49, if you want to get several for friends and sisters, or go in together with a group. That's what I did.)
You can learn more about the Homemaker's Friend Daily Planner HERE.
I don't know about you, but I'm actually getting excited about this coming new year. I've been very thankful for the last couple of weeks of holidays and celebrations, but I'm going to be ready for that fresh start!
Happy New Year, my friends!
*I shared a few of my own goals for the upcoming year and now I've love to hear some of yours! Do you have new resolutions and, if so, what are they?
In His grace,
*A small reminder, or if you're new here: I only recommend products that I actually use myself and genuinely love. I sometimes get a small commission for these, but this does not in any way affect your price. See my full disclosure.


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First Drives
Auto Shows
Spy Shots
Car Tech
Formula 1 is in the U.S. for the first time in five years this weekend, and it's already leading to the product tie-ins. No, we're not complaining. In this video you see the first footage of the Fiat 500 Abarth Cabrio, due to be unveiled at the 2012 Los Angeles Auto Show in just under two weeks... read more
As it looks to counter the effects of declining European sales, Fiat is turning an eye towards China. Still viewed as the world's largest automotive market, Fiat thinks... read more October 22, 2012 by Kurt Ernst
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Abarth, the performance division at Fiat, is out to show that even buyers of humble cars like the 500 minicar can enjoy the kinds of vehicle personalization that we're... read more September 18, 2012 by Viknesh Vijayenthiran
We've all been there. It starts innocently enough, perhaps with a drop-in, oiled-gauze air filter. The next thing you know, you're eating ramen to afford an ECU... read more September 14, 2012 by Kurt Ernst
Ever since we drove the 2012 Fiat 500 Abarth back in March, we've been fans of the peppy pint-sized pavement pounder. With 160 horsepower from its turbo 1.4-liter... read more September 10, 2012 by Nelson Ireson
When you're Jay Leno, taking delivery of the first or second customer car in country is generally as easy as picking up the phone and saying, "I'll need one... read more August 29, 2012 by Kurt Ernst
The Fiat 500 Turbo aims for the sweet spot between the relatively hardcore Abarth and the standard 500: More pep, less harshness. It does it all for a starting price of just... read more August 18, 2012 by Nelson Ireson
We knew it was coming, but now it's official; the 2013 Fiat 500 Turbo has made its debut today in the lead up to the Pebble Beach Concours and is set to launch this... read more August 17, 2012 by Viknesh Vijayenthiran
Last year, Jay Leno took delivery of the second Fiat 500 imported into the United States, and you'll soon get a chance to bid on that very same Prima Edizione car at an... read more July 27, 2012 by Kurt Ernst
While we here in the United States often complain that Europe gets better cars than we do, sometimes the opposite is true. In Europe, for example, the Fiat 500 Abarth comes... read more July 16, 2012 by Kurt Ernst
The Fiat 500L compact MPV unveiled at March's Geneva Motor Show won't be hitting showrooms until early next year but already we have the first image and details... read more July 5, 2012 by Viknesh Vijayenthiran
The 2013 Dodge Dart is one of the most eagerly anticipated models of the new model year—not just because it's the first model to be developed under pooled Fiat... read more June 28, 2012 by Bengt Halvorson
The idea of shoehorning a big engine into a small car is nothing new, and off the top of our collective heads we can name examples like the SHOgun, a Ford Fiesta infused with... read more June 25, 2012 by Kurt Ernst
If you're on the fence about buying a 2012 Fiat 500 Abarth hot hatch, we've got some bad news for you. Unless you can find a dealership with unsold inventory (and... read more June 5, 2012 by Kurt Ernst
There are few certainties in life, aside from death, taxes and the number one rule of automakers worldwide: future products are not to be commented on, ever. There's... read more June 4, 2012 by Kurt Ernst


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Identification of Binding Mode of a Platinum (II) Complex, PtCl2(DIP), and Calf Thymus DNA
Shahabadi, Nahid
Kashanian, Soheila
Fatahi, Azadeh
Bioinorganic Chemistry and Applications
The Pt(II) complex, PtCl2(DIP) (DIP = chelating dinitrogen ligand: 4,7-diphenyl-1,10-phenanthroline), was synthesized and characterized by elemental analysis (CHN) and 1H NMR and UV-vis techniques. The binding of this complex to calf thymus DNA was investigated using various physicochemical methods such as spectrophotometric, circular dichroism, spectrofluorometric, melting temperature, and viscosimetric techniques. Upon addition of the complex, important changes were observed in the characteristic UV-Vis bands (hyperchromism) of calf thymus DNA (CT-DNA): increase in melting temperature, sharp increase in specific viscosity of DNA, and induced CD spectral changes. Also the fluorescence spectral characteristics and interaction of Pt complex with DNA have been studied. Pt bound to DNA showed a marked decrease in the fluorescence intensity. The results show that both the complex and the NR molecules can intercalate competitively into the DNA double-helix structure. The experimental results show that the mode of binding of the this complex to DNA is classical intercalation.
Related Articles
Synthesis Characterization and DNA Interaction Studies of a New Zn(II) Complex Containing Different Dinitrogen Aromatic Ligands
Shahabadi, Nahid
Mohammadi, Somaye
Bioinorganic Chemistry and Applications
A mononuclear complex of Zn(II), [Zn(DIP)2 (DMP)] (NO3)2·2H2O in which DIP is 4,7-diphenyl-1,10-phenanthroline and DMP is 4,4′-dimethyl-2,2′-bipyridine has been prepared and characterized by 1HNMR spectroscopy, FT-IR, UV-Vis and elemental analysis techniques. DNA-binding properties of the complex were studied using UV-vis spectra, circular dichroism (CD) spectra, fluorescence, cyclic voltammetry (CV), and viscosity measurements. The results indicate that this zinc(II) complex can intercalate into the stacked base pairs of DNA and compete with the strong intercalator ethidium bromide for the intercalative binding sites.
