Large Deuterium Isotope Effect Research Articles

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination.

Kinetic studies on the intramolecular hydroamination of protected variants of 2,2-diphenylpent-4-en-1-amine were carried out under a variety of conditions with cationic gold catalysts supported by phosphine ligands. The impact of ligand on gold, protecting group on nitrogen, and solvent and additive on reaction rates was determined. The most effective reactions utilized more Lewis basic ureas, and more electron-withdrawing phosphines. A DCM/alcohol cooperative effect was quantified, and a continuum of isotope effects was measured with low KIE's in the absence of deuterated alcoholic solvent, increasing to large solvent KIE's when comparing reactions in pure MeOH to those in pure MeOH-d4. The effects are interpreted both within the context of a classic gold π-activation/protodeauration mechanism and a general acid-catalyzed mechanism without intermediate gold alkyls.

Isotope and Spin Effects Induced by Compression of Paramagnetic Molecules

The zero-point energies (ZPEs) of paramagnetic molecules, free and compressed in a C59N paramagnetic cage, were computed. The excess of energy acquired by molecules under compression depended on the deuterium and tritium isotopes which ranged from 6–8 kcal/mol for H2+ to 1.0–1.5 kcal/mol for HO• and HO2. The differences in the ZPEs of compressed isotopic molecules resulted in large deuterium and tritium isotope effects which differed for singlet and triplet spin states. The hyperfine coupling (HFC) constants for protons and 17O nuclei decreased under compression, confirming the leakage of the unpaired π-electron from the central oxygen atom of guest molecules into the system of π-electrons of the cage, and its distribution over 60 atoms of the C59N. The latter seems to be the reason why the nitrogen-14 HFCs for C59N remain almost unchanged upon encapsulation of guest molecules. The singlet-triplet splitting is shown to depend on the Coulomb interaction, which controls the sign of the exchange potential. The importance of compression effects on the functioning of enzymes as molecular compressing devices is discussed.

Periodic Graphics: The science and uses of deuterium

Chemical educator and Compound Interest blogger Andy Brunning describes how deuterium and hydrogen differ and how scientists use the isotope To download a pdf of this article, visit http://cenm.ag/deuterium. References used to create this graphic: Halford, Bethany. “ Deuterium Switcheroo Breathes Life into Old Drugs .” Chemical & Engineering News, July 4, 2016. Krumbiegel, Peter. “Large Deuterium Isotope Effects and Their Use: A Historical Review.” Isot. Environ. Health Stud. 2011, DOI: 10.1080/10256016.2011.556725 . O’Leary, Dan. “The Deeds to Deuterium.” Nat. Chem. 2012, DOI: 10.1038/nchem.1273 . Wothers, Peter. “ Heavy Water ,” Dec. 13, 2011, in Chemistry World, podcast. A collaboration between C&EN and Andy Brunning, author of the popular graphics blog Compound Interest To see more of Brunning’s work, go to compoundchem.com. To see all of C&EN’s Periodic Graphics, visit http://cenm.ag/periodicgraphics .

Revisiting Alkane Hydroxylation with m-CPBA (m-Chloroperbenzoic Acid) Catalyzed by Nickel(II) Complexes.

Mechanistic studies are performed on the alkane hydroxylation with m-CPBA (m-chloroperbenzoic acid) catalyzed by nickel(II) complexes, NiII (L). In the oxidation of cycloalkanes, NiII (TPA) acts as an efficient catalyst with a high yield and a high alcohol selectivity. In the oxidation of adamantane, the tertiary carbon is predominantly oxidized. The reaction rate shows first-order dependence on [substrate] and [NiII (L)] but is independent on [m-CPBA]; vobs =k2 [substrate][NiII (L)]. The reaction exhibited a relatively large kinetic deuterium isotope effect (KIE) of 6.7, demonstrating that the hydrogen atom abstraction is involved in the rate-limiting step of the catalytic cycle. Furthermore, NiII (L) supported by related tetradentate ligands exhibit apparently different catalytic activity, suggesting contribution of the NiII (L) in the catalytic cycle. Based on the kinetic analysis and the significant effects of O2 and CCl4 on the product distribution pattern, possible contributions of (L)NiII -O. and the aroyloxyl radical as the reactive oxidants are discussed.

