hyperpolarization ( hp ) 
 methods are being used to improve the sensitivity of nmr and magnetic 
 resonance imaging to substrate detection . signal amplification by reversible exchange ( sabre ) corresponds 
 to one such method in which the nuclear spin order from para - hydrogen ( p - h2 ) is used to sensitize 
 a substrate . in this case , the process does not involve a change in 
 the chemical structure of the hyperpolarized substrate , as demonstrated 
 in the more traditional p - h2-induced polarization 
 ( phip ) technique pioneered by weitekamp and eisenberg . in phip , detection of a product that contains two nuclei that were 
 originally located in a single p - h2 molecule 
 is achieved and therefore a simultaneous change in the chemical identity 
 is required . nonetheless , this approach is very powerful , and detection 
 of the true reaction intermediates has been achieved , the development of nmr theoretical approaches facilitated , and the monitoring of hydrogenation products in organic transformation 
 enabled . the latter situation has led to significant 
 interest in phip as a tool for the in vivo monitoring of living systems . have 
 used the same methods to follow a number of heterogeneous reactions . in sabre , while the hp feedstock is still p - h2 , a catalyst is now used as a scaffold to temporarily 
 bind both h2 and the substrate . consequently , after ligand dissociation , there is no change in the 
 chemical identity of the hyperpolarized species . earlier studies used 
 [ ir(cod)(pcy3)(py)]bf4 , which contains the sterically 
 bulky electron - donating phosphine pcy3 as a suitable catalyst . more recently , greater hp efficiency has been 
 demonstrated for the related 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene 
 ( imes ) complex , [ ir(cod)(imes)cl ] . the iridium  phosphine system [ ir(cod)(pcy3)(py ) ] is known as crabtree s catalyst and is 
 usually associated with a role as either a hydrogenation or deuterium - transfer 
 catalyst . evidence obtained through studies 
 of the effect of the ligand electronic parameters by tolman , computation , and 
 calorimetric analysis of the bond strengths has revealed that n - heterocyclic carbenes ( nhcs ) are more electron - donating 
 than phosphines . furthermore , the work 
 of nolan and buriak has shown that the stability and activity of crabtree s 
 catalyst can be improved with such ligands . they achieve this by combining a bulky nhc , such as imes , with an 
 appreciably encumbered phosphine ( pph3 , pbn3 , pme2ph , and pnbu3 ) to deliver the most robust 
 and effective deuterium exchange catalyst . upon reaction of [ ir(cod)(pcy3)(py)]bf4 with pyridine and p - h2 , [ ir(h)2(pcy3)(py)3]bf4 formed and proved 
 to function very effectively as a sabre catalyst . indeed , measurements under sabre with its counterpart [ ir(h)2(imes)(py)3]cl yielded proton signal intensity 
 gains in free pyridine of greater than 3000-fold . these complexes completed the hp transfer step in a low 
 magnetic field in order to facilitate the interactions necessary for 
 spin - order transfer . both of these systems are examples of catalysts in which it is magnetic 
 inequivalence in the equatorial plane that provides the necessary 
 symmetry breaking that activates the two nuclei that were originally 
 located within p - h2 and now reside on 
 the metal as a pair of dihydride ligands . hence while these systems 
 contain three potential polarization acceptors in the form of pyridine , 
 only the two that are trans to hydride fulfill this role and , consequently , 
 the effective spin system involved in transfer is made up of just 
 2 hydride and 10 pyridine protons . we aim here to show that it is 
 possible to improve on the efficiency of this polarization transfer 
 catalyst by sharing the p - h2 spin order 
 with fewer protons . while this has already been demonstrated by using 
 deuterated substrates , a redesign of the catalyst to 
 include fewer exchangeable ligand sites offers another route to achieving 
 this goal . in this paper , we describe how the combination of an electron - donating 
 nhc and a phosphine produces a new set of high - activity catalysts 
 for sabre . the phosphines employed are pcy3 and pph3 , and they provide access to the well - defined complexes [ ir(h)2(imes)(mecn)2(pph3)]bf4 and 