Related Articles
DNA Interaction Studies of a New Platinum(II) Complex Containing Different Aromatic Dinitrogen Ligands
Shahabadi, Nahid
Mohammadi, Somaye
Alizadeh, Robabeh
Bioinorganic Chemistry and Applications
A new mononuclear Pt(II) complex, [Pt(DMP)(DIP)]Cl2.H2O, in which DMP is 4,4-dimethyl-2,2-bipyridine and DIP is 4,7-diphenyl-1,10-phenantroline, has been synthesized and characterized by physicochemical and spectroscopic methods. The binding interaction of this complex with calf thymus DNA (CT-DNA) was investigated using fluorimetry, spectrophotometry, circular dichroism, viscosimetry and cyclic voltametry (CV). UV-VIS spectrum showed 4 nm bathochromic shift of the absorption band at 280 nm along with significant hypochromicity for the absorption band of the complex. The intrnisic binding constant (Kb = 2 × 104 M−1) is more in keeping with intercalators and suggests this binding mode. The viscosity measurements showed that the complex-DNA interaction can be hydrophobic and confirm intercalation. Moreover, the complex induced detectable changes in the CD spectrum of CT-DNA. The fluorescence studies revealed that the probable quenching mechanism of fluorescence of the complex by CT-DNA is static quenching. The thermodynamic parameters (ΔH > 0 and ΔS > 0) showed that main interaction with hydrogenic forces occurred that is intercalation mode. Also, CV results confirm this mode because, with increasing the CT-DNA concentration, shift to higher potential was observed.
Related Articles
Targeting the endoplasmic reticulum with a membrane-interactive luminescent ruthenium(ii) polypyridyl complex† †Electronic supplementary information (ESI) available: Experimental details, characterization of 2 and Fig. S1–S6. See DOI: 10.1039/c3sc51725j Click here for additional data file.
Gill, Martin R.
Cecchin, Denis
Walker, Michael G.
Mulla, Raminder S.
Battaglia, Giuseppe
Smythe, Carl
Thomas, Jim A.
Chemical Science
The characterization and bioactivity of the dinuclear ruthenium(ii) complex [(Ru(DIP)2)2(tpphz)]4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j]phenazine) is reported.
The characterization and bioactivity of the dinuclear ruthenium(ii) complex [(Ru(DIP)2)2(tpphz)]4+ (DIP = 4,7-diphenyl-1,10-phenanthroline and tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′-j]phenazine) is reported. This new complex is found to be luminescent in acetonitrile, where excitation into MLCT (metal-to-ligand charge-transfer) bands in the visible area of the spectrum (λ ex = 450 nm, ε = 45 000 M–1 cm–1) result in red emission (λ em,max = 620 nm, Φ MLCT = 0.017). Aqueous in vitro binding studies indicate that this complex binds to duplex DNA with an affinity of 1.8 × 106 M–1 through a non-classical groove-binding interaction, however, unlike the parent complex [(Ru(phen)2)2(tpphz)]4+ (phen = 1,10-phenanthroline), it also displays an increase in MLCT luminescence on addition of liposomes. Confocal microscopy and TEM studies show that this lipophilic complex targets the endoplasmic reticulum of eukaryotic cells, where it functions as an imaging agent for this organelle, and cytotoxicity studies in human cancer cell lines indicate a comparable potency to the anti-cancer drug cisplatin.
Related Articles
Initial DNA Interactions of the Binuclear Threading Intercalator Λ,Λ-[μbidppz(bipy)4Ru2]4+: An NMR Study with [d(CGCGAATTCGCG)]2**
Wu, Lisha
Reymer, Anna
Persson, Cecilia
Kazimierczuk, Krzysztof
Brown, Tom
Lincoln, Per
Nordén, Bengt
Billeter, Martin
Chemistry (Weinheim an Der Bergstrasse, Germany)
Binuclear polypyridine ruthenium compounds have been shown to slowly intercalate into DNA, following a fast initial binding on the DNA surface. For these compounds, intercalation requires threading of a bulky substituent, containing one RuII, through the DNA base-pair stack, and the accompanying DNA duplex distortions are much more severe than with intercalation of mononuclear compounds. Structural understanding of the process of intercalation may greatly gain from a characterisation of the initial interactions between binuclear RuII compounds and DNA. We report a structural NMR study on the binuclear RuII intercalator Λ,Λ-B (Λ,Λ-[μ-bidppz(bipy)4Ru2]4+; bidppz=11,11′-bis(dipyrido[3,2-a:2′,3′-c]phenazinyl, bipy = 2,2′-bipyridine) mixed with the palindromic DNA [d(CGCGAATTCGCG)]2. Threading of Λ,Λ-B depends on the presence and length of AT stretches in the DNA. Therefore, the latter was selected to promote initial binding, but due to the short stretch of AT base pairs, final intercalation is prevented. Structural calculations provide a model for the interaction: Λ,Λ-B is trapped in a well-defined surface-bound state consisting of an eccentric minor-groove binding. Most of the interaction enthalpy originates from electrostatic and van der Waals contacts, whereas intermolecular hydrogen bonds may help to define a unique position of Λ,Λ-B. Molecular dynamics simulations show that this minor-groove binding mode is stable on a nanosecond scale. To the best of our knowledge, this is the first structural study by NMR spectroscopy on a binuclear Ru compound bound to DNA. In the calculated structure, one of the positively charged Ru2+ moieties is near the central AATT region; this is favourable in view of potential intercalation as observed by optical methods for DNA with longer AT stretches. Circular dichroism (CD) spectroscopy suggests that a similar binding geometry is formed in mixtures of Λ,Λ-B with natural calf thymus DNA. The present minor-groove binding mode is proposed to represent the initial surface interactions of binuclear RuII compounds prior to intercalation into AT-rich DNA.
DNA; intercalation; minor-groove binding; NMR spectroscopy; ruthenium
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The Paradoxical Thermodynamic Basis for the Interaction of Ethylene Glycol, Glycine, and Sarcosine Chains with Bovine Carbonic Anhydrase II
Krishnamurthy, Vijay M.