Isotope Effects Induced by Molecular Compression.

Zero-point energies (ZPEs) of hydroxyl ion and hydrogen and water molecules, free and compressed in C60 cages, are computed; the excess energy acquired by molecules under compression is in the range 2-3 kcal/mol and depends on the isotopes. The differences in ZPE of compressed isotopic molecules strongly exceed those of the free molecules, resulting in the large deuterium and tritium isotope effects. These effects induced by compression are suggested as a probe for testing molecular compression of enzymatic sites; they may be important for understanding enormously large isotope effects observed in some enzymatic reactions, where they are attributed to the tunneling.

Bistable State of Protons for Low-Voltage Memories.

Molecular ferroelectrics are attracting tremendous interest because of their easy and environmental-friendly processing, low acoustic impedance, and mechanical flexibility. Their ferroelectric mechanism is mainly ascribed to the order-disorder transition of molecules such as spherical 1,4-diazabicyclo[2.2.2] octane (DABCO) and quinuclidine. Here, we present two molecular ferroelectrics, [HDABCO][TFSA] and its deuterated one [DDABCO][TFSA] (TFSA = bis(trifluoromethylsulfonyl)ammonium), whose ferroelectricity is triggered by the proton ordering. This is the first time that the protons show a thermally fluctuated bistability with a double-well potential in DABCO-based ferroelectrics. A large deuterium isotope effect (ΔT = ∼53 K) not only proves that they are hydrogen-bonded ferroelectrics but also extends the ferroelectric working temperature range to room temperature. The superfast polarization switching of 100 kHz and ultralow coercive voltage of 1 V (far less than 5 V required for commercially available ferroelectric devices), benefiting from the low energy for proton transfer, allow [DDABCO][TFSA] a great potential for memory devices with low-voltage, high-speed operation. This work should inspire further exploration of hydrogen-bonded molecular ferroelectrics for flexible and wearable devices with the low-power information storage.

Structure and Reactivity of Copper Complexes Supported by a Bulky Tripodal N4 Ligand: Copper(I)/Dioxygen Reactivity and Formation of a Hydroperoxide Copper(II) Complex

A copper(I) complex, [CuI(TIPT2aped)(CH3CN)]ClO4 (1), and two copper(II) complexes, [CuII(TIPT2aped)(Cl)]PF6 (2) and [CuII(TIPT2aped)(ClO4)]ClO4 (3), were synthesized and characterized. The reaction of 1 with dioxygen in acetone at –90 °C gave an end‐on superoxide copper(II) complex 4. The superoxide copper(II) complex 4 reacted with 2,2,6,6‐tetramethylpiperidin‐1‐ol (TEMPO‐H) and 2,6‐di‐tert‐butyl‐4‐methoxyphenol (DTBMP) to generate a hydroperoxide copper(II) complex 6. These copper‐oxygen adducts were thoroughly characterized by UV/Vis, resonance Raman, EPR, and NMR spectroscopic techniques. Complex 6 was also synthesized from the copper(II) complex 3 in the presence of hydrogen peroxide and triethylamine. The reaction of 4 with TEMPO‐H showed a relatively large kinetic deuterium isotope effect (kH/kD = 5.8) and a largely negative activation enthalpy (ΔH‡). Based on the kinetic data, the reaction mechanism for the conversion of 4 to 6 is discussed.

Targeting metallo-carbapenemases via modulation of electronic properties of cephalosporins.

