a halogen bond ( xb ) 
 is the close to linear , noncovalent interaction 
 between an electron poor region of a halogen and an electron donor . the chemical nature of the interaction was first 
 rationalized by introduction of the -hole concept , followed by description of the impact of charge - transfer , 
 dispersion , polarization , and electrostatic forces . over the past decade , halogen bonds have been increasingly applied 
 in a variety of research disciplines including material sciences , 
 crystal engineering , structural biology , anion recognition and transportation , 
 medicinal chemistry , organic synthesis , and organocatalysis . halogen bonding was recently utilized in the development of ionic 
 liquid crystals , in multidentate anion 
 receptors , and in the enantioselective recognition of chiral anions . it was demonstrated to be applicable as noncovalent 
 activator in organocatalysis , and as 
 a new tool in drug discovery . it found application 
 in the development of luminescent and phosphorescent optoelectronics , and of functional materials . halogen bonding has the potential to become a chemical tool as widely 
 applicable as hydrogen bonding . [ bis(pyridine)halogen ] complexes and their substituted 
 analogues encompass a reactive halogen(i ) species that is stabilized 
 by two electron donors in an [ n  x  n ] halogen 
 bond . both bromine(i ) and iodine(i ) containing complexes are useful 
 reagents in organic synthesis , for example for electrophilic halogenation 
 of alkenes , alkynes and aromatics , and for oxidations . in three - center - four - electron n ] halogen 
 bonds , the halogen is stabilized by simultaneous 
 coordination to two nitrogen electron donors . the three atoms of the 
 [ n  x  n ] system may either form a static , 
 symmetric geometry , [ nxn ] , or two asymmetric structures in a rapid equilibrium , [ n  xn ]  [ nx  n ] , the latter being analogous to the tautomeric exchange typical of 
 related [ n  h geometry , the halogen forms two equally long and strong nx 
 bonds , and its motion between the two nitrogens is described by a 
 single - well energy potential . in contrast , in the asymmetric , dynamic 
 system , in each asymmetric isomer the halogen forms one shorter and 
 stronger covalent n  x bond , and one longer and weaker nx 
 halogen bond . as the halogen jumps between the two nitrogens , its 
 motion is described by a double - well energy potential . the centrosymmetric [ n  x  n ] halogen bonds 
 are particularly strong , their strength being similar 
 to that of the halogen bond of the isoelectronic [ i  i  i ] . we have previously shown 
 that the [ n  i  n ] halogen bonds of [ bis(pyridine)iodine ] ( 1a , figure 1 ) and [ 1,2-bis((pyridine-2-ylethynyl)benzene)iodine ] ( 2a ) complexes are exceptionally strong , and 
 that their geometry is static symmetric in solution , independent of the nature of the counterion present . [ bis(4-r - pyridine)iodine ] bf4 ( 1a  g ) , and geometrically 
 restrained 
 [ 1,2-bis((4-r - pyridine-2-ylethynyl)benzene)iodine ] bf4 ( 2a  g ) were used as model systems for evaluation of the influence of electron 
 density alteration on the [ n  i  n ] halogen 
 bond . n ] halogen bond was achieved by variation of the r - substituents , 
 resulting in complexes with an increasing electron density in the 
 order no2 < cf3 < h < i distances for the most favorable interaction , 
 whereas the 1,2-diethynylbenzene backbone of 2 inhibits 
 rotation around the n d and their monodeuterated isotopologs 2a  d - d were used in ipe nmr experiments 
 for determining the geometry of their [ n  i  n ] halogen bonds . the influence of electron 
 density alteration on the strength and 
 geometry of the three - center - four - electron [ n  x  n ] halogen bond has so far not been assessed . a decreased electron 
 donating ability of the nitrogens , as induced by electron withdrawing 
 substituents , can be expected to destabilize the symmetric [ n  i if the central iodine(i ) is unable to efficiently accept electrons 
 into its empty p - orbital from two electron poor nitrogens simultaneously , 
 it may prefer to compensate its electron depletion by forming a covalent 
 bond to one of the nitrogens , instead of forming halogen bonds to 
 both . in contrast , an increased electron density , induced 
 by electron donating substituents , is expected to stabilize the symmetric 
 [ nin ] geometry by 
 strengthening the two ni halogen bonds . this is 
 expected to decrease the reactivity of the complex . in this 
 study , we report our findings , from systematic solution 
 nmr , x - ray diffraction , reaction kinetics , and computational investigations 
 on the influence of electron density alterations on [ an understanding of electronic 