 [ ir(h)2(imes)(mecn)2(pcy3)]bf4 . it has previously been suggested that 
 the hp efficiency of the sabre catalyst is linked to both the lifetime 
 of the metal complex and the strength of the magnetic field where 
 polarization transfer occurs . these concepts 
 are further tested here by using a flow - polarization 
 apparatus that has been previously described . in particular , we explore the ligand - exchange processes and demonstrate 
 how a number of new species are detectable , including characterization 
 of a c  h bond activation product that acts as a resting state 
 within the sabre process . in this case , it is products of the type 
 [ ir(h)2(ncme)(py)(imes)(pr3)]bf4 that 
 are dominant in the catalyst medium . the effect of the magnetic field 
 experienced by the catalyst at the point of polarization transfer 
 ( the polarization transfer field , or ptf ) is monitored experimentally 
 and shown to vary with the identity of the catalyst and detected substrate . we also demonstrate how breaking of the original p - h2 molecule symmetry through the chemical shift difference 
 in the dihydride product [ ir(h)2(ncme)(py)(imes)(pr3)]bf4 enables the wide transfer of hp within the 
 parent complex and hence their detection as examples of hyperpolarized 
 reaction intermediates . [ ir(cod){co(ch3)2}(imes)]bf4 ( 2 ) , [ ir(h)2(ncme)2(imes)(phosphine)]bf4 ( 3a and 4a ) , [ ir(h)2(py)2(imes)(pph3)]bf4 ( 3b ) , and [ ir(h)2(ncme)(py)(imes)(pph3)]bf4 ( 3c ) were prepared based on published literature 
 methods , as described in the supporting information . all nmr measurements were recorded 
 on a bruker avance iii series 400 or 500 mhz system . samples were 
 now typically dissolved in 3 ml of methanol - d4 ( 5 mm ) and contained pyridine ( 5 or 20-fold excess ) . single 
 crystals of both 3c and 5 were grown from 
 a benzene solution and analyzed on an oxford diffraction supernova 
 diffractometer . h nmr ( 400 mhz , cdcl3 , 298 k ) :  21.45 ( d , 2h , jhp = 17.27 hz ) , 1.65 ( s , 6h , ncch3 ) , 2.11 ( s , 12h , ch3 of imes ) , 
 2.38 ( s , 6h , ch3 ) , 6.957.34 ( m , 
 21h , ch , pph3 , imes ) . c{h } nmr ( 101 mhz , cdcl3 , 298 k ) :  1.0 ( ncch3 ) , 17.9 , 21.2 ( ch3 ) , 117.83 ( ncme ) , 122.2 , 122.6 ( nch ) , 127.9 , 128.9 , 129.6 ( d , ch , jcp = 11.3 hz ) , 129.8 , 132.7 , 133.1 ( ch ) , 133.9 , 134.4 6 ( d , ch , jcp = 11.0 hz ) , 135.9 , 137.6 , 138.8 ( c= ) , 164.1 ( d , ncn , jcp = 114.7 hz ) . p{h } nmr ( 162 mhz , 
 cdcl3 , 298 k ) :  18.96 . b nmr ( 160 mhz , 
 cd3cn , 298 k ) :  1.40 ( bf4 , 81% ) , 1.42 ( bf4 , 19% ) . f nmr ( 470 mhz , cd3cn , 298 k ) :  152.89 
 ( bf4 , 19% ) , 152.94 ( bf4 , 81% ) . esi ms : 802.29 [ m  ncme ] . h nmr ( 400 mhz , methanol - d4 , 296 k ) :  22.74 ( d , 2h , jhp = 18.4 hz ) , 1.97 ( s , 12h , ch3 of imes ) , 2.31 ( s , 6h , ch3 ) , 6.757.29 
 ( m , 27h , ch , pph3 , imes , py ) , 7.55 ( t , 
 2h , jhh = 7.2 hz , para h py ) , 
 7.55 ( d , 4h , jhh = 4.5 hz , ortho h py ) . c{h } nmr ( 101 mhz , methanol - d4 , 298 k ) :  17.9 , 21.2 ( ch3 ) , 122.0 , 122.3 ( nch ) , 123.6 ( ch , py ) , 127.8 , 128.7 , 129.5 ( d , ch , jcp = 11.3 hz ) , 129.7 , 132.5 , 133.1 ( ch ) , 133.9 , 134.4 , ( d , ch , jcp = 11.0 hz ) , 135.7 ( ch , py ) , 135.9 , 
 137.6 , 138.8 ( c= ) , 149.7 ( c= , py ) , 164.1 ( d , ncn , jcp = 114.7 hz ) . p{h } 
 nmr ( 162 mhz , methanol - d4 , 298 k ) :  
 22.1 . this complex was prepared in situ in an nmr tube 
 by adding 5 equiv of acetonitrile to a solution of 3b or 5 equiv of pyridine to a solution of 3a . h nmr ( 500 mhz , acetonitrile - d3 , 298 
 k ) :  22.30 ( dd , 1h , trans to pyridine , jhh = 7.21 hz , jhp = 19.44 
 hz ) , 21.10 ( dd , 1h , trans to ncch3 , jhh = 7.21 hz , jhp = 16.09 
 hz ) , 1.52 ( s , 3h , coordinated ncch3 ) , 
 1.80 ( s , 6h , ch3 ) , 2.00 ( s , free ncch3 ) , 2.15 ( s , 6h , 2  ch3 ) , 2.36 ( s , 6h , 2  ch3 ) , 
 6.81 ( d , 1h , ch= , jhh = 
 0.77 hz ) , 6.97 ( d , 1h , ch , jhh = 0.77 
 hz ) , 7.057.49 ( m , 21h , ch , pph3 , imes ) , 7.78 ( t , 1h , para h pyridine ) , 8.72 ( d , 2h , 
 ortho h pyridine . p{h } nmr ( 161 
 mhz , cd3cn , 298 k ) :  22.98 . b nmr ( 160 
 mhz , cd3cn , 298 k ) :  1.05 . f nmr ( 470 mhz , cd3cn , 298 k ) :  154.69 
 ( bf4 , 19% ) , 154.74 ( bf4 , 81% ) . n nmr ( 40.54 mhz , cdcl3 , 263 