Bohall, Brooks R.
Semetey, Vincent
Whitesides, George M.
Journal of the American Chemical Society
This paper describes a systematic study of the thermodynamics of association of bovine carbonic anhydrase II (BCA) and para-substituted benzenesulfonamides with chains of oligoglycine, oligosarcosine, and oligoethylene glycol of lengths of 1-5 residues. For all three of these series of ligands, the enthalpy of binding became less favorable, and the entropy less unfavorable, as the chain length of the ligands increased. The dependence on chain length of the enthalpy was almost perfectly compensated by that of the entropy; this compensation resulted in dissociation constants that were independent of chain length for the three series of ligands. Changes in heat capacity were independent of chain length for the three series, and revealed that the amount of molecular surface area buried upon protein-ligand complexation did not increase with increasing chain length. Taken together, these data refute a model in which the chains of the ligands interact hydrophobically with the surface of BCA. To explain the data, a model is proposed based on decreasing "tightness" of the protein-ligand interface as the chain length of the ligand increases. This decreasing tightness, as chain length increases, is reflected in a less favorable enthalpy (due to fewer van der Waals contacts) and a less unfavorable entropy (due to greater mobility of the chain) of binding for ligands with long chains than for those with short chains. Thus, this study demonstrates a surprising example of enthalpy/entropy compensation in a well-defined system. Understanding this compensation is integral to the rational design of high-affinity ligands for proteins.
Related Articles
Luminescence of ruthenium(II) polypyridyls: evidence for intercalative binding to Z-DNA.
Friedman, A E
Kumar, C V
Turro, N J
Barton, J K
Nucleic Acids Research
Photophysical studies have been undertaken to characterize the binding interactions of enantiomers of Ru(phen)3(2+), Ru(DIP)3(2+), and racemic Ru(bpy)2dppz2+ (where phen = 1,10-phenanthroline, DIP = 4,7-diphenylphenanthroline, and dppz = dipyridophenazine) with Z-form poly d(GC). Parallel enhancements in steady state luminescent intensity and a lengthening of luminescent lifetimes are seen for ruthenium enantiomers with Z-DNA as for B-DNA but with enantioselectivities reversed. Greater enhancements are seen for delta-isomers with the right-handed helix but for lambda-isomers with the left-handed helix. Ru(bpy)2dppz2+, an avid intercalator in B-DNA, displays no luminescence free in aqueous solution, but luminesces brightly bound to either B- or Z-poly d(GC). Stern-Volmer quenching studies also support the enantioselective preference in binding to B-DNA by delta-isomers and a reversal with binding to Z-DNA preferentially by the lambda-isomers. Steady state polarization studies indicate a rigid association of the complexes with both B- and Z-DNA on the time-scale of their emission and again with symmetrical enantioselectivities for the left and right-handed helices. Given the well characterized intercalative association of the complexes with B-DNA, the parallel results seen here with Z-DNA point strongly to a comparable intercalative association with the Z-form helix. That molecules may interact with Z-DNA through intercalation has not been demonstrated previously and now requires consideration in describing the range of interactions of small molecules and proteins with Z-DNA.
Related Articles
Energetics of echinomycin binding to DNA
Leng, Fenfei
Chaires, Jonathan B.
Waring, Michael J.
Nucleic Acids Research
Differential scanning calorimetry and UV thermal denaturation have been used to determine a complete thermodynamic profile for the bis-intercalative interaction of the peptide antibiotic echinomycin with DNA. The new calorimetric data are consistent with all previously published binding data, and afford the most rigorous and direct determination of the binding enthalpy possible. For the association of echinomycin with DNA, we found ΔG° = –7.6 kcal mol–1, ΔH = +3.8 kcal mol–1 and ΔS = +38.9 cal mol–1 K–1 at 20°C. The binding reaction is clearly entropically driven, a hallmark of a process that is predominantly stabilized by hydrophobic interactions, though a deeper analysis of the free energy contributions suggests that direct molecular recognition between echinomycin and DNA, mediated by hydrogen bonding and van der Waals contacts, also plays an important role in stabilizing the complex.
Related Articles
Binding of Phenazinium Dye Safranin T to Polyriboadenylic Acid: Spectroscopic and Thermodynamic Study
Pradhan, Ankur Bikash
Haque, Lucy
Roy, Snigdha
Das, Suman
PLoS ONE
Here, we report results from experiments designed to explore the association of the phenazinium dye safranin T (ST, 3,7-diamino-2,8-dimethyl-5-phenylphenazinium chloride) with single and double stranded form of polyriboadenylic acid (hereafter poly-A) using several spectroscopic techniques. We demonstrate that the dye binds to single stranded polyriboadenylic acid (hereafter ss poly-A) with high affinity while it does not interact at all with the double stranded (ds) form of the polynucleotide. Fluorescence and absorption spectral studies reveal the molecular aspects of binding of ST to single stranded form of the polynucleotide. This observation is also supported by the circular dichroism study. Thermodynamic data obtained from temperature dependence of binding constant reveals that association is driven by negative enthalpy change and opposed by negative entropy change. Ferrocyanide quenching studies have shown intercalative binding of ST to ss poly-A. Experiments on viscosity measurements confirm the binding mode of the dye to be intercalative. The effect of [Na+] ion concentration on the binding process suggests the role of electrostatic forces in the complexation. Present studies reveal the utility of the dye in probing nucleic acid structure.