 effects is , above all , expected to provide a useful handle for the 
 modulation of the reactivity of [ bis(pyridine)halogen]-type reagents . [ bis(pyridine)halogen ] complexes and their geometrically 
 restrained [ 1,2-bis((pyridin-2-ylethynyl)benzene)halogen ] analogues are the model systems typically used to gain understanding 
 of the [ n  x  n ] halogen bond . in this study , we introduce substituents of varying 
 electronic properties in the para - positions relative 
 to the pyridine nitrogens ( figure 1 ) , to study the influence of electron density alteration 
 on the strength and geometry of their [ n  i  n ] halogen bond . the 4-substituted electron rich [ bis(pyridine)iodine ] bf4 complexes 1b ( 4-me ) , 1c ( 4-ome ) , and 1d ( 4-nme2 ) as well as their electron poor analogue 1f ( 4-cf3 ) , ( figure 1 ) were synthesized from their corresponding ag complexes 
 by addition of molecular i2 , following our previously reported 
 protocol toward 1a . complex 1b ( 4-me ) rapidly decomposed upon isolation . the 4-substituted [ 1,2-bis((pyridine-2-ylethynyl)benzene)iodine ] bf4 complexes 2a ( 4-h ) , 2b ( 4-me ) , 2c ( 4-ome ) , 2d ( 4-nme2 ) , 2e ( 4-f ) , 2f ( 4-cf3 ) , and 2 g ( 4-no2 ) , and their selectively 
 monodeuterated , electron rich analogues 2a  d - d were prepared from their 
 corresponding 1,2-bis(pyridine-2-ylethynyl)benzene ligands 3a to 3 g , and 3b - d to 3d - d , via their corresponding 
 ag complexes , as shown in scheme 1 . the electron poor 
 [ n  i  n ] complexes 2e ( 4-f ) 
 and 2f ( 4-cf3 ) were observed by h nmr to be significantly less stable in cd2cl2 solution as compared to their electron rich analogues . consequently , 2e and 2f could only be detected in a mixture 
 with their decomposition product , the analogous [ n  h our attempts to generate the electron poor complex 2 g ( 4-no2 ) yielded the corresponding [ n  h n ] complex only , due to the rapid decomposition of the targeted 
 [ n  i the 4-substituted 
 1,2-bis(pyridine-2-ylethynyl)benzene ligands 3a  c , e , f were 
 synthesized using microwave - assisted sonogashira coupling ( scheme 1 ) , following previously optimized conditions . compounds 3a ( 4-h),3b ( 4-me ) , and 3c ( 4-ome ) were prepared from 1,2-diiodobenzene and two equivalents 
 of terminal alkyne 4a  c . ligands 3e ( 4-f ) and 3f ( 4-cf3 ) were obtained 
 from 1,2-diethynylbenzene and 2-bromo-4-fluoropyridine ( 7e ) or 2-chloro-4-trifluoromethylpy - ridine ( 7f ) . the electron poor ligand 3 g ( 4-no2 ) was prepared from 1,2-diiodobenzene and 2 equiv of 4 g using sonogashira coupling with et3n as base , 
 instead of et2nh , and without microwave heating to avoid 
 side reactions . the most electron rich ligand 3d ( 4-nme2 ) was prepared from 3 g ( scheme 2 ) via bchamp reduction , followed by reductive amination of paraformaldehyde with sodium 
 cyanoborohydride . reagents 
 and conditions : ( a ) 4 g ( 2.2 equiv ) , pd(pph3)2cl2 , cui , et3n , 75 c , 5 
 h , then rt , 18 h ; ( b ) fe , acoh , 
 55 c , 1.5 h ; ( c ) ch2o , nabh3cn , acoh , 
 rt , 24 h ; ( d ) agbf4 , ch2cl2 , rt , 
 20 min ; ( e ) i2 , ch2cl2 , rt , 30 min ; 
 ( f ) 4 g ( 0.8 equiv ) , pd(pph3)2cl2 , cui , et3n , 75 c , 3 h ; ( g ) 4g - d ( 2.1 equiv ) , pd(pph3)2cl2 , cui , et3n , 75 c , 20 h. the monodeuterated ligands 3a - d to 3c - d were 
 prepared in accordance with our reported procedure , including two consecutive microwave - assisted sonogashira 
 couplings ; coupling of 1,2-diiodobenzene with one equivalent of 4a  c , generating 5a  c , was followed by coupling of the corresponding deuterated 
 terminal alkyne 4a - d to 4c - d ( scheme 1 ) . the 4-no2-substituted analogue 3g - d was prepared similarly 
 from 5 g and 4g - d , and was then converted to the 4-nme2-subsituted 3d - d via bchamp reduction 
 and subsequent reductive amination , as described above ( scheme 2 ) for the conversion of 3 g to 3d . the terminal alkynes 4a - d and 4b - d were synthesized following our published procedure via regioselective deuteration at c6 of either 
 2-chloropyridine ( 7a ) or 2-chloro-4-methylpyridine ( 7b ) using buli - lidmae , subsequent microwave mediated sonogashira 
 coupling of tms - acetylene , and tms - deprotection with kf in meoh ( scheme 1 ) . the synthetic 
 routes to the 4-meo- and 4-no2-substituted 
 terminal alkynes 4c and 4 g ( scheme 3 ) both started from the commercially 
 available 2-bromo-4-nitropyridine ( 7 g ) , whereas those 
 of their selectively monodeuterated analogues 4c - d and 4g - d started from 2-bromo-4-nitropyridine-6-d ( 7g - d , scheme 3 ) . for selective monolithiation 
 of 2,6-dibromopyridine at c-6 with n - buli , a method 
 developed by cai and co - workers was followed . successive electrophilic trapping with meod furnished 2-bromo-6-deuteropyridine 