 k ) :  177.8 ( coordinated ncch3 ) , 
 195.8 ( ncn , imes ) , 238.1 ( coordinated 
 pyridine ) . h 
 nmr ( 400 mhz , methanol - d4 , 296 k ) :  
 22.24 ( d , 2h , jhp = 18.7 hz ) , 
 1.321.96 ( m , 30h ch2 of pcy3 ) , 2.16 ( s , 6h , ch3 of acetonitrile ) , 
 2.21 ( s , 12h , ch3 of imes ) , 2.38 ( 3h , 
 m , ch of pcy3 ) , 7.08 ( m , 2h , ch , imes . c{h } nmr ( 101 mhz , cdcl3 , 298 k ) : 
  1.4 ( ncch3 ) , 16.0 , 19.8 ( ch3 ) , 25.8 , 26.2 , 27.0 , 28.4 , 30.5 , 32.8 , 33.1 
 ( ch2 ) , 118.8 ( ncme ) , 
 122.5 , 125.1 ( nch ) , 128.5 ( ch ) , 
 135.8 , 137.9 , 138.5 ( c= ) , 173.9 ( d , 
 ncn , jcp = 118.0 hz ) . p{h } nmr ( 162 mhz , methanol - d4 , 296 k ) :  18.24 . h nmr ( 400 mhz , methanol - d4 , 296 k ) :  23.83 ( d , 2h , jhp = 18.7 hz ) , 1.321.96 ( m , 30h , ch2 of pcy3 ) , 2.19 ( s , 12h , ch3 of imes ) , 2.41 ( s , 6h , ch3 of imes ) , 7.21 ( s , 4h , ch , imes ) , 7.66 ( t , 2h , 
 meta h pyridine ) , 8.01 ( s , 2h , ch , imes ) , 
 8.18 ( t , 1h , para h pyridine ) , 8.95 ( d , 2h , ortho h pyridine ) . p{h } nmr ( 162 mhz , methanol - d4 , 298 k ) :  21.9 . h nmr ( 400 mhz , methanol - d4 , 296 k ) :  23.42 ( dd , 1h , jhp = hz ) , 21.98 ( dd , 1h , jhp = hz ) , 1.131.73 ( m , 30h , ch2 of pcy3 ) , 1.83 ( s , 6h , ch3 of imes ) , 2.15 ( s , 6h , ch3 of 
 imes ) , 2.19 ( s , 3h , ch3 , acetonitrile ) , 
 2.38 ( s , 6h , ch3 of imes ) , 6.90 ( s , 2h , 
 ch= , imes ) , 7.07 ( s , 2h , ch= , imes ) , 7.16 ( t , 2h , jhh = 6.3 hz , meta h pyridine ) , 7.18 ( s , 2h , ch= , imes ) , 7.81 ( t , 1h , jhh = 8.3 hz , ortho h pyridine ) , 8.23 ( d , 2h , jhh = 4.3 hz , para h pyridine ) . p{h } nmr ( 162 mhz , methanol - d4 , 298 k ) :  22.73 . complexes 3a , 3b , and 4a were prepared and characterized by multinuclear nmr spectroscopy . the hydride ligands in these species appear as simple phosphorus - coupled 
 doublets at  21.40 , 22.70 and 22.24 , 
 in methanol - d4 at 298 k and at  
 21.45 , 22.80 , and 22.42 in cdcl3 . these resonances are used to monitor the chemical evolution of 
 these systems as they react with pyridine and acetonitrile . the first sample contained 3a in methanol - d4 and 5 equiv 
 of pyridine and 3 bar of h2 . the second contained 3b in cdcl3 and 1 equiv of ncme and 3 bar of h2 . in both cases , the hydride signals of 3a or 3b were replaced by a common species that yielded a pair of 
 coupled hydride ligand signals at  21.02 and 22.18 . this product , 3c , is the sole product in both reactions 
 and confirms that 3c is thermodynamically more stable 
 than either 3a or 3b , as illustrated by 
 scheme 1 and figure 1 . hydride region of two h nmr 
 spectra used to illustrate the conversion of 3a into 3c upon the addition of pyridine . the peak integrals for these two hydride resonances of 3c exhibit the expected 1:1 ratio , and we note that a coordinated 
 ncme signal appears at  1.48 . in 3c , the methyl 
 substituents of the imes ligand appear as three distinct sets , each 
 of six protons , in accordance with rapid rotation about the metal  carbene 
 and n  c bonds ( see the experimental section ) . the hydride ligand resonances of 3c are also well - resolved 
 and connect , according to nuclear overhauser effect methods , with 
 proton signals at  6.99 and 1.48 , which are attributed to bound 
 pyridine and ch3cn ligands , respectively . these connections 
 arise because of through - space interactions and confirm the cis - ligand 
 arrangement that is shown in figure 1 . n hmqc nmr spectrum is recorded 
 for this system ( in cdcl3 ) , where the n label 
 is present at natural abundance , as shown in figure 2 , a different set of connections become visible . now the hydride 
 signal that appears at lower field connects with a coordinated acetonitrile n signal at  177.8 through a 15.3 hz jh15n splitting ; it also connects to its ch3 partner at  1.48 . the second , higher field , hydride signal 
 at  22.18 possesses a jhn splitting of 18.5 hz and is located trans to pyridine . the n resonance of the associated coordinated pyridine ligand 
 of 3c appears at  239.1 in this nmr spectrum . in addition to these two connections , the  6.99 ( jhn = 10.6 hz ) signal of the ch = ch 
 protons in the imidazolium ring of the imes ligand shows a strong 
 correlation peak to a third n signal at  195.7 