The global proliferation of metallo-carbapenemase-producing Enterobacteriaceae has created an unmet need for inhibitors of these enzymes. The rational design of metallo-carbapenemase inhibitors requires detailed knowledge of their catalytic mechanisms. Nine cephalosporins, structurally identical except for the systematic substitution of electron-donating and withdrawing groups in the para position of the styrylbenzene ring, were synthesized and utilized to probe the catalytic mechanism of New Delhi metallo-β-lactamase (NDM-1). Under steady-state conditions, K(m) values were all in the micromolar range (1.5-8.1 μM), whereas k(cat) values varied widely (17-220 s(-1)). There were large solvent deuterium isotope effects for all substrates under saturating conditions, suggesting a proton transfer is involved in the rate-limiting step. Pre-steady-state UV-visible scans demonstrated the formation of short-lived intermediates for all compounds. Hammett plots yielded reaction constants (ρ) of -0.34 ± 0.02 and -1.15 ± 0.08 for intermediate formation and breakdown, respectively. Temperature-dependence experiments yielded ΔG(‡) values that were consistent with the Hammett results. These results establish the commonality of the formation of an azanide intermediate in the NDM-1-catalysed hydrolysis of a range cephalosporins with differing electronic properties. This intermediate is a promising target for judiciously designed β-lactam antibiotics that are poor NDM-1 substrates and inhibitors with enhanced active-site residence times.

Large deuterium isotope effects and their use: a historical review

Isotope effects are differences in the properties of the isotopes of an element resulting in different reaction rates of a corresponding compound, in equilibrium constants and in the spectra. Shortly after the discovery of stable isotopes of hydrogen, oxygen, and carbon, Jacob Bigeleisen formulated a theory of isotope effects and calculated possible maximum values. Large isotope effects of 2H (deuterium) against 1H (protium) were seen to possibly influence interpretations of reaction mechanisms if corresponding labelling is used. Much work was invested to ensure the safety of deuterium use in men in spite of the large isotope effect. On the other hand, large deuterium isotope effects gave rise to several practical applications. Examples are the enhancement of the stability of some technical products against oxidative and against hydrolytic degradation (oils, pharmaceuticals) as well as alterations of the detoxification metabolism of pharmaceuticals in vivo.

ChemInform Abstract: Reactions of Ionized n-Propan-1-ol in the Gas Phase

The reactions of metastable ionized n-propan-1-ol have been reinvestigated by means of extensive 2 H-labeling experiments. The major fragmentation, by loss of water, proceeds by a specific and unidirectional 1,4-hydrogen migration from the methyl group to the oxygen atom. Collision-induced dissociation of the M •+ and [M-H 2 O] •+ ions is consistent with the involvement of the distonic ion . CH 2 CH 2 CH 2 OH 2 + and, probably, the ion-neutral complex CH 2 CH 2 CH 2 •+ OH 2 in water elimination. A very minor amount of hydrogen atom expulsion also occurs from metastable CH 3 CH 2 CH 2 OH •+ radical cations; this process involves only the α-hydrogen atoms. Both water and hydrogen atom losses manifest extremely large deuterium isotope effects

Reaction of a (Salen)ruthenium(VI) Nitrido Complex with Thiols. C−H Bond Activation by (Salen)ruthenium(IV) Sulfilamido Species