 ( 8-d ) in nearly quantitative 
 yield . for introducing the 4-no2-group , 8-d was first converted by mcpba oxidation into its n - oxide 9-d , which was 
 then nitrated with h2so4/hno3 to 
 provide 10-d . subsequent 
 reduction of 10-d with 
 pbr3 generated the desired starting material 7g - d in high yield . sonogashira coupling of either 7 g or 7g - d with tms - acetylene at room 
 temperature yielded the tms - protected alkyne 6 g or 6g - d , following the procedure 
 described by sagitullina et al . in subsequent 
 tms - deprotection , alkynes 4c/4c - d and 4g/4g - d were selectively generated by the choice of reaction conditions . deprotection with kf in meoh at ambient temperature furnished 4-no2-substituted 4g/4g - d , whereas basic conditions using k2co3 in thf / meoh ( 1:1 ) at ambient temperature provided 4-meo - substituted 4c/4c - d as a result 
 of simultaneous tms - removal and nucleophilic replacement of the 4-no2-substituent . meod 
 ( 5 equiv ) , 78 c , 1 h , then rt , 24 h ; ( b ) mcpba , chcl3 , rt , 24 h ; ( c ) hno3/h2so4 2:1 , 110 c , 3 h ; ( d ) pbr3 , ch2cl2 , 60 c 3 h ; ( e ) tms - acetylene , pd(pph3)2cl2 , cui , et3n , 5 c , 
 1 h , then rt , 2 h ; ( f ) kf , meoh , rt , 2 h ; ( g ) k2co3 , thf / meoh 1:1 , rt , 1 h. a common approach to 
 increase xb strength is to enhance the electrophilicity of the halogen 
 bond donor using strongly electron withdrawing substituents . accordingly , perfluoroaryl and -alkyl halides 
 are frequently applied halogen bond donors in model studies . the alternative 
 approach is to increase the electron density of the halogen bond acceptor 
 by the introduction of electron donating substituents . a stronger halogen bond is often presumed to 
 be reflected by a shorter distance between the halogen bond donor 
 and the acceptor . computational studies revealed that the hammett substituent constants 
 of pyridine - based halogen bond acceptors correlate to the strength 
 of their halogen bond . strategic tuning of halogen bond 
 strength is expected to facilitate the development of halogen transfer 
 reagents and of supramolecular systems , for example . the hammett substituent constants , and the corresponding induction 
 and resonance constants f and r , 
 are reported for benzene derivatives and are not calibrated for pyridine 
 rings . to assess how well they describe electron donation / withdrawal 
 in pyridine rings , we calculated the natural atomic population ( nap ) n(n ) as well as the  
 electron population n(n ) for the 
 nitrogen atoms of 1a  g and 2a  g . the calculations were performed 
 with the computational protocol described below for the investigation 
 of equilibrium geometries and bond energies . the changes of these 
 populations , n(n ) and n(n ) , relative to 1a and 2a , respectively , are listed in table 1 , together with the corresponding hammett and resonance 
 constants . regression coefficients of 0.969 ( 1a  g ) and 0.973 ( 2a  g ) between 
 para and n(n ) , and 0.965 
 ( 1a  g ) and 0.975 ( 2a  g ) between r and n(n ) are found . we therefore used n(n ) and n(n ) 
 directly to quantify the electron withdrawing / donating properties 
 of substituents . the n nmr chemical 
 shift , n , is 
 recognized to be a sensitive tool for the assessment of the coordinative 
 bonds of nitrogen heterocycles . it has previously been 
 used for the characterization of halogen bonded complexes . upon formation of pyridine - based [ nin ] complexes , analogous to nonsubstituted 1a and 2a , 100 ppm n chemical shift changes , 
 ncoord , this chemical shift alteration is the consequence of the 
 establishment of a strong halogen bond , in which the pyridine nitrogen 
 acts as lewis base , and the introduction of a positive charge into 
 the molecular system . the bond strength of nitrogen heterocycles is 
 commonly assessed by the n nmr coordination shift , ncoord . it is defined as the n chemical 
 shift difference of a complex and of its corresponding free nitrogen 
 base ( ligand ) , i.e. , ncoord = ncomplex  nligand . a stronger coordinative bond is commonly seen to be reflected by 
 a larger |ncoord| . to evaluate the influence of substituents on the electron density 
 of the pyridine nitrogen involved in the formation of [ nin ] complexes , we acquired the n nmr chemical shift 
 for 1a  d , f and 2a  f ( figure 1 ) , ncomplex , and for their corresponding free nitrogen bases ( 4-substituted 
 pyridines and 3a  f ) , nligand . the n values were 
 detected for cd2cl2 solutions using indirect 
 detection by h , n hmbc experiments . electron donating substituents 
 in the para - position of the pyridine nitrogen increase 
 the shielding of the nitrogen , whereas electron withdrawing substituents 
 have an opposite effect . the influence of the substituents on the 