 in this experiment . these measurements therefore locate key n ligand resonances in 3c and give a high level of confidence 
 in our product assignment ; we note that these measurements were achieved 
 in only a few hours without n labeling . the characterization 
 of 3c was further confirmed by x - ray crystallography 
 at 110 k. figure 3 shows the corresponding 
 ortep for 3c , while table 1 lists 
 key bond lengths and angles . n hmqc 
 nmr spectrum of unlabeled 3c recorded at 263 k in cdcl3 , with the resulting n data providing diagnostic 
 information on the ligand arrangement , as discussed in the text ( relative 
 expansions in the boxed areas are indicated ) . ortep diagrams of the cations 3c and 5 as 
 determined by x - ray diffraction . a series of related 
 studies were then undertaken on the pcy3 analogues of 3 . these studies revealed that , upon dissolution of 4a in methanol - d4 and the addition 
 of 5 equiv of pyridine and 3 bar of h2 , 4c was formed in a manner similar to that of 3c . it is well - known that 
 species such as 3c and 4c can undergo c h 
 activation of an o - methyl group of the mesityl ring 
 after ligand loss . aldridge and co - workers reported such an observation in the solid - state chemistry of ir(imes)(imes)(h)cl , 
 while torres et al . demonstrated that 
 [ ir(h)2(imes)(ncme)2(ppr3)]pf6 forms [ irh(imes)(ncme)2(ppr3)]pf6 upon treatment with ethylene . in this case , upon exposure of the 
 cyclometalated complex to h2 , the dihydride is re - formed . we were therefore not surprised when a sample of 4a that 
 was placed under n2 underwent h2 reductive elimination 
 to form a new product . isolation 
 of complex 5 led to the collection of x - ray - quality crystals , 
 which yielded the structure shown in figure 3 . the ir  phosphine bond lengths in 5 and the 
 related complex [ irh(imes)(ncme)2(ppr3)]pf6 are 2.3347(9 ) and 
 2.3367(17 )  and hence indistinguishable . in contrast , the corresponding 
 ir = c1 bond lengths are slightly different at 2.046(3 ) 
 vs 1.973(7 )  , in accordance with the greater electron - donating 
 power of pcy3 vs ppr3 . the corresponding 
 tolman cone angles change from 170 to 160 for these ligands . the difference in the phosphine steric bulk changes the structure 
 such that in 5 the equatorial n  ir  c and 
 n  ir  h bond angles are larger than those for [ irh(imes)(ncme)2(ppr3)]pf6 . it should be clear that the dominant species present in 
 these solutions is 3c or 4c . a series of h - selective exsy nmr experiments were therefore performed 
 in order to probe the ligand - exchange processes undergone by 3c and 4c . these data are presented in the supporting information ( section 4 ) , but our findings 
 are summarized here . in the first instance , 3c was observed 
 to undergo magnetization transfer between free and bound pyridine , 
 free and bound acetonitrile , and the two hydride sites , as illustrated 
 in scheme 2 . when the experimentally observed 
 rate of transfer of magnetization from bound pyridine into free pyridine 
 was monitored as a function of the pyridine concentration , saturation 
 behavior indicative of a dissociative process was evident at high 
 pyridine concentrations . the limiting rate constant for magnetization 
 transfer into free pyridine was determined to be 1.15  0.1 s. however , when a similar sample was examined , where 
 the initial concentrations of 3c and pyridine were 0.0152 
 and 0.0342 m , respectively , the rate of magnetization transfer into 
 free pyridine reduced to zero with increase in the acetonitrile concentration . this information suggests that it is actually acetonitrile dissociation 
 that accounts for the observed pyridine magnetization transfer . hence , 
 this process happens by secondary ligand exchange through unstable 3b as indicated in scheme 2 rather 
 than the direct dissociation of pyridine . this deduction was confirmed 
 when the effect of the acetonitrile concentration on the rate of transfer 
 of bound to free acetonitrile was explored . now exchange rate saturation 
 was again seen , but the maximum rate constant for ligand loss proved 
 to be 1.95  0.1 s. this value is twice that 
 of the limiting pyridine rate , a link that is expected if 3b were to be involved because once formed there is now an equal probability 