The reaction of [Ru(VI)(N)(L)(MeOH)](PF(6)) [1; L = N,N'-bis(salicylidene)-o-cyclohexyldiamine dianion] with a stoichiometric amount of RSH in CH(3)CN gives the corresponding (salen)ruthenium(IV) sulfilamido species [Ru(IV){N(H)SR}(L)(NCCH(3))](PF(6)) (2a, R = (t)Bu; 2b, R = Ph). Metathesis of 2a with NaN(3) in methanol affords [Ru(IV){N(H)S(t)Bu}(L)(N(3))] (2c). 2a undergoes further reaction with 1 equiv of RSH to afford a (salen)ruthenium(III) sulfilamine species, [Ru(III){N(H)(2)S(t)Bu}(L)(NCCH(3))](PF(6)) (3). On the other hand, 2b reacts with 2 equiv of PhSH to give a (salen)ruthenium(III) ammine species [Ru(III)(NH(3))(L)(NCCH(3))](PF(6)) (4); this species can also be prepared by treatment of 1 with 3 equiv of PhSH. The X-ray structures of 2c and 4 have been determined. Kinetic studies of the reaction of 1 with excess RSH indicate the following schemes: 1 --> 2a --> 3 (R = (t)Bu), 1 --> 2b --> 4 (R = Ph). The conversion of 1 to 2 probably involves nucleophilic attack of RSH at the nitrido ligand, followed by a proton shift. The conversions of 2a to 3 and 2b to 4 are proposed to involve rate-limiting H-atom abstraction from RSH by 2a or 2b. 2a and 2b are also able to abstract H atoms from hydrocarbons with weak C-H bonds. These reactions occur with large deuterium isotope effects; the kinetic isotope effect values for the oxidation of 9,10-dihydroanthracene, 1,4-cyclohexadiene, and fluorene by 2a are 51, 56, and 11, respectively.

Intrinsic Deuterium Kinetic Isotope Effects in Glutamate Mutase Measured by an Intramolecular Competition Experiment

Kinetic isotope effects (KIEs) provide a powerful tool to interrogate transition states of both enzymic and non-enzymic reactions, provided that one can measure the intrinsic KIE on the chemical step of interest, that is, the isotope effect undiminished by other isotope-insensitive steps that may contribute to the overall rate of reaction. For small molecules reacting in solution the KIE measured usually represents the intrinsic value; however, for enzymes this is seldom the case. Here we report the first measurement of the intrinsic KIE in an adenosylcobalamin enzyme (AdoCbl, coenzyme B12) for hydrogen atom transfer from substrate to coenzyme, which is a key step in the mechanism of this class of enzymes. For the B12 enzyme glutamate mutase the intrinsic deuterium KIE for hydrogen transfer from the substrate, (2S,3S)-3-methylaspartate, to 5’-deoxyadensosine is 4.1. This value is well within the semiclassical limit for a deuterium isotope effect and is much smaller than the anomalously large KIEs previously measured in other B12 enzymes and non-enzymatic model reactions, which were attributed to extensive hydrogen tunneling. Glutamate mutase one is of a group of AdoCbl-dependent enzymes that catalyze unusual isomerization reactions that formally involve a 1,2 hydrogen atom migration and proceed through a mechanism involving carbon-based free radical intermediates (Scheme 1). Radicals are generated by homolysis of the reactive cobalt–carbon bond of the coenzyme to form cob(II)alamin, a cobalt(II) intermediate, and the 5’-deoxyadenosyl radical. The adenosyl radical then abstracts the migrating hydrogen from the substrate to form 5’-deoxyadenosine and the substrate radical. The substrate radical next undergoes rearrangement to give the product radical, which is then quenched by hydrogen transfer from 5’deoxyadenosine to give the product and regenerate the 5’deoxyadenosyl radical. Finally, recombination of the adenosyl radical and cob(II)alamin to reform the coenzyme completes the catalytic cycle. Our interest in the mechanisms by which enzymes generate free radicals, as exemplified by dependent glutamate mutase, led us to undertake an extensive set of KIE measurements to examine how hydrogen abstraction from the substrate and coenzyme homolysis are coupled together. KIE measurements using deuteriumand tritium-labeled substrates and coenzyme have proved especially informative probes of the key steps of Co C bond homolysis and hydrogen atom abstraction from substrate. Pre-steady-state measurements on a number of enzymes have shown that hydrogen abstraction is kinetically coupled to Co C bond homolysis, as evidenced by the appearance of a kinetic isotope effect on cobalt–carbon bond homolysis when the enzymes are reacted with deuterated substrates. This observation implies that the 5’-dA radical is a highenergy intermediate that only has a fleeting existence. Furthermore, the KIEs reported for several AdoCbl enzymes are extremely large (ranging from 10 to 50), which has generally been attributed to hydrogen tunneling. In particular, extensive hydrogen tunneling in methylmalonyl-CoA mutase has been deduced from the temperature dependence of the deuterium isotope effect on hydrogen transfer and Co C bond homolysis. The KIEs discussed above were all measured indirectly by UV/Vis stopped-flow spectroscopy, using the spectroscopic changes associated with Co C bond homolysis as a convenient reporter of the kinetics. Although we originally reported a very large primary deuterium isotope effect, suggestive of tunneling, for the formation of cob(II)alamin and 5’-dA upon reaction of hologlutamate mutase with deuterated substrates (kH/kD= 28 with glutamate and 35 with methylaspartate), [11]