Related Articles
Study on the Interaction between Isatin-β-Thiosemicarbazone and Calf Thymus DNA by Spectroscopic Techniques
Pakravan, Parvaneh
Masoudian, Shahla
Iranian Journal of Pharmaceutical Research : IJPR
The interaction between isatin-β-thiosemicarbazone (IBT) and calf thymus DNA (CT-DNA) was investigated in physiological buffer (pH 7.4) using Neutral Red (NR) dye as a spectral probe by UV–Vis absorption and fluorescence spectroscopy, as well as viscosity measurements. The IBT is stabilized by intercalation in the DNA (K [IBT –DNA] = 1.03×105 M−1), and displaces the NR dye from the NR–DNA complex. The binding constants Kf and number of binding sites (n≈1) of IBT with DNA were obtained by fluorescence quenching method at different temperatures. Furthermore, the enthalpy and entropy of the reaction between IBT and CT-DNA showed that the reaction is enthalpy-favored and entropy-disfavored. The changes in the base stacking of CT-DNA upon the binding of IBT are reflected in the circular dichroic (CD) spectral studies. The viscosity increase of CT-DNA solution is another evidence to indicate that, IBT is able to be intercalated in the DNA base pairs.
CT-DNA; Isatin-β-thiosemicarbazone; Neutral Red dye; Intercalation
Related Articles
DNA Binding and Photocleavage Studies of Cobalt(III) Polypyridine Complexes: [Co(en)2PIP]3+, [Co(en)2IP]3+, and [Co(en)2phen-dione]3+
Nagababu, Penumaka
Satyanarayana, S.
Bioinorganic Chemistry and Applications
In this paper, three complexes of type [Co(en)2PIP]3+(PIP=2-phenylimidazo[4,5-f][1,10,] phenanthroline)(1), [Co(en)2IP]3+ (IP = imidazo[4,5-f][1,10,] phenanthroline)(2), and [Co(en)2phen-dione]3+(1,10 phenanthroline 5,6,dione)(3) have been synthesized and characterized by UV/VIS, IR, 1H NMR spectral methods. Absorption spectroscopy, emission spectroscopy, viscosity measurements, and DNA melting techniques have been used for investigating the binding of these two complexes with calf thymus DNA, and photocleavage studies were used for investigating these binding of these complexes with plasmid DNA. The spectroscopic studies together with viscosity measurements and DNA melting studies support that complexes 1 and 2 bind to CT DNA (= calf thymus DNA) by intercalation mode via IP or PIP into the base pairs of DNA, and complex 3 is binding as groove mode. Complex 1 binds more avidly to CT DNA than 2 and 3 which is consistent with the extended planar ring π system of PIP. Noticeably, the two complexes have been found to be efficient photosensitisers for strand scissions in plasmid DNA.
Related Articles
Protein-Ligand Interactions: Thermodynamic Effects Associated with Increasing Nonpolar Surface Area
Myslinski, James M.
DeLorbe, John E.
Clements, John H.
Martin, Stephen F.
Journal of the American Chemical Society
Thermodynamic parameters were determined for complex formation between the Grb2 SH2 domain and Ac–pTyr–Xaa–Asn derived tripeptides in which the Xaa residue is an α,α-cycloaliphatic amino acid that varies in ring size from 3- to 7-membered. Although the 6- and 7-membered ring analogs are approximately equipotent, binding affinities of those having 3- to 6-membered rings increase incrementally with ring size because increasingly more favorable binding enthalpies dominate increasingly unfavorable binding entropies, a finding consistent with an enthalpy-driven hydrophobic effect. Crystallographic analysis reveals that the only significant differences in structures of the complexes are in the number of van der Waals contacts between the domain and the methylene groups in the Xaa residues. There is a positive correlation between buried nonpolar surface area and binding free energy and enthalpy, but not with ΔCp. Displacing a water molecule from a protein-ligand interface is not necessarily reflected in a favorable change in binding entropy. These findings highlight some of the fallibilities associated with commonly held views of relationships of structure and energetics in protein-ligand interactions and have significant implications for ligand design.
Related Articles
Mechanistic Insights into Phosphoprotein-Binding FHA Domains
Accounts of chemical research
FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is: how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure.
Although FHA domains share sequence identity at only five loop residues, they all fold into a β-sandwich of two β-sheets. The conserved Arg and Ser of the recognition loops recognize the phosphorylation of the Thr targeted. Side chains emanating from loops that join β-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphoThr in sequence (pT+3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT+3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged, polar side chains at pT+3. However, another FHA domain instead chooses on the basis of pT−2, pT−3, and pT+1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a β-strand to its β-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family of FHA domains by a bioinformatics approach.
The phosphopeptide-dependent dynamics of an FHA domain, SH2 domain, and PTB domain suggest a common theme: rigid, preformed binding surfaces support van der Waals contacts that provide favorable binding enthalpy. Despite the lack of pronounced conformational changes in FHA domains linked to binding events, more subtle adjustments may be possible. In the one FHA domain tested, phosphoThr peptide binding is accompanied by increased flexibility just outside the binding site and increased rigidity across the β-sandwich. The folding of the same FHA domain progresses through near-native intermediates that stabilize the recognition loops in the center of the phosphoprotein-binding surface; this may promote rigidity in the interface and affinity for targets phosphorylated on threonine.
FHA domain; phosphorylation-dependent signaling; protein structure; molecular recognition; protein dynamics; protein folding
Related Articles
The Effects of Extending of Co-planarity in a Series of Structurally Relative Polypyridyl Palladium(II) Complexes on DNA-binding and Cytotoxicity Properties
Shahraki, Somaye
Mansouri-Torshizi, Hassan
Sori Nezami, Ziba
Ghahghaei, Arezou
Yaghoubi, Fatemeh
Divsalar, Adeleh
Saboury, Ali-Akbar
H. Shirazi, Farshad
Iranian Journal of Pharmaceutical Research : IJPR
In depth interaction studies between calf thymus deoxyribonucleic acid (CT-DNA) and a series of four structurally relative palladium(II) complexes [Pd(en)(HB)](NO3)2 (a-d), where en is ethylenediamine and heterocyclic base (HB) is 2,2'-bipyridine (bpy, a); 1,10-phenanthroline (phen, b); dipyridoquinoxaline (dpq, c) and dipyridophenazine (dppz, d) (Figure 1), were performed. These studies have been investigated by utilizing the electronic absorption spectroscopy, fluorescence spectra and ethidium bromide (EBr) displacement and gel filtration techniques. a-d complexes cooperatively bind and denature the DNA at low concentrations. Their concentration at midpoint of transition, L1/2, follows the order a >> b > c > d. Also the g, the number of binding sites per 1000 nucleotides, follows the order a >> b ~ c > d. EBr and Scatchard experiments for a-d complexes suggest efficient intercalative binding affinity to CT-DNA giving the order: d > c > b > a. Several binding and thermodynamic parameters are also described. The biological activity of these cationic and water soluble palladium complexes were tested against chronic myelogenous leukemia cell line, K562. b, c and d complexes show cytotoxic concentration (Cc50) values much lower than cisplatin.
