Reaction In D2O Research Articles

Formation of H2O in the CH4-CO2 dry reforming process and its activation to this reaction over Ni-Fe/MC12A7 catalysts

Dry reforming reaction of greenhouse gas CH4 and CO2 was studied over Ni-Fe bimetallic catalyst, in which the composite support of C12A7-O2- in MCM-41 was used. The isotope 13CH4/D2O tracing experiment showed CO mainly comes from 13CHx oxidation reaction and DH comes from CHx and D2O reaction, exhibiting lattice oxygen promotes CHX oxidation and water accelerate methane conversion. XPS and TPSR-MS studies exhibited the existence of lattice oxygen in catalysts produces a little H2O to facilitate a lower starting point at the reaction temperature. On-line MS investigation found that the trace water addition in the system accelerated the adsorption of CO2 on support and promoted methane dissociation, the H2 signal appears later than CO, indicating the oxidation reaction of CHx occurs after the dissociation of CO2. Besides, TG analysis tells us the H2O may consume Cα on the catalyst in time during the reaction process to remove carbon deposition.

B2(OH)4-Mediated Reductive Transamidation of N-Acyl Benzotriazoles with Nitro Compounds En Route to Aqueous Amide Synthesis

We herein developed a reductive transamidation reaction between N-acyl benzotriazoles (AcBt) and organic nitro compounds or NaNO2 under mild conditions. This protocol employed the stable and readily available B2(OH)4 as the reducing agent and H2O as the ideal solvent. N-Deuterated amides can be synthesized when conducting the reaction in D2O. A reasonable reaction mechanism involving bond metathesis between the AcBt amide and amino boric acid intermediate was proposed to explain the unique nature of AcBt.

Preparation of Deuterium Labeled Compounds by Pd/C-Al-D2O Facilitated Selective H-D Exchange Reactions.

The chemo/regioselective H-D exchange of amino acids and synthetic building blocks by an environmentally benign Pd/C-Al-D2O catalytic system is described. Due to the importance of isotope labeled compounds in medicinal chemistry and structural biology, notably their use as improved drug candidates and biological probes, the efficient and selective deuteration methods are of great interest. The approach is based on selective H-D exchange reactions where the deuterium source is simple D2O. D2 gas is generated in situ from the reaction of aluminum and D2O, while the commercially available palladium catalyst assists the H-D exchange reaction. The high selectivity and efficiency, as well as the simplicity and safe nature of the procedure make this method an environmentally benign alternative to current alternatives.

Experimental and theoretical studies of the gas-phase reactions of O(1D) with H2O and D2O at low temperature.

Here we report the results of an experimental and theoretical study of the gas-phase reactions between O(1D) and H2O and O(1D) and D2O at room temperature and below. On the experimental side, the kinetics of these reactions have been investigated over the 50-127 K range using a continuous flow Laval nozzle apparatus, coupled with pulsed laser photolysis and pulsed laser induced fluorescence for the production and detection of O(1D) atoms respectively. Experiments were also performed at 296 K in the absence of a Laval nozzle. On the theoretical side, the existing full-dimensional ground X 1A potential energy surface for the H2O2 system involved in this process has been reinvestigated and enhanced to provide a better description of the barrierless H-atom abstraction pathway. Based on this enhanced potential energy surface, quasiclassical trajectory calculations and ring polymer molecular dynamics simulations have been performed to obtain low temperature rate constants. The measured and calculated rate constants display similar behaviour above 100 K, showing little or no variation as a function of temperature. Below 100 K, the experimental rate constants increase dramatically, in contrast to the essentially temperature independent theoretical values. The possible origins of the divergence between experiment and theory at low temperatures are discussed.

Chemical Activation of Water Molecule by Collision with Spin–Orbit-State-Selected Vanadium Cation: Quantum-Electronic-State Control of Chemical Reactivity