Kinetics and Mechanism of Ketone Enolization Mediated by Magnesium Bis(hexamethyldisilazide)

Magnesium bis(hexamethyldisilazide), Mg(HMDS)(2), reacts with substoichiometric amounts of propiophenone in toluene solution at ambient temperature to form a 74:26 mixture of the enolates (E)- and (Z)-[(HMDS)(2)Mg(2)(mu-HMDS){mu-OC(Ph)=CHCH(3)}], (E)-1 and (Z)-1, which contain a pair of three-coordinate metal centers bridged by an amide and an enolate group. The compositions of (E)-1 and (Z)-1 were confirmed by solution NMR studies and also by crystallographic characterization in the solid state. Rate studies using UV-vis spectroscopy reveal the rapid and complete formation of a reaction intermediate, 2, between the ketone and magnesium, which undergoes first-order decay with rate constants independent of the concentration of excess Mg(HMDS)(2) (DeltaH++ = 17.2 +/- 0.8 kcal/mol, DeltaS++ = -11 +/- 3 cal/mol.K). The intermediate 2 has been characterized by low-temperature (1)H NMR, diffusion-ordered NMR, and IR spectroscopy and investigated by computational studies, all of which are consistent with the formulation of 2 as a three-coordinate monomer, (HMDS)(2)Mg{eta(1)-O=C(Ph)CH(2)CH(3)}. Further support for this structure is provided by the synthesis and structural characterization of two model ketone complexes, (HMDS)(2)Mg(eta(1)-O=C(t)Bu(2)) (3) and (HMDS)(2)Mg{eta(1)-O=C((t)Bu)Ph} (4). A large primary deuterium isotope effect (k(H)/k(D) = 18.9 at 295 K) indicates that proton transfer is the rate-limiting step of the reaction. The isotope effect displays a strong temperature dependence, indicative of tunneling. In combination, these data support the mechanism of enolization proceeding through the single intermediate 2 via intramolecular proton transfer from the alpha carbon of the bound ketone to the nitrogen of a bound hexamethyldisilazide.

Enantioselective Addition of Secondary Phosphines to Methacrylonitrile: Catalysis and Mechanism

A highly enantioselective intermolecular hydrophosphination reaction is described. The (Pigiphos)nickel(II)-catalyzed reaction of secondary phosphines and methacrylonitrile gives chiral 2-cyanopropylphosphines in good yield and high enantiomeric excess (ee's up to 94%; (R)-(S)-Pigiphos = bis[(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl}cyclohexylphos phine). We propose a mechanism involving coordination of methacrylonitrile to the dicationic nickel catalyst followed by 1,4-addition of the phosphine, and then, rate-determining proton transfer. This mechanism is supported by (a) the experimentally determined rate law (rate = k'[Ni][methacrylonitrile][t-Bu(2)PH]), (b) a large primary deuterium isotope effect k(H)/k(D) = 4.6(1) for the addition of t-Bu(2)PH(D) at 28.3 degrees C in toluene-d(8), (c) the isolation and characterization of the species [Ni(kappa(3)-Pigiphos)(kappaN-methacrylonitrile)](2+), and (d) DFT calculations of model compounds.