Pd(II) complexes; Cytotoxicity; DNA binding
Related Articles
Intercalative and nonintercalative binding of large cationic porphyrin ligands to calf thymus DNA.
Carvlin, M J
Fiel, R J
Nucleic Acids Research
The large meso-substituted porphine, meso-tetra(4-N-methylpyridyl)porphine has been identified as a DNA-interactive ligand with a capacity for intercalation (1,2). Subsequently, the 2-N-methyl, 3-N-methyl and N-trimethylanilinium analogues of this porphyrin intercalator have been obtained for physico-chemical analyses (absorption spectroscopy, viscometry, circular dichroism, unwinding of supercoiled DNA). In this paper we discuss the factors affecting the character of porphyrin binding (intercalative, as is the case for the 4-N-methyl and 3-N-methyl porphines, versus non-intercalative, as is the case for the 2-N-methyl and N-trimethylanilinium porphines) and the impact that porphyrins' binding has upon the structure of DNA. The molecular conformation of the porphyrin ligand varies slightly within this series so that the ability of a given porphyrin to intercalate may be correlated with the arrangement of charged groups, the planarity of the porphine ring and the effective width of the individual molecules. The results from these studies indicate that sequence selective binding occurs within a small aperture of solution conditions.
Related Articles
Investigation of Atomic Level Patterns in Protein—Small Ligand Interactions
Chen, Ke
Kurgan, Lukasz
PLoS ONE
Shape complementarity and non-covalent interactions are believed to drive protein-ligand interaction. To date protein-protein, protein-DNA, and protein-RNA interactions were systematically investigated, which is in contrast to interactions with small ligands. We investigate the role of covalent and non-covalent bonds in protein-small ligand interactions using a comprehensive dataset of 2,320 complexes.
Methodology and Principal Findings
We show that protein-ligand interactions are governed by different forces for different ligand types, i.e., protein-organic compound interactions are governed by hydrogen bonds, van der Waals contacts, and covalent bonds; protein-metal ion interactions are dominated by electrostatic force and coordination bonds; protein-anion interactions are established with electrostatic force, hydrogen bonds, and van der Waals contacts; and protein-inorganic cluster interactions are driven by coordination bonds. We extracted several frequently occurring atomic-level patterns concerning these interactions. For instance, 73% of investigated covalent bonds were summarized with just three patterns in which bonds are formed between thiol of Cys and carbon or sulfur atoms of ligands, and nitrogen of Lys and carbon of ligands. Similar patterns were found for the coordination bonds. Hydrogen bonds occur in 67% of protein-organic compound complexes and 66% of them are formed between NH- group of protein residues and oxygen atom of ligands. We quantify relative abundance of specific interaction types and discuss their characteristic features. The extracted protein-organic compound patterns are shown to complement and improve a geometric approach for prediction of binding sites.
Conclusions and Significance
We show that for a given type (group) of ligands and type of the interaction force, majority of protein-ligand interactions are repetitive and could be summarized with several simple atomic-level patterns. We summarize and analyze 10 frequently occurring interaction patterns that cover 56% of all considered complexes and we show a practical application for the patterns that concerns interactions with organic compounds.
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Microwave synthesis of mixed ligand diimine–thiosemicarbazone complexes of ruthenium(ii): biophysical reactivity and cytotoxicity†
Beckford, Floyd A.
Shaloski, Michael
Leblanc, Gabriel
Thessing, Jeffrey
Lewis-Alleyne, Lesley C.
Holder, Alvin A.
Li, Liya
Seeram, Navindra P.
Dalton transactions (Cambridge, England : 2003)
A novel microwave-assisted synthetic method has been used to synthesise a series of mixed ligand ruthenium(ii) compounds containing diimine as well as bidentate thiosemicarbazone ligands. The compounds contain the diimine 1,10-phenanthroline (phen) or 2,2′-bipyridine (bpy) and the thiosemicarbazone is derived from 9-anthraldehyde. Based on elemental analyses and spectroscopic data, the compounds are best formulated as [(phen)2Ru(thiosemicarbazone)](PF6)2 and [(phen)2Ru(thiosemicarbazone)](PF6)2 where thiosemicarbazone = 9-anthraldehydethiosemicarbazone, 9-anthraldehyde-N(4)-methylthiosemicarbazone, and 9-anthraldehyde-N(4)-ethylthiosemicarbazone. Fluorescence competition studies with ethidium bromide, along with viscometric measurements suggests that the complexes bind calf thymus DNA (CTDNA) relatively strongly via an intercalative mode possibly involving the aromatic rings of the diimine ligands. The complexes show good cytotoxic profiles against MCF-7 and MDA-MB-231 (breast adenocarcinoma) as well as HCT 116 and HT-29 (colorectal carcinoma) cell lines.
Related Articles
Structural analysis of DNA complexation with cationic lipids
Marty, Regis
N'soukpoé-Kossi, Christophe N.