 of losing the magnetically labeled pyridine or the freshly bound pyridine 
 ligand . furthermore , the observed rate constant for hydride site interchange 
 is smaller than this and is affected by the ligand excess , in accordance 
 with the 16-electron reaction intermediate retaining unique hydride 
 ligand identities as expected . the color scheme shows how labeled magnetization can propagate through 
 the system , based on the indicated dissociative reactions . solvation 
 of the intermediates is to be expected , and distinct hydride ligand 
 sites are retained in these complexes . in 
 contrast , when 4c is examined , a limiting reaction rate 
 is again reached as both the pyridine and acetonitrile concentrations 
 are increased . however , now the limiting rate constant for pyridine 
 loss is 3.1  0.1 s , while that for acetonitrile 
 loss is half that , at 1.4  0.1 s. hence , 
 for 4c , the mechanism seems to be inverted , with the 
 main ligand loss process corresponding to loss of pyridine . consequently , 
 trapping with acetonitrile now leads to 4a , where two 
 identical equatorial ligands reside . the temperature dependence of 
 the observed magnetization transfer rates between the bound and free 
 ligands is detailed in the supporting information . it is interesting to note that when the hydride ligands of 3c are probed by exsy spectroscopy , no exchange into free 
 h2 is observed . this situation marks a significant difference 
 in behavior from that previously reported for 1 and 2 , where h2 loss is relatively facile . these data 
 therefore suggest that 3c and 4c are suitable 
 as sabre catalysts because they undergo ligand exchange on the nmr 
 time scale . we now describe a series of sabre - type measurements that 
 are designed to explore this hypothesis . in order to monitor these complexes 
 under sabre conditions rather than phip , a series of identical solutions were prepared , containing 
 the same amount of specified catalyst ( 1 , 2 , 3a , 3b , and 4a ) and a 20-fold 
 excess of pyridine . the total h nmr signal enhancement 
 of the three proton sites of pyridine was then plotted as a function 
 of the strength of the ptf . table 2 summarizes 
 these data , while figure 4 illustrates a typical h nmr spectrum of the organic region to demonstrate the impact 
 of sabre and figure 5 shows the corresponding 
 ptf plot for the signal amplification of the meta resonance of pyridine 
 as a function of the catalyst identity . ( a ) one - scan h nmr spectrum showing the hyperpolarized pyridine signals produced 
 under sabre with 4 . plot showing how the ptf controls both the degree of pyridine meta 
 proton signal enhancement and the phase of the signal for transfer 
 in a methanol - d4 solution using 2 ( blue ) , 1 ( red ) , 3c ( purple ) , 
 and 4c ( green ) sabre catalysts when 1 equiv of ncme and 
 20 equiv of pyridine are present in solution . surprisingly , the level of proton signal enhancement observed 
 using 4c is comparable to that found for 2 even though the ligand - exchange rates are slower . additionally , 
 the level of signal enhancement seen in the proton signals of acetonitrile , 
 phosphine , and imes ligands of 4c is substantial , albeit 
 at a lower level than that of pyridine . we further note that when 3c and 4c are employed as magnetization transfer 
 catalysts , transfer into the protons of ncme is observed . the level 
 of enhancement seen for the acetonitrile protons in these systems 
 reaches a maximum with a ptf of 20 g , as shown in figure 6 . plot showing the ptf dependence on the absolute signal 
 enhancement observed for the protons of (  ) acetonitrile ( 11-fold 
 excess ) and (  ) pyridine ( 31-fold excess ) , produced in a methanol - d4 solution using the sabre catalyst 3c at 291 k. this involved 
 taking a solution of 3a , with added pyridine , under p - h2 , and collecting a h nmr spectrum 
 at 298 k using a 45 excitation pulse . now strong phip was seen 
 for the signals that arise from the two hydride ligands of 3c , as shown in figure 7 . no signals for either 3a or 3b were visible in this nmr spectrum , and 
 these data are consistent with the previous section , which detailed 
 how 3c is the thermodynamic product of the reaction . 