 n is comparable for the ligands and complexes 
 applied in this study . we determined the regression coefficients r for the correlation of n with both n(n ) and n(n ) , as well as para and r , both for the series of complexes 1a  d , f and 2a  f and for the corresponding series of ligands ( see si for the complete results ) . for the correlation with n(n ) , the r values are in the interval between 0.984 ( ligands for 1a  d , f ) and 0.995 ( complexes 1a  d , f ) ( figure 2 ) , whereas for the correlation 
 with n(n ) considerably lower r values , in the interval between 0.824 ( complexes 2a  f ) and 0.920 ( ligands 3a  f ) , were calculated . likewise , the regression 
 coefficients with respect to para and r were lower than the r with respect 
 to n(n ) . this finding indicates 
 that the substituent effects on the n are governed 
 by the  population rather than the total electron population 
 at the nitrogen atoms . thus , the n is primarily 
 controlled by the paramagnetic ring currents of the pyridine rings 
 rather than by diamagnetic shielding or deshielding . consequently , 
 the n change is a specific measure for the  
 donating or withdrawing property of substituents . in particular , we 
 find that fluorine , in contrast to common beliefs , dominantly acts 
 as an electron donor , via resonance , which is reflected by the comparable 
 n of the fluorine substituted 2e and 3e to those of the methyl substituted analogues 2b and 3b ( table 2 ) . the ncoord of 
 the iodine(i ) complexes do not vary to a significant extent , which 
 is in excellent agreement with previous observations of ncoord for analogous silver(i ) complexes , when 
 detected in a noncoordinating solvent and in the absence of a strongly 
 coordinating counterion . overall , the observed 
 large ncoord of 1a  d , f and 2a  f confirms formation of [ n  i  n ] complexes ; 
 however , its magnitude does not reflect interaction strength . n nmr chemical shift changes 
 ( relative to 1a or 2a , respectively ) , n , 
 of substituted pyridines (  ) , of the corresponding 1,2-bis((pyridine-2-ylethynyl)benzene ) 
 ligands 3a  f (  ) , and of their 
 [ n  i  n ] complexes , 1a  d , f (  ) and 2a  f (  ) , respectively , strongly correlate to the corresponding 
 changes in the (n ) orbital population . this indicates that 
 the variation in n is dominatingly governed by 
 the paramagnetic ring currents in the pyridine moieties . understanding the 
 factors governing the geometry of the three - center - four - electron [ n  x  n ] halogen bond is a key for the description of its nature . the solution nmr spectroscopic technique isotopic perturbation of 
 equilibrium ( ipe ) has previously been proven to be a unique tool for 
 distinguishing a rapidly equilibrating mixture from a static , symmetric 
 structure in solution , and was successfully applied for symmetry determinations 
 of hydrogen and halogen bonds , of carbocations , and of metal chelates . ipe relies on the detection of vibrational energy changes in a molecule 
 upon selective isotope labeling , commonly a hydrogen to deuterium 
 substitution close to the interaction site of interest . when analyzing 
 the mixture of the labeled and the unlabeled isotopologs of a compound , 
 two sets of signals are detected ; one set originates from the nondeuterated 
 compound , whereas the other set stems from the deuterated analogue . the small shift difference between the signals of the isotopologs 
 is called the isotope shift , obs , where n denotes the number of bonds between 
 the observed nucleus , commonly c , and the position of 
 the isotopic substitution . the observed chemical shift difference 
 is the sum of the intrinsic isotope shift , 0 , and the equilibrium isotope shift , eq , according to eq 1:1 the intrinsic isotope 
 effect , 0 , which is 
 present in all systems , is usually small and attenuates as n increases . the 0 and 0 isotope shifts , observed for the reporter 
 atoms one and two bonds from the isotopic substitution site , are negative , 
 often in the order of 0.3 ppm and 0.1 ppm , whereas 
 the sign of 0 observed 
 for reporter atoms further away may vary . the equilibrium isotope 
 effect , eq , in contrast , 
 is present only for systems involved in a dynamic equilibrium process , 
 and is zero for static systems . its magnitude depends on the equilibrium 
 constant k of the exchange process:2where d denotes the chemical 
 shift difference between the signals of the isomeric forms , i.e. , 
 halogenated n  x and nonhalogenated n , in this particular 
 case . the equilibrium constant , k , is temperature 
 dependent according to the vant hoff equation , and so is the equilibrium isotope effect , eq . we have shown that 