Loss of water and hydrogen atom from the n-propanol molecular cation: A theoretical study

The unimolecular dissociation of n-propanol molecular cation ( 1) has been investigated theoretically. Density functional theory (DFT) molecular orbital calculations have been performed at the UB3LYP/aug-cc-pVQZ//UB3LYP/6-31 + G(d) level to obtain pathways for water and hydrogen atom loss from 1. On the basis of the DFT results, the rate-energy dependences have been calculated for water and hydrogen atom loss from various deuterated analogues of 1 by Rice–Ramsperger–Kassel–Marcus modeling. The large kinetic deuterium isotope effects on the metastable water and hydrogen atom loss reported previously are rationalized from the obtained rate-energy dependences.

Chain Amplification in Photoreactions ofN-Alkoxypyridinium Salts with Alcohols: Mechanism and Kinetics

Photosensitized electron transfer from a variety of singlet- and triplet-excited donors to N-methoxypyridinium salts leads to N-O bond cleavage. Hydrogen atom abstraction by the resulting methoxy radical from an added alcohol generates an alpha-hydroxy radical that reduces another pyridinium molecule, thus leading to chain propagation. For example, thioxanthone-sensitized reactions of 4-cyano-N-methoxypyridinium, P1, with several aliphatic and benzyl alcohols gave quantum yields for products formation (an aldehyde or a ketone and protonated 4-cyanopyridinium) of approximately 15-20, at reactant concentrations of approximately 0.02-0.04 M. The reaction can also be sensitized with triplet benzopheone, which in this case acts as an electron donor. Energetic limitations on chain propagation are imposed by the relationship between the oxidation potential of the alpha-hydroxy radical and the reduction potential of the pyridinium salt. The chain reactions proceed despite approximately 0.25 eV endothermicity for the electron-transfer step. Chain reactions with the harder-to-reduce 4-phenyl-N-methoxypyridinium, however, are limited in scope because of increased endothermicity for electron transfer. The thioxanthone-sensitized reaction of P1 with benzhydrol was studied in detail by a combination of steady state and transient kinetics. The bimolecular rate constants for the chain propagation reactions:hydrogen atom abstraction by the methoxy radical and electron transfer from the diphenylketyl radical to P1 are approximately 6 x 10(6) and 1.1 x 10(6) M(-1) s(-1), respectively. The kinetic data indicate that deuterium atom abstraction by the methoxy radical from the solvent, acetonitrile-d(3), is a dominant chain-terminating process. Because of a large deuterium isotope effect, approximately 7, the quantum amplification is strongly suppressed when the reaction is carried out in acetonitrile.

Steric compression and twist in o-hydroxy acyl aromatics with intramolecular hydrogen bonding

A series of o-hydroxy acyl aromatics of the type 1,3-diacetyl-2,4,6-trihydroxybenzene ( 1), 6-methoxy-1,3-diacetyl-2,4-dihydroxy- ( 2), 2,4,6-trihydroxy-1,3,5-triacetylbenzene ( 3) and 1-acetyl-2-naphthol ( 4) have been investigated by means of single crystal X-ray diffraction, solution and solid state NMR spectroscopy and theoretical calculations. The structures of 1 and 2 exhibit interesting hydrogen bonds, planar structures and have, as a consequence, unexpected geometrical parameters (interatomic distances, bond lengths and valence angles) and depletion of electron density of the aromatic rings. Also significant packing effects are present. For 4, a twist of the carbonyl group is observed together with an out of plane bending of the C–C O bond leading to the formation of a C O⋯H–O–C hydrogen bond which is almost coplanar with the naphthalene rings. Solid state NMR spectra show lack of C 3 symmetry for 3. Solution NMR spectra show-in the case of 1 and 2-quite different behaviour. A complex averaging-observed for 1 in solution-is unravelled at low temperature. Compounds 1– 3 show large two-bond deuterium isotope effects, 2ΔC-2(OD), on 13C chemical shifts. This indicates strong hydrogen bonds. These can be understood in terms of an electronic effect caused by bond localisation of the benzene ring and a steric effect caused by either neighbouring CH 3CO, OH or OCH 3 groups leading to shorter OH⋯O and O⋯O distances and, consequently, stronger hydrogen bonds. A general scheme for distinguishing between steric twist (as seen in 4) and steric compression as seen in 1– 3 is suggested. An experimental method based on isotope effects at the chelate proton of compounds deuteriated at the CD 3CO groups is demonstrated. A Bader atom in molecules is done to investigate hydrogen bonding.