We have obtained absolute integral cross sections (σ's) for the reactions of spin-orbit-state-selected vanadium cations, V+[a5DJ(J = 0, 2), a5FJ(J = 1, 2), and a3FJ(J = 2, 3)], with a water molecule (H2O) in the center-of-mass collision energy range Ecm = 0.1-10.0 eV. On the basis of these state-selected σ curves (σ versus Ecm plots) observed, three reaction product channels, VO+ + H2, VH+ + OH, and VOH+ + H, from the V+ + H2O reaction are unambiguously identified. Contrary to the previous guided ion beam study of the V+(a5DJ) + D2O reaction, we have observed the formation of the VO+ + H2 channel from the V+(a5DJ) + H2O ground reactant state at low Ecm's (<3.0 eV). No spin-orbit J-state dependences for the σ curves of individual electronic states are discernible, indicating that spin-orbit interactions are weak with little effect on chemical reactivity of the titled reaction. For the three product channels identified, the triplet σ(a3FJ) values are overwhelmingly higher than the quintet σ(a5DJ) and σ(a5FJ) values, showing that the reaction is governed by a "weak quintet-triplet spin crossing" mechanism, favoring the conservation of total electron spins. The σ curves for exothermic product channels are found to exhibit a rapid decreasing profile as Ecm is increased, an observation consistent with the prediction of the charge-dipole and induced-dipole orbiting model. This experiment shows that the V+ + H2O reaction can be controlled effectively to produce predominantly the VO+ + H2 channel via the V+(a3FJ) + H2O reaction at low Ecm's (≤0.1 eV) and that the ion-molecule reaction dynamics can be altered readily by selecting the electronic state of V+ cation. On the basis of the measured Ecm thresholds for the σ(a5DJ, a5FJ, and a3FJ: VH+) and σ(a5DJ, a5FJ, and a3FJ: VOH+) curves, we have deduced upper bound values of 2.6 ± 0.2 and 4.3 ± 0.3 eV for the 0 K bond dissociation energies, D0(V+-H) and D0(V+-OH), respectively. After correcting for the kinetic energy distribution resulting from the Doppler broadening effect of the H2O molecule, we obtain D0(V+-H) = 2.2 ± 0.2 eV and D0(V+-OH) = 4.0 ± 0.3 eV, which are in agreement with D0 determinations obtained by σ curve simulations.

Decagram scale production of deuterated mineral oil and polydecene as solvents for polymer studies in neutron scattering

Decagram scale syntheses of deuterated mineral oil (d-MO) and poly(1-decene) (d-PD) were achieved by direct catalytic hydrothermal H/D exchange reaction in D2O.

Catalytic Deuterium Evolution and H/D Exchange in DNA

AbstractRecently, it has been shown that DNA catalyzes the hydrogen evolution reaction (HER) at mercury‐containing electrodes, which provide voltammetric and chronopotentiometric stripping (CPS) peaks , allowing label‐free DNA determination at very low concentrations. Here, we compared DNA catalytic HER in H2O with catalytic deuterium evolution reaction (DER) in D2O. We show that in D2O single‐stranded (ss) and double‐stranded (ds) DNAs produced CPS peaks due to DER. Compared to peaks obtained in H2O, peaks were smaller and appeared at more negative potentials. Under conditions where dsDNA did not produce any peak in D2O, this DNA produced in H2O peak . These results suggested a lack of accessible bases in the D2O surface‐attached dsDNA. This might be attributed to the greater stability of deuterated dsDNA, better resisting the electric field effects at the negatively charged interface. The process of protonation of deuterated ssDNA was very fast in contrast to that of dsDNA, which was much slower and could be followed by CPS in a time range of tens of minutes.

Communication: Proton exchange in low temperature co-mixed amorphous H2O and D2O films: The effect of the underlying Pt(111) and graphene substrates.

Isotopic exchange reactions in mixed D2O and H2O amorphous solid water (ASW) films were investigated using reflection absorption infrared spectroscopy. Nanoscale films composed of 5% D2O in H2O were deposited on Pt(111) and graphene covered Pt(111) substrates. At 130 K, we find that the reaction is strongly dependent on the substrate with the H/D exchange being significantly more rapid on the Pt(111) surface than on graphene. At 140 K, the films eventually crystallize with the final products on the two substrates being primarily HOD molecule on Pt(111) and a mixture of HOD and unreacted D2O on graphene. We demonstrate by pre-dosing H2 and O2 on Pt(111) that the observed differences in reactivity on the two substrates are likely due to the formation of hydrogen ions at the Pt(111) surface that are not formed on graphene. Once formed the mobile protons move through the ASW overlayer to initiate the H/D exchange reaction.