Charbonneau, David
Weinert, Carl Maximilian
Kreplak, Laurent
Tajmir-Riahi, Heidar-Ali
Nucleic Acids Research
Complexes of cationic liposomes with DNA are promising tools to deliver genetic information into cells for gene therapy and vaccines. Electrostatic interaction is thought to be the major force in lipid–DNA interaction, while lipid-base binding and the stability of cationic lipid–DNA complexes have been the subject of more debate in recent years. The aim of this study was to examine the complexation of calf-thymus DNA with cholesterol (Chol), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), dioctadecyldimethylammoniumbromide (DDAB) and dioleoylphosphatidylethanolamine (DOPE), at physiological condition, using constant DNA concentration and various lipid contents. Fourier transform infrared (FTIR), UV-visible, circular dichroism spectroscopic methods and atomic force microscopy were used to analyse lipid-binding site, the binding constant and the effects of lipid interaction on DNA stability and conformation. Structural analysis showed a strong lipid–DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of KChol = 1.4 (±0.5) × 104 M−1, KDDAB = 2.4 (±0.80) × 104 M−1, KDOTAP = 3.1 (±0.90) × 104 M−1 and KDOPE = 1.45 (± 0.60) × 104 M−1. The order of stability of lipid–DNA complexation is DOTAP>DDAB>DOPE>Chol. Hydrophobic interactions between lipid aliphatic tails and DNA were observed. Chol and DOPE induced a partial B to A-DNA conformational transition, while a partial B to C-DNA alteration occurred for DDAB and DOTAP at high lipid concentrations. DNA aggregation was observed at high lipid content.
Related Articles
Interaction of 6 Mercaptopurine with Calf Thymus DNA – Deciphering the Binding Mode and Photoinduced DNA Damage
Rehman, Sayeed Ur
Yaseen, Zahid
Husain, Mohammed Amir
Sarwar, Tarique
Ishqi, Hassan Mubarak
Tabish, Mohammad
PLoS ONE
DNA is one of the major intracellular targets for a wide range of anticancer and antibiotic drugs. Elucidating the binding between small molecules and DNA provides great help in understanding drug-DNA interactions and in designing of new and promising drugs for clinical use. The ability of small molecules to bind and interfere with DNA replication and transcription provides further insight into how the drugs control the expression of genes. Interaction of an antimetabolite anticancer drug 6mercaptopurine (6MP) with calf thymus DNA was studied using various approaches like UV-visible spectroscopy, fluorescence spectroscopy, CD, viscosity and molecular docking. UV-visible spectroscopy confirmed 6MP-DNA interaction. Steady state fluorescence experiments revealed a moderate binding constant of 7.48×103 M−1 which was consistent with an external binding mode. Competitive displacement assays further confirmed a non-intercalative binding mode of 6MP which was further confirmed by CD and viscosity experiments. Molecular docking further revealed the minimum energy conformation (−119.67 kJ/mole) of the complex formed between DNA and 6MP. Hence, the biophysical techniques and in-silico molecular docking approaches confirmed the groove binding/electrostatic mode of interaction between 6MP and DNA. Further, photo induced generation of ROS by 6MP was studied spectrophotometrically and DNA damage was assessed by plasmid nicking and comet assay. There was a significant increase in ROS generation and consequent DNA damage in the presence of light.
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Multifaceted interplay between lipophilicity, protein interaction and luminescence parameters of non-intercalative ruthenium(II) polypyridyl complexes controlling cellular imaging and cytotoxic properties
Mazuryk, Olga
Magiera, Katarzyna
Rys, Barbara
Suzenet, Franck
Kieda, Claudine
Brindell, Małgorzata
Journal of Biological Inorganic Chemistry
Here, we examine the photophysical properties of five ruthenium(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and functionalized bipyridine (R1bpy-R2, where R1 = H or CH3, R2 = H, CH3, COO−,4-[3-(2-nitro-1H-imidazol-1-yl)propyl] or 1,3-dicyclohexyl-1-carbonyl-urea) towards development of luminescence probes for cellular imaging. These complexes have been shown to interact with albumin and the formed adducts exhibited up to eightfold increase in the luminescence quantum yield as well as the average lifetime of emission. It was demonstrated that they cannot bind to DNA through the intercalation mode and its luminescence in the presence of DNA is quenching. Cell viability experiments indicated that all complexes possess significant dose-dependent cytotoxicity (with IC50 5–19 μM) on 4T1 breast cancer cell line and their anti-proliferative activity correlates very well with their lipophilicity. Cellular uptake was studied by measuring the ruthenium content in cells using ICP-MS technique. As expected, the better uptake is directly related to higher lipophilicity of doubly charged ruthenium complexes while uptake of monocationic one is much lower in spite of the highest lipophilicity. Additionally staining properties were assessed using flow cytometry and fluorescence microscopy. These experiments showed that complex with 1,3-dicyclohexyl-1-carbonyl-urea substituent exhibits the best staining properties in spite of the lowest luminescence quantum yield in buffered solution (pH 7.4). Our results point out that both the imaging and cytotoxic properties of the studied ruthenium complexes are strongly influence by the level of internalization and protein interaction.
Electronic supplementary material
The online version of this article (doi:10.1007/s00775-014-1187-5) contains supplementary material, which is available to authorized users.
Ruthenium polypyridyl complexes; Cytotoxicity; Optical imaging; Luminescence; Protein binding
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Synthesis and Characterisation of Copper(II) Complexes with Tridentate NNO Functionalized Ligand: Density Function Theory Study, DNA Binding Mechanism, Optical Properties, and Biological Application
Hazra, Madhumita
Dolai, Tanushree
Pandey, Akhil
Dey, Subrata Kumar
Patra, Animesh
Bioinorganic Chemistry and Applications
The photo physical properties of two mononuclear pentacoordinated copper(II) complexes formulated as [Cu(L)(Cl)(H2O)] (1) and [Cu(L)(Br)(H2O)] (2) HL = (1-[(3-methyl-pyridine-2-ylimino)-methyl]-naphthalen-2-ol) were synthesized and characterized by elemental, physicochemical, and spectroscopic methods. The density function theory calculations are used to investigate the electronic structures and the electronic properties of ligand and complex. The interactions of copper(II) complexes towards calf thymus DNA were examined with the help of absorption, viscosity, and fluorescence spectroscopic techniques at pH 7.40. All spectroscopy's result indicates that complexes show good binding activity to calf thymus DNA through groove binding. The optical absorption and fluorescence emission properties of microwires were characterized by fluorescence microscope. From a spectroscopic viewpoint, all compounds strongly emit green light in the solid state. The microscopy investigation suggested that microwires exhibited optical waveguide behaviour which are applicable as fluorescent nanomaterials and can be used as building blocks for miniaturized photonic devices. Antibacterial study reveals that complexes are better antimicrobial agents than free Schiff base due to bacterial cell penetration by chelation. Moreover, the antioxidant study of the ligand and complexes is evaluated by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assays, which demonstrate that the complexes are of higher antioxidant activity than free ligand.