 the magnitude of the observed isotope shift , obs , does not allow straightforward differentiation 
 between a static [ nxn ] geometry and a dynamic [ n  xn][nx  n ] system in rapid 
 equilibrium , but the temperature dependence of obs is a reliable measure for distinguishing 
 the two systems from each other . the 
 symmetry of the [ n  i  n ] halogen bond of 2a  d was studied in solution with the 
 ipe technique using isotopolog mixtures and c { h , h } nmr detection , as described in detail earlier . similar to previous studies of halogen bond 
 symmetry , isotopolog 
 mixtures of the free ligands 3a  d were used as references for static systems in the evaluation of 
 the temperature dependence of the isotope effects ( table 3 ) . due to their low stability , 
 in combination with their poor solubility , the symmetry of the electron 
 poor complexes 3e  g could not be 
 studied experimentally . the c{h , h } experiments were run at 201.20 
 mhz . temperature interval 
 20 
 to 25 c . temperature 
 interval 10 
 to 25 c . due to minor 
 temperature dependence 
 and to limited solubility , this coefficient could not be reliably 
 determined . the temperature 
 coefficients obs for 
 complexes 2a  d ( table 3 ) are small and comparable 
 to those of the corresponding reference molecules 3a  d , in both magnitude and sign . the sum of the absolute value 
 of the observed isotope effects , |obs| , is 
 comparable for the free ligands and their corresponding [ n  i  n ] halogen bonded complexes . the overall temperature dependence 
 of the isotope effect of systems involved in rapid equilibrium , such 
 as [ n  h n ] complexes , were previously reported 
 to be significantly higher than those of their corresponding free 
 ligands . in agreement with previous studies , the obs s of c3 were largest 
 for both the free ligands 3a  d and 
 their iodine(i ) complexes 2a d , independent of the electron density of their [ nin ] bond , was further indicated by the relative magnitude of 
 the temperature coefficients . thus , a larger temperature dependence 
 was detected for the carbons closest to the position of h - to - h substitution , obs and obs . n ] complexes , 
 the magnitude of the temperature coefficients depends not only on 
 the distance of the reporter c s to the deuterium 
 substitution site ( n ) , but also on their distance 
 to the nitrogen that is directly involved in the fast equilibrium 
 process . consequently , the temperature 
 coefficients of the isotope effects of carbons further away from the 
 point of isotope substitution , yet close to the nitrogen are large 
 for dynamic , but small for static systems . for a more detailed 
 analysis of the halogen bonds and their symmetry , 
 we calculated equilibrium geometries and energies of 1a  g and 2a  g . all calculations were performed using density functional theory ( dft ) , 
 employing the b3lyp exchange and correlation functional . the lanl08 basis set in conjunction 
 with lanl2dz effective core potential were used for i , whereas 
 pople s 6 - 311+g(d , p ) basis set was used for n , and 
 pople s 6 - 311g(d , p ) basis set for the remaining 
 atoms . solvent effects were accounted for by the polarizable continuum 
 model ( pcm ) with dichloromethane as solvent . calculations predict symmetric equilibrium geometries for compounds 1a  g and 2a  g ( table 4 ) , 
 with n i covalent bond ( 2.0772.094 
  , table s31 , supporting information ) , and considerably shorter than the sum of the van der waals radii 
 of the participating atoms ( 3.53  , rxb= 0.65 ) . the bond lengths for the geometrically 
 restrained ( 2 ) and the corresponding nonrestrained analogues 
 ( 1 ) differ by less than 0.01  , indicating that 
 the strain energy required to distort the 1,2-ethynylbenzene backbone 
 is small as compared to the energetic gain upon forming a symmetric 
 three - center [ n  i  n ] halogen bond . upon formation of the [ n  i n 
 distance decreases by 0.07 to 0.2  , whereas for 2 g , it slightly increases by 0.007  . n 
 angle is linear ( 180 ) for the [ bis(pyridine)iodine ] complexes 1a  g , and is approximately 
 175.5 for the [ 1,2-bis((pyridine-2-ylethynyl)benzene)iodine ] complexes 2a  g , in excellent 
 agreement with previous reports on the geometry of halogen bonds . i bond length shows only minor dependence on the electronic 
 properties of the substituent , with a less than 0.02  difference 
 observed between the shortest and longest bonds . i bond 
 length correlates with the  electron population , n(n ) , with r of 0.953 ( 1a  g ) and 0.935 ( 2a  g ) , ( figure 3 ) . i ) and the total electron population 
 n(n ) , as reflected by the r 0.800 for 1a  g , and 
 0.700 for 2a  g . i bond length of the studied 
 complexes is governed by the  population at the nitrogen atoms . 
