Water-assisted Mechanism Research Articles

Theoretical study on the hydrolysis mechanism of N,N‐dimethyl‐N′‐(2‐oxo‐1, 2‐dihydro‐pyrimidinyl)formamidine: Water‐assisted mechanism and cluster‐continuum model

The hydrolysis reaction of N,N-dimethyl-N'-(2-oxo-1, 2-dihydro-pyrimidinyl)formamidine (DMPFA), a model compound of the antivirus drug amidine-3TC (3TC = 2', 3'-dideoxy-3'-thiacytidine), is investigated by the hybrid density functional theory B3LYP/6-31+G (d,p) method. The hydrolysis reaction of the title compound is predicted to undergo via two pathways, each of which is a stepwise process. Path A is the addition of H2O to the C=N double bond in the amidine group to form a tetrahedral structure in its first step, and then the transfer of the H atom of hydroxyl leads to the corresponding products via four possible channels. Path B simultaneously involves the nucleophilic attack of H2O to the C atom of the C=N bond and the proton transfer to the N atom of amino group leading to the cleavage of the C-N single bond in the amidine group. The results indicate that path A is more favorable than path B in the gas phase. Moreover, to simulate the title reaction in aqueous solution, water-assisted mechanism and the cluster-continuum model, based on the SCRF/CPCM model, are taken into account in our work. The results indicate that it is rational for two water molecules served as a bridge to assist in the first step of path A and that cytosine rather than the cytosine-substituted formamide should be released from the tetrahedral intermediate via s six-membered cycle transition state (channel 2). Our calculations exhibit that the process toward the tetrahedral intermediate is the rate-determining step both in the gas phase and in aqueous solution.

Theoretical study of the hydrolysis of a model carbapenem: 1-Aza-bicyclo[3,2,1]hept-2-ent-7-one

The hydrolysis of a model carbapenem, 1-aza-bicyclo[3,2,1]hept-2-ent-7-one, has been investigated using density functional theory method at both B3LYP/6-31G(d) and B3LYP/6-311+G(d,p) level. The geometries, energies and frequencies of all the stationary points were calculated in detail. Different possible reaction mechanisms have been proposed. The outcomes show that both in the non-assisted mechanism and the water-assisted mechanism, the concerted pathway a is preferred. However, the energy barrier of water-assisted mechanism is much lower than that of non-assisted mechanism.

Reversible Gas Uptake by a Nonporous Crystalline Solid Involving Multiple Changes in Covalent Bonding

Hydrogen chloride gas (HCl) is absorbed (and reversibly released) by a nonporous crystalline solid, [CuCl2(3-Clpy)2] (3-Clpy = 3-chloropyridine), under ambient conditions leading to conversion from the blue coordination compound to the yellow salt (3-ClpyH)2[CuCl4]. These reactions require substantial motions within the crystalline solid including a change in the copper coordination environment from square planar to tetrahedral. This process also involves cleavage of the covalent bond of the gaseous molecules (H-Cl) and of coordination bonds of the molecular solid compound (Cu-N) and formation of N-H and Cu-Cl bonds. These reactions are not a single-crystal-to-single-crystal transformation; thus, the crystal structure determinations have been performed using X-ray powder diffraction. Importantly, we demonstrate that these reactions proceed in the absence of solvent or water vapor, ruling out the possibility of a water-assisted (microscopic recrystallization) mechanism, which is remarkable given all the structural changes needed for the process to take place. Gas-phase FTIR spectroscopy has permitted us to establish that this process is actually a solid-gas equilibrium, and time-resolved X-ray powder diffraction (both in situ and ex situ) has been used for the study of possible intermediates as well as the kinetics of the reaction.