Mechanism and Modulation of Human Androgen Synthesis

Understanding the mechanism and regulation of androgen synthesis, catalyzed by Cytochrome P450 17A1 (CYP17), is imperative to guide drug development efforts for prostate cancer. CYP17 is a bifunctional P450 acting on multiple substrates in a spatio‐temporally regulated fashion. In the zona fasciculata of the adrenal cortex, it catalyzes the hydroxylation of progesterone and pregnenolone to produce precursors of glucocorticoids. In the adrenal zona reticularis and gonads, CYP17 also catalyzes a subsequent carbon‐carbon lyase reaction on these hydroxylated products, producing androgens. This chemically complex lyase step is not well understood, and is of key importance to help design androgen synthesis specific drugs which do not impact production of the vital corticoids.P450 mediated hydroxylation has been intensely studied and it is generally agreed that the active intermediate is the high valent oxy‐ferryl species‐Compound I (Cpd I). On the other hand, CYP17 lyase chemistry has also been hypothesized to occur through a nucleophilic attack by the peroxo anion on the carbonyl of the substrate, forming a peroxo‐hemiacetal intermediate which then decays to release product. In order to provide mechanistic insight, we made use of the proton‐dependence of the Cpd I scheme and determined the kinetic solvent isotope effects (KSIE). We observed an inverse KSIE, which is explained by the decrease in uncoupling through peroxide shunt in the D2O reactions. We cryotrapped oxy‐ferrous CYP17, employed cryoradiolysis to reduce the trapped oxy‐intermediate, followed by thermal annealing to follow the mechanism using optical spectroscopy and resonance Raman spectroscopy1. We were successful in observing a hemiacetal intermediate, which makes a strong case for peroxo anion mediated mechanism for lyase reaction.Cytochrome b5 (b5) is a small heme protein, which has been shown to enhance the lyase reaction rates 5–10 fold, but has no effect on hydroxylation. The mechanism of this selective modulation of lyase reaction is not clear. b5 has been shown to enhance product formation rates in some P450s by acting as an alternate redox donor, but a possible redox role in CYP17 lyase chemistry remains elusive. To this end, we prepared a redox inactive manganese substituted form of b5 (Mn b5) and compared the rate enhancement with Mn b5 vs. b52. To determine if b5 binding perturbs the CYP17 heme thereby affecting catalysis, we performed resonance Raman spectroscopy on substrate bound ferrous‐CO and oxy‐ferrous CYP17 as well as resting ferric CYP17 in the presence of Mn b5. We used the Nanodisc system in all our experiments to reconstitute these enzymes in known stoichiometries. We observed a 5 fold rate increase with b5 but no rate enhancement with Mn b5, suggesting a redox donor role for this protein. Although our results do not disprove the presence of allosteric interactions between b5 and CYP17, it can be argued that any allosteric interactions do not play a significant role in CYP17 mediated catalysis of lyase reaction.Support or Funding InformationThis work was supported by National Institutes of Health[GM110428]

Quantum Tunneling Enhancement of the C + H2O and C + D2O Reactions at Low Temperature.

Recent studies of neutral gas-phase reactions characterized by barriers show that certain complex forming processes involving light atoms are enhanced by quantum mechanical tunneling at low temperature. Here, we performed kinetic experiments on the activated C((3)P) + H2O reaction, observing a surprising reactivity increase below 100 K, an effect that is only partially reproduced when water is replaced by its deuterated analogue. Product measurements of H- and D-atom formation allowed us to quantify the contribution of complex stabilization to the total rate while confirming the lower tunneling efficiency of deuterium. This result, which is validated through statistical calculations of the intermediate complexes and transition states has important consequences for simulated interstellar water abundances and suggests that tunneling mechanisms could be ubiquitous in cold dense clouds.

Quantitative analysis of deuterium using the isotopic effect on quaternary 13C NMR chemical shifts