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Cytotoxic Activities and DNA Binding Properties of 1-Methyl-7H-indeno[1,2-b]Quinolinium-7-(4-dimethylamino) Benzylidene Triflate
Li, Wen
Ji, Yuan Yuan
Wang, Jian Wen
Zhu, Yong Ming
DNA and Cell Biology
The interaction of calf thymus DNA (ct-DNA) with a novel synthesized pyrazolo[1,5-a]indole compound 1-methyl-7H-indeno[1,2-b]quinolinium-7-(4-dimethylamino) benzylidene triflate (MIDBT) was extensively studied by various spectroscopic techniques, viscosity measurements, and gel electrophoresis. The UV-visible observation implied that the compound interacted with ct-DNA by two binding modes, intercalating into the DNA base pairs and attaching to the helix exterior of DNA. The results of the fluorescent quenching and viscosity measurements showed that MIDBT could intercalate into DNA base pairs deeply in a classical intercalative mode. Circular dichroism results showed that the binding of MIDBT shifted ct-DNA conformation from B to A at low concentrations. In the gel electrophoresis, the compound was found to promote the cleavage of plasmid pBR 322 DNA effectively. Furthermore, cytotoxic studies of this compound against eleven selected tumor cell lines have been done. The values of 50% cytotoxic concentration (IC50) were in the range of 1.09–18.84 μM, exhibiting the potent cytotoxic properties.
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Disturbance of DNA conformation by the binding of testosterone-based platinum drugs via groove-face and intercalative interactions: a molecular dynamics simulation study
Cui, Shanshan
Wang, Yan
Chen, Guangju
BMC Structural Biology
To explore novel platinum-based anticancer agents that are distinct from the structure and interaction mode of the traditional cisplatin by forming the bifunctional intrastrand 1,2 GpG adduct, the monofunctional platinum + DNA adducts with extensive non-covalent interactions had been studied. It was reported that the monofunctional testosterone-based platinum(II) agents present the high anticancer activity. Moreover, it was also found that the testosterone-based platinum agents could cause the DNA helix to undergo significant unwinding and bending over the non-testosterone-based platinum agents. However, the interaction mechanisms of these platinum agents with DNA at the atomic level are not yet clear so far.
In the present work, we used molecular dynamics (MD) simulations and DNA conformational dynamics calculations to study the DNA distortion properties of the testosterone-based platinum + DNA, the improved testosterone-based platinum + DNA and the non-testosterone-based platinum + DNA adducts. The results show that the intercalative interaction of the improved flexible testosterone-based platinum agent with DNA molecule could cause larger DNA conformational distortion than the groove-face interaction of the rigid testosterone-based platinum agent with DNA molecule. Further investigations for the non-testosterone-based platinum agent reveal the occurrence of insignificant change of DNA conformation due to the absence of testosterone ligand in such agent. Based on the DNA dynamics analysis, the DNA base motions relating to DNA groove parameter changes and hydrogen bond destruction of DNA base pairs were also discussed in this work.
The flexible linker in the improved testosterone-based platinum agent causes an intercalative interaction with DNA in the improved testosterone-based platinum + DNA adduct, which is different from the groove-face interaction caused by a rigid linker in the testosterone-based platinum agent. The present investigations provide useful information of DNA conformation affected by a testosterone-based platinum complex at the atomic level.
Molecular dynamics simulations; Groove-face and intercalative interactions; Testosterone-based platinum agent; Pt + DNA adducts; DNA conformation distortion
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Spectroscopic investigations on the interactions of potent platinum(II) anticancer agents with bovine serum albumin
Krause-Heuer, Anwen M.
Price, William S.
Aldrich-Wright, Janice R.
Journal of Chemical Biology
The interactions of three platinum(II)-based anticancer complexes [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)]2+, [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)]2+, and [(5,6-dimethyl-1,10-phenanthroline)(1,2-diaminoethane)platinum(II)]2+ (56MEEN) with BSA have been examined by circular dichroism (CD), fluorescence and 1H pulsed gradient spin–echo (PGSE) diffusion NMR spectroscopy. The number of association constants and sites differed depending upon the spectroscopic method. This may be because each technique monitors different types of interaction/s and/or as a consequence of the different concentration ranges required for each technique. The titration of BSA with the achiral 56MEEN as monitored by CD indicates a reduction in the α-helical nature of the albumin, with the association constant calculated to be ~5 × 106 M−1 for one site. Due to the chiral nature of the other two complexes, their association with albumin was not monitored using CD but was examined using fluorescence and PGSE diffusion NMR. Titration of BSA with any of the three metal complexes resulted in quenching of fluorescence, with the number of association sites calculated to be ~1.1, with an association constant of ~2 × 105 M−1. PGSE diffusion NMR provided insights into interactions occurring with the BSA in its entirety, rather than with individual regions. Metal complex binding sites were estimated (~10 equivalent) from the diffusion data, with the average association constant for all sites ~102–103M−1. These experiments highlight the information that can be elucidated from complementary spectroscopic techniques and demonstrate the usefulness of PGSE diffusion NMR in monitoring multiple weak binding sites, which is of great importance in studying drug-biomolecule interactions.
Electronic supplementary material
The online version of this article (doi:10.1007/s12154-012-0074-1) contains supplementary material, which is available to authorized users.
Platinum; PGSE NMR; Intercalator; Albumin; Binding; Diffusion; Spectroscopy
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Interaction of berenil with the tyrT DNA sequence studied by footprinting and molecular modelling. Implications for the design of sequence-specific DNA recognition agents.