 to assess the stability of complexes 1a  g and 2a  g , we calculated 
 their stabilization energies according to the formal reactions shown 
 in scheme 4 . since 
 we are interested in the strength of the electronic bond rather than 
 wish to make a comparison to experimental thermochemical data , the 
 electronic energies are considered here and not the gibbs free energies . 
 whereas the geometry , i.e. , the bond lengths and bond angles , of the 
 complexes is virtually independent of electron density , their stability 
 varies by nearly 100 kj / mol , depending on the electronic nature of 
 the substituents ( table 4 , figure 4 ) . an increased 
 electron density stabilizes the [ nin ] bond ( 1b  d and 2b  d ) , whereas electron deficiency reduces the 
 stability of the complexes ( 1e  g and 2e  g ) . the correlation coefficients between 
 the stabilization energy , estab , and the natural atomic population , n(n ) , 
 are 0.991 for 1a  g and 0.989 for 2a  g , whereas the corresponding r values for the  electron population , 
 n(n ) , are significantly 
 lower , 0.851 for 1a  g , and 0.828 
 for 2a  g . thus , whereas the n  i 
 bond length proved to correlate strongly with n(n ) , the stabilization energy correlates nearly 
 perfectly with the total natural atomic population ( nap ) at the nitrogen 
 atoms . this can be rationalized from the mechanism of the three - center - four - electron 
 [ nin ] bond : the larger 
 the natural atomic population , n(n ) , the higher 
 the energies of the occupied orbitals at the nitrogen , which facilitates 
 the charge transfer to iodine(i ) . this is in line with the findings 
 of ebrahimi et al . , who investigated the nature of the [ nxn ] bond with a variety of theoretical methods . the computationally predicted variation of the [ nin ] bond strength agrees excellently with the experimentally 
 observed higher stability of electron rich complexes 2b  d as compared to the unsubstituted 2a , and the instability of 2e in solution that prevented 
 their ipe study . it should be noted that the rapid decomposition of 2 g prevented its experimental investigation completely , in 
 line with its computationally predicted instability . [ n  i  n ] complexes 1a  g and 2a  g . i bond distance with the change in 
 the (n ) population of iodine(i ) complexes of substituted pyridines 
 ( 1a  g ) (  ) and of the corresponding 
 1,2-bis((pyridine-2-ylethynyl)benzene ) ligands ( 2a  g ) (  ) . correlation of the stabilization energy ( estab ) and the change of the natural atom population at 
 the n atoms of the iodine(i ) complexes of substituted pyridines ( 1a  g ) (  ) and of the corresponding 
 1,2-bis((pyridine-2-ylethynyl)benzene ) ligands ( 2a  g ) (  ) . we emphasize that the correlations found above must not be 
 misinterpreted 
 as causal relationships . for instance , the close correlation between 
 n(n ) and estab does not indicate that the halogen bond strength is governed solely 
 by electrostatic interactions between the partial charges of the n 
 and i atoms . rather , as has been discussed , e.g. , in ref ( 10 ) , halogen bonding is caused 
 by an interplay between electrostatic , charge - transfer and not the 
 least polarization and dispersion effects . the n(n ) and n(n ) values are 
 to be considered just as indicators for the properties of the substituents , 
 in lieu of properly calibrated hammett , induction , and resonance constants . single crystals were obtained 
 via slow diffusion of hexane into dichloroethane solutions of 1c and 1f under cooling from 24 c to 20 
 c over 2 days . n 
 angle is linear ( figure 5 ) and that the iodine - centered complexes are symmetric , even in the 
 solid state ( table 5 ) , independent of their electron density . i bond lengths within a complex , lower than < 0.4% , 
 is likely due to crystal packing forces , and does not reflect a real 
 asymmetry . supporting the dft predictions above , the x - ray crystallographic 
 data corroborate that alteration of the electron density of the pyridine 
 nitrogen causes only very minor , < 2% , change in the n  i 
 bond length . solid state geometries of complexes 1c ( top , 
 ccdc-1452897 ) , 
 and 1f ( bottom , ccdc-1452897 ) , obtained by single crystal 
 x - ray crystallography . the crystal of compound 1c was obtained as a solvate , and thus each molecular unit 