Quantitative analysis of specifically deuterated compounds can be achieved by a number of conventional methods, such as mass spectroscopy, or by quantifying the residual 1H NMR signals compared to signals from internal standards. However, site specific quantification using these methods becomes challenging when dealing with non-specifically or randomly deuterated compounds that are produced by metal catalyzed hydrothermal reactions in D2O, one of the most convenient deuteration methods. In this study, deuterium-induced NMR isotope shifts of quaternary 13C resonances neighboring deuterated sites have been utilized to quantify the degree of isotope labeling of molecular sites in non-specifically deuterated molecules. By probing 13C NMR signals while decoupling both proton and deuterium nuclei, it is possible to resolve 13C resonances of the different isotopologues based on the isotopic shifts and the degree of deuteration of the carbon atoms. We demonstrate that in different isotopologues, the same quaternary carbon, neighboring partially deuterated carbon atoms, are affected to an equal extent by relaxation. Decoupling both nuclei (1H, 2H) resolves closely separated quaternary 13C signals of the different isotopologues, and allows their accurate integration and quantification under short relaxation delays (D1 = 1 s) and hence fast accumulative spectral acquisition. We have performed a number of approaches to quantify the deuterium content at different specific sites to demonstrate a convenient and generic analysis method for use in randomly deuterated molecules, or in cases of specifically deuterated molecules where back-exchange processes may take place during work up.

A combined crossed molecular beam and quasiclassical trajectory study of the Titan-relevant N(2D) + D2O reaction

Following a recent investigation on the N(2D) + H2O reaction [Homayoon et al., J. Phys. Chem. Lett. 5, 3508 (2014)], we report on an experimental and theoretical study of the isotopologue N(2D) + D2O reaction. Crossed molecular beam (CMB) experiments were conducted at a collision energy of 10.3 kcal mol–1. Quasiclassical trajectory calculations were performed on a recent potential energy surface to derive the centre-of-mass functions necessary to simulate the CMB laboratory distributions. Excellent agreement was found. The importance of the channel leading to HON/DON was confirmed. The inclusion of this channel, in addition to that leading to the isomer HNO/DNO, can affect the models considering the coupling between nitrogen and oxygen chemistry in the upper atmosphere of Titan.

Synthesis of 2-[2H]-2-(1-methylalkyl)succinic acids

Abstract We describe a specific procedure for the synthesis of deuterium-labelled 2-(1-methylalkyl)succinate established via alkylation of diethyl malonate, Krapcho decarboxylation reaction with D2O and hydrolysis reaction. Two novel compounds, 2-[2H]-2-ethylsuccinic acid and 2-[2H]-2-(1-methylheptyl)succinic acid were prepared via this synthetic route and characterized by mass spectrometry and 1H NMR. The results showed that the 2-(1-methylalkyl)succinic acids were deuterated at the β-position, which is considered as an important reaction centre in the anaerobic degradation of n-alkanes.

Oxidative uncoupling in cysteine dioxygenase is gated by a proton-sensitive intermediate.

Cysteine dioxygenase (CDO) is a non-heme mononuclear iron enzyme that catalyzes the O2-dependent oxidation of l-cysteine (Cys) to produce cysteine sulfinic acid (CSA). This enzyme catalyzes the first committed step in Cys catabolism; thus, it is central to mammalian sulfur metabolism and redox homeostasis. Ironically, despite nearly 45 years of continued research on CDO, essentially no information has been reported with respect to its kinetic mechanism. In this work, the timing of chemical steps in the CDO kinetic mechanism is investigated by pH/pD-dependent steady-state kinetics and solvent isotope effects on kcat, kcat/KM, and (O2/CSA) coupling. Normal solvent kinetic isotope effects of 1.45 ± 0.05 and 2.0 ± 0.1 are observed in kcat-pL and kcat/KM-pL profiles, respectively. Proton inventory experiments within the pL-independent region (pL 8.5) suggest multiple solvent-exchangeable protons in flight for both kcat and kcat/KM data. The influence of solvent viscosity was also investigated to probe non-chemical steps and to verify that the apparent isotope effects were not attributable to increased solvent viscosity of D2O reactions relative to H2O. Although solvent viscosity did have a modest influence on kcat and kcat/KM, the response is not sufficient to account for the observed solvent isotope effects. This suggests that product release is only partially rate-limiting for CDO catalysis. Most crucially, proton inventory of (O2/CSA) coupling indicates that a proton-sensitive transition state directly follows O2 activation. Thus, protonation of a transient species preceding Cys oxidation is gated by protons in flight. This behavior provides valuable insight into the kinetically masked transients generated during catalysis.

Caffeic acid inhibits the formation of 7-carboxyheptyl radicals from oleic acid under flavin mononucleotide photosensitization by scavenging singlet oxygen and quenching the excited state of flavin mononucleotide.