 these nmr spectra , however , do reveal the presence of a further minor 
 reaction product that is not readily visible without phip . this product 
 appears as a pair of mutually coupled hydride signals at  11.89 
 ( ddd , jhh = 4.8 , jpcish = 23.6 , and jptransh = 133.8 hz ) and  20.45 ( multiplet , jhh = 4.5 , jpcish = 16.0 , and jpcish = 11.3 hz ) , which possess couplings to two inequivalent p centers . these centers were located at  2.87 ( trans to the 
 hydride resonating at  11.89 ) and 6.30 ( cis to both 
 hydrides ) in the corresponding 2d h n hmqc nmr experiment revealed that the hydride signal at  
 20.45 connected with an acetonitrile n signal 
 at  196.7 through a trans coupling . these results confirm that 
 this additional species is the ligand redistribution product [ ir(h)2(ncme)(imes)(pph3)2]bf4 ( 6 ) , with a cis h nmr spectrum of the hydride region of a methanol - d4 solution of 3c under p - h2 , revealing the pairs of hydride resonances for 3c ( major ) and 6 ( minor ) . when an analogous sample was examined using the flow 
 apparatus , after a p - h2 exposure time 
 of 30 s , the sabre effect was observed in some of the resonances of 3c and 6 . for example , the signal for the o - phenyl proton of the phosphine ligand of 3c now appears as an emission peak , a triplet at  7.05 , which 
 simplifies upon p decoupling into the expected doublet . a weaker signal at  6.99 is visible for an o - phenyl proton of the phosphine in 6 . the signal intensities 
 seen for these hyperpolarized ligand resonances proved to vary with 
 the ptf used for sabre and , in this case , were maximized when set 
 to 50 and 90 g , respectively . the o - pyridine proton 
 signal for 3c can also be seen as a sabre - enhanced signal 
 at  7.78 in these measurements . upon examination of the region 
 around  2.0 , hyperpolarized signals are also detected at  
 2.05 , 1.54 , and 1.32 for free ch3cn and bound ch3cn in 3c and 6 , respectively . these resonances 
 proved to have maximum intensity when the ptf was 20 g. additionally , 
 when the ptf field was increased to 140 g , signals for the corresponding 
 methyl protons of the imes ligands in 3c and 6 were enhanced ; they appear at  1.88 , 2.13 , and 2.39 for 3c and at  2.36 and 3.05 for 6 . these 
 observations have therefore demonstrated that the sabre effect can 
 be used to observe key resonances in these complexes at high sensitivity . we have built further on these 
 sabre studies by reexamining these reactions in conjunction with deuterium 
 labeling , with the aim of making the ligand resonances even more intense . for example , when pyridine - d5 , rather 
 than pyridine - h5 , is used , the sabre - enhanced 
 signals seen for the o - phenylphosphine protons of 3c and 6 proved to be reduced in intensity by 
 around 80% . in contrast , the corresponding signals for the ch3cn ligands of 3c and 6 were , however , 
 now 20% stronger , with the methyl resonances of their imes groups 
 showing an 8 fold increase under optimum conditions rather than the 
 4-fold seen in the experiments with pyridine - h5 . the signal enhancements for the hydride ligand signals of 3c were also increased by 20% over those seen with pyridine - h5 . the effects of deuteration are therefore 
 substantial and confirm that , by a reduction in the number of protons 
 in the spin system , the signal enhancement can be focused onto the 
 remaining resonances . for the phosphine , however , the opposite is 
 true , and hence we can deduce that its signals are actually enhanced 
 via transfer from the protons of pyridine . interestingly , when 
 a mixture of pyridine - h5 and pyridine - d5 is employed , the hydride ligands of 3b now become visible as strongly phip - enhanced signals . these 
 hydride resonances are strongly amplified by virtue of the creation 
 of a small chemical shift difference between them ; the result of this 
 process is the creation of two ab - type hydride resonances . consequently , 
 when a 45 excitation pulse is employed , these signals dominate , 
 although the signals for 3c and 6 are still 
 visible . under sabre conditions , enhanced signals for 3b are also visible at  7.09 ( the o - phenyl 
 proton of the phosphine ) , at  7.98 ( the o - pyridine 
 proton ) , and at  2.16 for its imes ligand in this experiment . furthermore , when pph3-d15 is employed instead of pph3-h15 , the hydride ligand signals of 3c and 6 appear to be 27% larger and 26% smaller , respectively . one further 
 benefit of deuteration is that the h resonances of the 
 bound pyridine - h5 ligands in these species 
 can now be clearly seen because there is no longer any overlap with 
 what would be pph3-h15 resonances . we note , however , that separation of these signals 
 can also be achieved by varying the ptf and , consequently , either 
 route can be used to confirm the resonance assignment . this means 
 that even if deuteration is not chemically viable , characterization 