 contains one molecule dichloroethane . for experimental evaluation of the electron density 
 dependence of the halogen bond strength of [ n  i  n ] complexes , we have monitored the rate of disappearance of 
 the uv absorbance of [ bis(pyridine)iodine ) ] upon iodonium 
 transfer from complexes 1a , c , d , f to 4-penten-1-ol , using a procedure described by 
 neverov and brown . the mechanistic details of halonium 
 transfer from bis(pyridine)-type complexes to alkenes are well understood . we have used pseudo - first - order conditions , with a large excess 
 of olefin ( 3.977 mm ) , and monitored the reaction proceeding 
 in dry dichloroethane solution at 25 c at the wavelength of 
 maximum change ( 1a , f : 230 nm , 1c , 257 nm , and 1d , 300 nm ) . the reactions of 1a , c , d were monitored using a cary 100 uv vis 
 spectrophotometer , whereas an applied photophysics sx-17mv stopped - flow 
 reaction analyzer was used for the fast reactions with 1f ( 4-cf3 ) . the observed rate constants ( kobs ) were obtained by nllsq fitting of the absorbance 
 versus time traces for the disappearance of the iodine(i ) complex 
 to the standard exponential model:3 the saturation profile obtained 
 when 
 plotting kobs of 1a , c , f against the alkene concentration implies 
 that the mechanism for the iodonium transfer is similar to that previously 
 proposed for bromocyclization with 4-penten-1-ol . saturation was not reached in the corresponding experiment 
 with the electron rich and slowly reacting 1d , suggesting 
 a different rate limiting step . however , in the lower alkene concentration 
 range the kobs versus [ 4-penten-1-ol ] 
 profile was linear permitting determination of the second - order rate 
 constant ( k2 ) , even for this reaction . the logarithm of the second - order rate constants ( k2 = 9.21 m s ( 1a , h ) , k2 = 1.92 m s ( 1c , och3 ) , k2 = 0.00195 m s ( 1d , n(me)2 ) , and k2 = 126.9 m s ( 1f , cf3 ) ) , normalized to 1 mm concentration of 
 added 4-substituted pyridine , as a function of the change of natural 
 atomic population , n(n ) , is shown in figure 6 . second - order rate constants 
 ( m s ) of 1a , c , d , f in iodocyclization reactions 
 with 4-penten-1-ol in the presence 
 of 4-r - pyridine ( r = h , ome , nme2 or cf3 ) , normalized 
 to 1 mm , obtained in dry dichloroethane , are shown as a function of 
 the change of natural atomic population , n(n ) . a linear correlation is seen for all but the most electron rich 
 complex 1d . the magnitude of the second - order rate constants of complexes 1a , c , d , f follows the 
 inverse order of substituent electronegativity , i.e. , k2(1f , cf3 )  k2(1a , h ) > k2(1c , och3 )  k2(1d , nme2 ) . whereas the log(k2 ) of complexes 1a , c , f correlates linearly to the change of natural atomic 
 population , n(n ) , which corresponds to the 
 hammett para , the corresponding log(k2 ) of 1d is an evident outlier ( figure 6 ) , corroborating 
 the hypothesis that the iodonium transfer mechanism for 1d is different from that of its less electron rich analogues . due to the difficulties in identifying appropriate wavelengths 
 for reaction monitoring , no kinetics experiments were undertaken for 
 the analogous 4-substituted 1,2-bis((pyridine-2-ylethynyl)benzene)iodine(i ) 
 complexes 2a  f . we studied 
 the kinetics of the dissociation of complexes 1a , c , e , f in the presence 
 of the strong xb acceptor 4-dimethylaminopyridine ( dmap ) , the free 
 base of 1d . this ligand exchange reaction is rapid due 
 to the significantly higher stability of complex 1d as 
 compared to the less electron rich complexes . the dissociation 
 rate constants ( kobs ) at 25 c ( table 6 ) were determined 
 from stopped - flow experiments by addition of dmap ( 0.15 mm ; concentration 
 at which rate of the reaction was independent of [ dmap ] ) to 1a , 1c , or 1e ( 7.68  10 m ) in dry dichloroethane at 272 nm . we measured the 
 initial rate kinetics for the formation of the dmap coordinated complex 1d . in addition , the thermodynamic activation parameters h and s , shown in table 6 , for the reactions were determined from the same experiments performed 
 at different temperatures ( table 6 ) by eyring plots of the obtained kobs rate constants . the obtained activation parameters 