Synthetic, Structural, and Mechanistic Aspects of an Amine Activation Process Mediated at a Zwitterionic Pd(II) Center

A zwitterionic palladium complex [[Ph(2)BP(2)]Pd(THF)(2)][OTf] (1) (where [Ph(2)BP(2)] = [Ph(2)B(CH(2)PPh(2))(2)](-)) reacts with trialkylamines to activate a C-H bond adjacent to the amine N atom, thereby producing iminium adduct complexes [Ph(2)BP(2)]Pd(N,C:eta(2)-NR(2)CHR'). In all cases examined the amine activation process is selective for the secondary C-H bond position adjacent to the N atom. These palladacycles undergo facile beta-hydride elimination/olefin reinsertion processes as evident from deuterium scrambling studies and chemical trap studies. The kinetics of the amine activation process was explored, and beta-hydride elimination appears to be the rate-limiting step. A large kinetic deuterium isotope effect for the amine activation process is evident. The reaction profile in less polar solvents such as benzene and toluene is different at room temperature and leads to dimeric [[Ph(2)BP(2)]Pd](2) (4) as the dominant palladium product. Low-temperature toluene-d(8) experiments proceed more cleanly, and intermediates assigned as [Ph(2)BP(2)]Pd(NEt(3))(OTf) and the iminium hydride species [[Ph(2)BP(2)]Pd(H)(Et(2)N=CHCH(3))][OTf] are directly observed. The complex (Ph(2)SiP(2))Pd(OTf)(2) (14) was also studied for amine activation and generates dimeric [(Ph(2)SiP(2))Pd](2)[OTf](2) (16) as the dominant palladium product. These collective data are discussed with respect to the mechanism of the amine activation and, in particular, the influence that solvent polarity and charge have on the overall reaction profile.

Hydrocarbon C—H Bond Activation by Rhodium Porphyrins

AbstractFor Abstract see ChemInform Abstract in Full Text.

Role of Arg100 in the active site of adenosylcobalamin-dependent glutamate mutase.

Arginine-100 is involved in recognizing the gamma carboxylate of the substrate in glutamate mutase. To investigate its role in substrate binding and catalysis, this residue was mutated to lysine, tyrosine, and methionine. The effect of these mutations was to reduce k(cat) by 120-320-fold and to increase K(m(apparent)) for glutamate by 13-22-fold; K(m(apparent)) for adenosylcobalamin is little changed by these mutations. Even at saturating substrate concentrations, no cob(II)alamin could be detected in the UV-visible spectra of the Arg100Tyr and Arg100Met mutants. However, in the Arg100Lys mutant cob(II)alamin accumulated to concentrations similar to wild-type enzyme, which allowed the pre-steady-state kinetics of adenosylcobalamin homolysis to be investigated by stopped-flow spectroscopy. It was found that homolysis of the coenzyme is slower by an order of magnitude, compared with wild-type enzyme. Furthermore, glutamate binding is significantly weakened, so much so that the reaction exhibits second-order kinetics over the range of substrate concentrations used. The Arg100Lys mutant does not exhibit the very large deuterium isotope effects that are observed for homolysis of the coenzyme when the wild-type enzyme is reacted with deuterated substrates; this suggests that homolysis is slowed relative to hydrogen abstraction by this mutation.