 is still possible . plot of variation of the ncme h signal intensity 
 versus ptf when a 3c - derived catalyst system is employed 
 in conjunction with the specified deuterium labeling . a total of 3 
 ml of a methanol - d4 solution of 3c ( 5.5 mm ) with an 11-fold excess of ncme and a 31-fold excess 
 of pyridine relative to metal was employed in these room temperature 
 measurements . we have also studied 
 the effect of deuteration on the polarization of free ncme . when pyridine - d5 was used instead of pyridine - h5 , furthermore , if a imes - d22 ligand 
 is used , this increases further to an absolute enhancement of 49-fold . when both imes - d22 and pyridine - d5 are employed , the enhancement level rises 
 yet further to 117-fold . these data are illustrated in figure 8 and therefore demonstrate that it is possible to 
 produce a viable ncme hp transfer catalyst . we note that the cyanide 
 function plays a role in many important drugs such as astrazeneca s 
 anastrozole , which is marketed as arimidex . we further note that when p - h2 is used to examine the original solution of 3a in the 
 presence of a very small amount of pyridine ( 0.1-fold based on iridium ) 
 with methanol - h4 ( 120-fold ) in methanol - d4 , while weak signals for 3a dominate , 
 phip - enhanced signals are seen for both 3c and 6 in addition to those of two further products . these additional 
 products yield pairs of hydride signals at  20.56 ( dd , jhh = 6.1 hz , jph = 12.9 hz ) and 22.54 ( dd , jhh = 5.8 , jph = 18.6 hz ) ( 3d ) and at  20.81 ( dd , jph = 18 hz ) and  21.88 ( dd , jph = 17 hz ) ( 3e ) . species 3d was assigned 
 as [ ir(h)2(meoh)(py)(imes)(pph3 ) ] on the basis of a series of multinuclear nmr observations . h cosy experiment , the hydride signal of 3d at  
 20.56 coupled with a hydride signal at  22.54 
 and a ch3 proton signal of a bound 
 methanol - h4 ligand at  2.99 . in 
 the corresponding h p hmqc nmr experiment , 
 a p signal at  6.54 was seen for 3d . in contrast , 3e is [ ir(h)2(ncme)(py)2(pph3 ) ] , and while its nmr signals 
 are too weak for full characterization , a proton signal of the axial 
 pyridine ligand was located at  9.04 . in both of the newly 
 detected complexes , 3d and 3e , it is the 
 chemical shift of the hydride ligands that secures their identity . these unusual deductions are supported by figure 9 where part a shows the one - scan h nmr spectrum 
 that was recorded after 30 s of bubbling of p - h2 through a methanol - d4 solution 
 of 3c at a ptf of 130 g. in the hydride region of this 
 spectrum , phip - enhanced signals are seen for 3a , 3d , 3e , and 6 . in contrast , the 
 organic region shows polarized and diagnostic proton signals for bound 
 pph3 , the ch3 groups of the imes ligands , 
 the pyridine ligands , and the ncme ligands in these species . when 
 the corresponding h opsy nmr spectrum ( figure 9b ) was collected , the corresponding p - h2-enhanced signals now appear very clearly , while those 
 of 3a are suppressed , as expected , because of its high 
 symmetry . figure 9c shows the corresponding 
 normal 32-scan h nmr spectrum that was recorded under 
 true boltzmann conditions for comparison . these observations are therefore 
 fully consistent with the expected redistribution of ligands in solution 
 that allow the formation of an array of low - concentration species 
 that are not readily detectable by normal nmr methods . ( a ) h nmr 
 signals from hyperpolarized pyridine , pph3 , the ch3 groups of imes ligands , and the ncme ligands that are detected 
 as a consequence of sabre . this nmr spectrum is the result of bubbling p - h2 through a methanol - d4 solution of 3c at 130 g for 30 s prior to transfer 
 into the nmr probe for observation . ( c ) corresponding 32-scan h nmr spectrum , recorded when the sample magnetization yields 
 signals of an intensity that reflects the normal boltzmann distribution 
 rather than the hp conditions . the sample consisted of 3 ml of methanol - d4 solution of 3c ( 5.5 mm ) and a 
 20-fold excess of pyridine . this study has revealed that when 3a , 3b , and 4a are exposed to a 
 solution containing h2 , pyridine , and acetonitrile , the 
 dominant products are 3c and 4c . the ligand - exchange 
 pathways of 3c and 4c were explored using 
 exsy methods . these studies revealed that 3c undergoes 
 preferential acetonitrile loss , while for 4c , pyridine 
 is lost preferentially . these processes are dissociative in nature 
 and show the expected saturation behavior at high ligand concentrations . we further note that when a solution of 4a is left under 
 n2 , the ch bond activation product 5 is obtained . utilization of 3c and 4c as sabre catalysts 
 has also revealed that substantial enhancements in both pyridine and 
 acetonitrile can be achieved . in this case , it is the chemical and 
 magnetic inequivalence of the hydride ligands that provides the route 
 to sabre activity . this is reflected in these systems by both the 
 axial and equatorial ligands seeing different hydride couplings and 