Laughton, C A
Jenkins, T C
Fox, K R
Neidle, S
Nucleic Acids Research
We have developed a technique of partially-restrained molecular mechanics enthalpy minimisation which enables the sequence-dependence of the DNA binding of a non-intercalating ligand to be studied for arbitrary sequences of considerable length (greater than = 60 base-pairs). The technique has been applied to analyse the binding of berenil to the minor groove of a 60 base-pair sequence derived from the tyrT promoter; the results are compared with those obtained by DNAse I and hydroxyl radical footprinting on the same sequence. The calculated and experimentally observed patterns of binding are in good agreement. Analysis of the modelling data highlights the importance of DNA flexibility in ligand binding. Further, the electrostatic component of the interaction tends to favour binding to AT-rich regions, whilst the van der Waals interaction energy term favours GC-rich ones. The results also suggest that an important contribution to the observed preference for binding in AT-rich regions arises from lower DNA perturbation energies and is not accompanied by reduced DNA structural perturbations in such sequences. It is therefore concluded that those modes of DNA distortion favourable to binding are probably more flexible in AT-rich regions. The structure of the modelled DNA sequence has also been analysed in terms of helical parameters. For the DNA energy-minimised in the absence of berenil, certain helical parameters show marked sequence-dependence. For example, purine-pyrimidine (R-Y) base pairs show a consistent positive buckle whereas this feature is consistently negative for Y-R pairs. Further, CG steps show lower than average values of slide while GC steps show lower than average values of rise. Similar analysis of the modelling data from the calculations including berenil highlights the importance of DNA flexibility in ligand binding. We observe that the binding of berenil induces characteristic responses in different helical parameters for the base-pairs around the binding site. For example, buckle and tilt tend to become more negative to the 5'-side of the binding site and more positive to the 3'-side, while the base steps at either side of the centre of the site show increased twist and decreased roll.
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Plastic fluteboard
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Plastic fluteboard is very much like corrugated cardboard, but made from plastic. It can be found at sign companies that print custom signs like for the politicians. Large sheets can be found at plastic dealers. Coroplast is one brand name. It is not hard to find, but will not likely be at your local big-box home improvement store. Note that using this material, is much harder to make a solar cooker that will fold down compactly than when constructing with cardboard.
One way to address the folding problem is with the use of plastic zip-ties. The Panel-Box Cooker uses the zip-ties to create hinge connections for the panels. Fluteboard can be creased and folded, but it does not offer the ability to have the articulated panels lay flat for storage or shipping of the cooker.
External links
- University students put corrugated plastic to the test - Solar Cooker Review
- http://www.coroplast.com
- Coruplas and Coruprint twin-wall polypropylene information available in South Africa.


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Posts Tagged with "Charlotte Olympia"
Charlotte Olympia Perfume Bottle Clutch is so interesting…
Charlotte Olympia Paris Perfume Bottle Clutch is so interesting…inspired by Paris this perspex clutch is a little odd and a little bit kitschy cool at the same time. Ask me if I want one? In some ways I do…do I want it more now that it is on sale for 40% off ? You betcha – I like it better now on sale than regular price.
What would you do with this perspex clutch this summer? I guess you can use it to stash your mini perfume and lipstick plus some emergency money in it for a night out on the town or for a summer party on Long Island on the North Shore this summer?
Get the Charlotte Olympia Paris Perfume Bottle clutch now for 40% off.
CHARLOTTE OLYMPIA Leading Lady glitter-finished sandals
CHARLOTTE OLYMPIA Leading Lady glitter-finished sandals – you know you want these. Here is why – they are 6 inch platform heels, they glitter, they have jewels on them, and they are sexy as hell. Why you ask? Well you have a wedding to go to in England this summer or in Asia and you need them to go with your Oscar de la Renta lace black dress. Yep you know that I know that you have been eyeing that black dress by Oscar de la Renta and that you will end up buying it to go with these heels, so get the heels now, and get the dress in a week or so and you are all set to look prettier than the bride. At least you are not in the wedding so you won't have to worry about her making you look terrible in a chartreuse colored ruffled nightmare of a bridesmaid dress. Rejoice.
Charlotte Olympia glitter leading lady glitter finished sandals are $945.
Charlotte Olympia and Golden Globes are Fashions Most Talked about Trends at the Moment
Shopping and Goodies is featuring the latest trends and you'll love them. We're sharing Charlotte Olympia's latest (craziest) platforms, gorgeous blush colored gowns, stunning emerald jewelry (for less) and must-have leather skinnies for spring. If you've packed on the pounds this holiday you'll definitely want to see how to conquer all that holiday binging! Find out what celebs love toughing it out in sky-high heels.They're not alone…we all do that! I'd start reading what the chicest fashionistas have to say. We always have the latest fashion tips and styles.
A Few Goody Gumdrops asks has success gone to Charlotte Olympia's feet?
Be Voguish features the stars who stunned the Golden Globes red carpet in BLUSH.
The Fashionable Housewife show us how to get in shape after holiday binging!
The Find shows you how to get the emerald jewelry look for less!
Girls Talkin Smack shares five celebs who love wearing heels!
Shopping and Info is loving DL1961′s Hazel Black Leather pants for spring!


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"Great Podcast!Dear Allie & John, We've been in the lifestyle for almost a decade now. It seems we all in the lifestyle share the same experiences. We love to listen and it makes us smile more often than not to hear that you were in a very similar situation like us or that you had the same thoughts and fears... Keep up the good work!" -- angel6devil8
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Endo (24 Lyrics)
Endo was a four-piece nu metal music group from Miami, Florida. The band formed in 1995 with Lou Orenstein, Diego Ponsa, Reggie Barret, Steve Morris and Gil Bitton. A local production company, "Concre [more..]
No More Make Up
by Mammuth (Shine)
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On LyricsInfo.org you can find lyrics, album names, artist overviews, history, current and past members of bands, listen and watch videos.


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