We examined the effects of caffeic acid (CA) and related compounds on 7-carboxyheptyl radical formation. This analysis was performed using a standard D2O reaction mixture containing 4.3 mM oleic acid, 25 μM flavin mononucleotide (FMN), 160 mM phosphate buffer (pH 7.4), 10 mM cholic acid, 100 mM α-(4-pyridyl-1-oxide)-N-tert-butylnitrone, and 1 mM Fe(SO4)2(NH4)2 during irradiation with 7.8 J/cm2 at 436 nm. 7-Carboxyheptyl radical formation was inhibited by CA, catechol, gallic acid, chlorogenic acid, ferulic acid, noradrenalin, 2-hydroxybenzoic acid, 3-hydroxybenzoic acid, and 4-hydroxybenzoic acid. Quinic acid, benzoic acid, and p-anisic acid had no effect on radical formation. These results suggest that a phenol moiety is essential for these inhibitory effects. The fluorescence intensity of FMN decreased by 69% ± 2% after CA addition, suggesting that CA quenches the singlet excited state of FMN. When 1 mM CA was added to a standard reaction mixture containing 25 μM FMN, 140 mM phosphate buffer (pH 7.4), and 10 mM 4-oxo-2,2,6,6-tetramethylpiperidine, the electron spin resonance signal of 4-oxo-2,2,6,6-tetramethylpiperidinooxy disappeared. This finding suggests that singlet oxygen was scavenged completely by CA. Therefore, CA appears to inhibit 7-carboxyheptyl radical formation by scavenging singlet oxygen and quenching the excited state of FMN.

Enzyme architecture: the effect of replacement and deletion mutations of loop 6 on catalysis by triosephosphate isomerase.

Two mutations of the phosphodianion gripper loop in chicken muscle triosephosphate isomerase (cTIM) were examined: (1) the loop deletion mutant (LDM) formed by removal of residues 170–173 [Pompliano, D. L., et al. (1990) Biochemistry 29, 3186–3194] and (2) the loop 6 replacement mutant (L6RM), in which the N-terminal hinge sequence of TIM from eukaryotes, 166-PXW-168 (X = L or V), is replaced by the sequence from archaea, 166-PPE-168. The X-ray crystal structure of the L6RM shows a large displacement of the side chain of E168 from that for W168 in wild-type cTIM. Solution nuclear magnetic resonance data show that the L6RM results in significant chemical shift changes in loop 6 and surrounding regions, and that the binding of glycerol 3-phosphate (G3P) results in chemical shift changes for nuclei at the active site of the L6RM that are smaller than those of wild-type cTIM. Interactions with loop 6 of the L6RM stabilize the enediolate intermediate toward the elimination reaction catalyzed by the LDM. The LDM and L6RM result in 800000- and 23000-fold decreases, respectively, in kcat/Km for isomerization of GAP. Saturation of the LDM, but not the L6RM, by substrate and inhibitor phosphoglycolate is detected by steady-state kinetic analyses. We propose, on the basis of a comparison of X-ray crystal structures for wild-type TIM and the L6RM, that ligands bind weakly to the L6RM because a large fraction of the ligand binding energy is utilized to overcome destabilizing electrostatic interactions between the side chains of E168 and E129 that are predicted to develop in the loop-closed enzyme. Similar normalized yields of DHAP, d-DHAP, and d-GAP are formed in LDM- and L6RM-catalyzed reactions of GAP in D2O. The smaller normalized 12–13% yield of DHAP and d-DHAP observed for the mutant cTIM-catalyzed reactions compared with the 79% yield of these products for wild-type cTIM suggests that these mutations impair the transfer of a proton from O-2 to O-1 at the initial enediolate phosphate intermediate. No products are detected for the LDM-catalyzed isomerization reactions in D2O of [1-13C]GA and HPi, but the L6RM-catalyzed reaction in the presence of 0.020 M dianion gives a 2% yield of the isomerization product [2-13C,2-2H]GA.