 hence receiving sabre transfer . the efficiency of the hp of free pyridine 
 by 4a is comparable with that of ir(cod){co(ch3)2}(imes)]bf4 . we note that in the case of 4a the spin polarization derived from p - h2 is now shared with just 7 in - plane protons , while in 2 , it is 12 . consequently , we confirm that one route to maximize 
 the sabre effect is to introduce fewer protons into the complex at 
 the point of magnetization sharing . we also note that 
 while 3 is better at polarizing acetonitrile , the reverse 
 is true for 4 , with pyridine being optimally polarized . this observation is consistent with the change in the ligand - exchange 
 mechanism , where 3 dissociates acetonitrile and 4 pyridine . we have also shown that it is possible to 
 detect hyperpolarized signals that are diagnostic of the ligands surrounding 
 the metal centers through sabre . in this case , [ ir(h)2(meoh)(py)(imes)(pph3)]bf4 ( 3d ) and [ ir(h)2(ncme)(py)2(pph3)]bf4 ( 3e ) were detected 
 as a direct result of this process . these observations therefore illustrate 
 a new route to using p - h2-derived magnetization 
 to characterize reaction intermediates . two concepts have been explored 
 here to aid this process . in the first , the effect of the magnetic 
 field experienced by the sample at the point of polarization transfer 
 has been examined and is related to the efficiency of ligand hp . these 
 data revealed that it is possible to differentiate signals in the 
 same nmr region by collecting a series of h nmr spectra 
 at different ptf values . we have also completed an extensive array 
 of deuterium - labeling studies . these have confirmed that it is possible 
 by reducing the extent of magnetization sharing to dramatically increase 
 the level of transfer into the remaining h sites in the 
 catalyst system . this has been used not only to increase the level 
 of pyridine and acetonitrile polarization but to aid in the characterization 
 of the reaction intermediates 3d and 3e . we further note that when 3b is formed as the isotopomer 
 [ ir(h)2(h5-pyridine)(d5-pyridine)(imes)(pph3)]bf4 , the corresponding hydride ligand signals 
 now become visible through phip rather than the sabre effect . this 
 is a direct consequence of the small chemical shift difference that 
 exists between them and further illustrates how magnetic symmetry 
 underpins both sabre and phip observations . consequently , these 
 measurements established that sabre can be used to probe the nmr signature 
 of the ligand sphere surrounding such hyperpolarized complexes . by 
 utilizing the ptf to change the intensity of nearly overlapping resonances , 
 it is possible to clearly distinguish them . the results 
 presented here also reveal how important it is to consider the role 
 of all species present in solution when quantifying and explaining 
 the appearance of sabre - derived spectra .
the 
 hyperpolarization ( hp ) method signal amplification by reversible exchange 
 ( sabre ) uses para - hydrogen to sensitize substrate 
 detection by nmr . 
 the catalyst systems [ ir(h)2(imes)(mecn)2(r)]bf4 and [ ir(h)2(imes)(py)2(r)]bf4 [ py = pyridine ; r = pcy3 or pph3 ; imes = 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene ] , 
 which contain both an electron - donating n - heterocyclic carbene and 
 a phosphine , are used here to catalyze sabre . 
 they react with acetonitrile 
 and pyridine to produce [ ir(h)2(ncme)(py)(imes)(pph3)]bf4 and [ ir(h)2(ncme)(py)(imes)(pcy3)]bf4 , complexes that undergo ligand exchange on 
 a time scale commensurate with observation of the sabre effect , which 
 is illustrated here by the observation of both pyridine and acetonitrile 
 hp . in this study , the required symmetry breaking that underpins sabre 
 is provided for by the use of chemical inequivalence rather than the 
 previously reported magnetic inequivalence . as a consequence , 
 we show 
 that the ligand sphere of the polarization transfer catalyst itself 
 becomes hyperpolarized and hence that the high - sensitivity detection 
 of a number of reaction intermediates is possible . 
 these species include 
 [ ir(h)2(ncme)(py)(imes)(pph3)]bf4 , [ ir(h)2(meoh)(py)(imes)(pph3)]bf4 , and [ ir(h)2(ncme)(py)2(pph3)]bf4 . studies are also described that employ the deuterium - labeled 
 substrates cd3cn and c5d5n , and the 
 labeled ligands p(c6d5)3 and imes - d22 , to demonstrate that dramatically improved 
 levels of hp can be achieved as a consequence of reducing proton dilution 
 and hence polarization wastage . by a combination of these studies 
 with experiments in which the magnetic field experienced by the sample 
 at the point of polarization transfer is varied , 
 confirmation of the 
 resonance assignments is achieved . 
 furthermore , when [ ir(h)2(pyridine - h5)(pyridine - d5)(imes)(pph3)]bf4 is examined , 
 its hydride ligand signals are shown to become visible through para - hydrogen - induced polarization rather than sabre .