 indicate that the lower the electron density of an [ n  i  n ] complex , the lower the activation barrier for iodine(i ) transfer . this observation indicates , in excellent agreement with the dft computations , 
 that a decrease in electron density of the [ n  i  n ] halogen bond decreases its strength . experiments run 
 under stopped - flow 
 with 7.68  10 m iodine(i ) complex 1a , c , f , and 0.15 mm dmap in the 
 reaction cell . observed 
 rate constants kobs determined at 298 
 k. activation parameters , 
 h and s , determined from eyring plots . electron 
 density changes do not disturb the symmetric geometry 
 of the [ nin ] halogen 
 bond of bis(pyridine)-type systems , neither in solution nor in the 
 solid state . despite having a strong influence on the strength of 
 the halogen bond , the electron density of the pyridine nitrogens the slight change 
 ( < 0.7% ) correlates only weakly to the variation in total electron 
 population , n(n ) , but much more strongly to 
 that in the  population n(n ) . this 
 observation is important to stress , as shortening of the halogen bond 
 donor  acceptor distance is one of the most commonly used characteristics 
 for categorizing halogen bond strength . the n nmr 
 chemical shift of halogen bonded complexes 
 is a good measure for the  electron population of the involved 
 nitrogen . the n nmr coordination shift of the studied 
 iodine(i ) complexes reflects the formation of the [ n  i  n ] halogen bond ; however , its magnitude does not directly reflect 
 the strength of the halogen bond . analogous lack of correlation between 
 bond energy and chemical shift was recently reported for analogous 
 tetrel bonds . the stability of 
 the [ n  i  n ] halogen 
 bond correlates to the electron density of the nitrogen halogen bond 
 acceptors . a linear correlation to the natural atomic population , 
 n(n ) of the para - substituted 
 pyridines was seen for most substituents . however , reaction kinetics 
 indicate that the iodine(i ) complex bearing the strongly resonance 
 donating n , n - dimethylamino substituent 
 has a different iodonium transfer mechanism as compared to the other 
 analogous complexes studied . alkene halogenation using the latter 
 4-nme2-substituted complex is slow . on the whole , these 
 observations may be helpful for providing a tool for thorough control 
 of electrophilic halogenation reactions . as [ bis(pyridine)iodine ] complexes are common synthetic reagents , this may be of significance 
 for the development of new , stereoselective halogenating agents in 
 the future .
we have investigated the influence 
 of electron density on the three - center 
 [ n  i 
 n]+ halogen bond . a series of [ bis(pyridine)iodine]+ and [ 1,2-bis((pyridine-2-ylethynyl)benzene)iodine]+ bf4 complexes substituted with electron 
 withdrawing and donating functionalities in the para - position of their pyridine nitrogen were synthesized and studied 
 by spectroscopic and computational methods . 
 the systematic change 
 of electron density of the pyridine nitrogens upon alteration of the para - substituent ( no2 , cf3 , h , f , 
 me , ome , nme2 ) was confirmed by 15n nmr and 
 by computation of the natural atomic population and the  electron 
 population of the nitrogen atoms . 
 formation of the [ n  i 
 n]+ halogen bond resulted in > 100 ppm 15n nmr coordination 
 shifts . 
 substituent effects on the 15n nmr chemical shift 
 are governed by the  population rather than the total electron 
 population at the nitrogens . 
 isotopic perturbation of equilibrium 
 nmr studies along with computation on the dft level indicate that 
 all studied systems possess static , symmetric [ n  i 
 n]+ halogen bonds , independent of their electron density . 
 this 
 was further confirmed by single crystal x - ray diffraction data of 
 4-substituted [ bis(pyridine)iodine]+ complexes . 
 an increased 
 electron density of the halogen bond acceptor stabilizes the [ nin]+ bond , whereas electron deficiency reduces the stability of 
 the complexes , as demonstrated by uv - kinetics and computation . in 
 contrast , the n 
 i bond length is virtually unaffected by changes 
 of the electron density . 
 the understanding of electronic effects on 
 the [ n  x  n]+ halogen bond is expected to 
 provide a useful handle for the modulation of the reactivity of [ bis(pyridine)halogen]+-type synthetic reagents .