Solvent Isotope Effect on the Dark Adaptation of Bacteriorhodopsin in Purple Membrane: Viewpoints of Kinetics and Thermodynamics

The thermal retinal isomerization from all-trans, 15-anti to 13-cis, 15-syn of bacteriorhodopsin in purple membrane in H2O and D2O during dark adaptation was investigated at 30-55 °C at neutral pH. In this temperature range, phase transition of purple membrane and destruction of the tertiary structure of bacteriorhodopsin did not take place. We found that the solvent isotope effect is inverted below about 45 °C; i.e., k(f)(D2O)/k(f)(H2O) > 1. Applying the transition state theory, the changes in enthalpy from the initial state to the transition state along the thermal trans-to-cis forward reaction coordinate, ΔH(f)*, were determined to be 24.7 ± 1.2 and 20.1 ± 0.4 kcal mol(-1) in H2O and D2O, respectively. The relative entropic change of the transition state in H2O and D2O, ΔΔS(f)* = ΔS(f)*(D2O) - ΔS(f)*(H2O), was -14.4 ± 3.9 cal mol(-1) K(-1). In addition, the Gibbs free energy of trans-to-cis thermal isomerization reaction in D2O is 0.4-0.7 kcal mol(-1) lower than that in H2O. It is the first time the entropy and enthalpy of the transition state have been quantified to elucidate the solvent isotope effect in the retinal thermal isomerization of bacteriorhodopsin during dark adaptation. The solvent isotope effect on the thermodynamics properties and kinetics implied that the hydrogen bonding in the transition state during the dark adaptation of bR is stronger than that in the initial state.

Mechanistic Insights from Reaction of α-Oxiranyl-Aldehydes with Cyanobacterial Aldehyde Deformylating Oxygenase

The biosynthesis of long-chain aliphatic hydrocarbons, which are derived from fatty acids, is widespread in Nature. The last step in this pathway involves the decarbonylation of fatty aldehydes to the corresponding alkanes or alkenes. In cyanobacteria, this is catalyzed by an aldehyde deformylating oxygenase. We have investigated the mechanism of this enzyme using substrates bearing an oxirane ring adjacent to the aldehyde carbon. The enzyme catalyzed the deformylation of these substrates to produce the corresponding oxiranes. Performing the reaction in D2O allowed the facial selectivity of proton addition to be examined by (1)H NMR spectroscopy. The proton is delivered with equal probability to either face of the oxirane ring, indicating the formation of an oxiranyl radical intermediate that is free to rotate during the reaction. Unexpectedly, the enzyme also catalyzes a side reaction in which oxiranyl-aldehydes undergo tandem deformylation to furnish alkanes two carbons shorter. We present evidence that this involves the rearrangement of the intermediate oxiranyl radical formed in the first step, resulting in aldehyde that is further deformylated in a second step. These observations provide support for a radical mechanism for deformylation and, furthermore, allow the lifetime of the radical intermediate to be estimated based on prior measurements of rate constants for the rearrangement of oxiranyl radicals.

NMR Spectroscopic Study of the Complexation Behaviors of Deuterated Cyclodextrins and [60]Fullerene

Cyclodextrins (CDxs) have been selectively deuterated using a Ru/C-catalyzed H-D exchange reaction in D2O. The structures of the deuterated CDxs barely changed and their (1)H NMR spectra became very simple, which made it possible for the deuterated CDxs to be applied to the analysis of CDx complexes. Furthermore, the deuterated CDxs allowed for the existence of the equilibrium between free and complexed CDx to be confirmed, even at rt.

A Large Solvent Isotope Effect on Protein Association Thermodynamics

Solvent reorganization can contribute significantly to the energetics of protein-protein interactions. However, our knowledge of the magnitude of the energetic contribution is limited, in part, by a dearth of quantitative experimental measurements. The biotin repressor forms a homodimer as a prerequisite to DNA binding to repress transcription initiation. At 20 °C, the dimerization reaction, which is thermodynamically coupled to binding of a small ligand, bio-5'-AMP, is characterized by a Gibbs free energy of -7 kcal/mol. This modest net dimerization free energy reflects underlying, very large opposing enthalpic and entropic driving forces of 41 ± 3 and -48 ± 3 kcal/mol, respectively. The thermodynamics have been interpreted as indicating coupling of solvent release to dimerization. In this work, this interpretation has been investigated by measuring the effect of replacing H2O with D2O on the dimerization thermodynamics. Sedimentation equilibrium measurements performed at 20 °C reveal a solvent isotope effect of -1.5 kcal/mol on the Gibbs free energy of dimerization. Analysis of the temperature dependence of the reaction in D2O indicates enthalpic and entropic contributions of 28 and -37 kcal/mol, respectively, considerably smaller than the values measured in H2O. These large solvent isotope perturbations to the thermodynamics are consistent with a significant contribution of solvent release to the dimerization reaction.