Density functional theory study of water-assisted deprotonation of the C8 intermediate in the reaction of the 2-fluorenylnitrenium ion with guanosine to form a C8 adduct

A density functional theory study of the deprotonation reaction of the “ C8 intermediate (8-(2-fluorenylamino)-guanosine cation)”, which is the intermediate of reaction of 2-fluorenylnitrenium ion with guanosine, to produce the C8 adduct final product is described. The barrier to reaction is high in the gas phase and becomes substantially lower when explicit hydrogen bonding of water molecules is considered. This is consistent with the experimentally observed decay of the “ C8 intermediate” on the millisecond time scale. Bulk solvent effects caused only moderate changes in the barrier to reaction in the deprotonation reaction systems that include water molecules. Thus, the hydrogen bonding of the water molecules appears to account for most of the differences between the gas phase and aqueous solution barriers for the deprotonation reaction of the C8 intermediate to form the C8 adduct product. These results suggest that a water-assisted deprotonation mechanism transforms the “ C8 intermediate” into the C8 adduct final product in the reactions of arylnitrenium ions with guanine derivatives in aqueous environments.

The role of local structure on formic acid decomposition in supercritical water: A hybrid quantum mechanics/Monte Carlo study

We explored water-assisted decompositions of formic acid in supercritical water in terms of local structure near reactant. A hybrid quantum mechanics/molecular mechanics (QM/MM) simulation used in this paper includes QM part as first solvation shell members around the reactant. A present QM/MM approach can simulate supercritical water solution with a reasonable computational load while keeping the simulation preciseness because a density functional theory of B3LYP/6-31+G(d) level was iterated at every 1000 Monte Carlo solute moves. The formic acid converts mainly decarboxylation by water-assisted mechanism, and the coordinated water molecules play an important role for understanding supercritical water density dependence of the reaction. We analyzed a contour map based on the solute–solvent interaction energy along with the reaction pathway. Coordinated water molecule restricted the dehydration pathway by means of hydrogen bond with formic acid, however, the coordinated water promotes the decarboxylation pathway by means of stabilization of the transition state structure with one catalytic water molecule. The contour map of the pair interaction energy along the reaction path elucidates the role of local structure on reactions in supercritical water.

Ligand Topology Effects on Olefin Oxidations by Bio‐Inspired [FeII(N2Py2)] Catalysts

Linear tetradentate N2Py2 ligands can coordinate to an octahedral FeII center in three possible topologies (cis-alpha, cis-beta, and trans). While for the N,N'-bis(2-pyridylmethyl)-1,2-diaminoethane (bpmen) complex, only the cis-alpha topology has been observed, for N,N'-bis(2-pyridylmethyl)-1,2-diaminocyclohexane (bpmcn) both cis-alpha and cis-beta isomers have been reported. To date, no facile interconversion between cis-alpha and cis-beta topologies has been observed for ironII complexes even at high temperatures. However, this work provides evidence for facile interconversion in solution of cis-alpha, cis-beta, and trans topologies for [Fe(bpmpn)X2] (bpmpn=N,N'-bis(2-pyridylmethyl)-1,3-diaminopropane; X=triflate, CH3CN) complexes. As reported previously, the catalytic behavior of cis-alpha and cis-beta isomers of [Fe(bpmcn)(OTf)2] with respect to olefin oxidation depends dramatically on the geometry adopted by the iron complex. To establish a general pattern of the catalysis/topology dependence, this work presents an extended comparison of the catalytic behavior for oxidation of olefins of a family of [Fe(N2py2)] complexes that present different topologies. 18O labeling experiments provide evidence for a complex mechanistic landscape in which several pathways should be considered. Complexes with a trans topology catalyze only non-water-assisted epoxidation. In contrast, complexes with a cis-alpha topology, such as [Fe(bpmen)X2] and [Fe(alpha-bpmcn)(OTf)2], can catalyze both epoxidation and cis-dihydroxylation through a water-assisted mechanism. Surprisingly, [Fe(bpmpn)X2] and [Fe(beta-bpmcn)(OTf)2] catalyze epoxidation via a water-assisted pathway and cis-dihydroxylation via a non-water-assisted mechanism, a result that requires two independent and distinct oxidants.

Density functional study of the Hoffmann elimination of ( N-Cl), N-methylethanolamine in gas phase and in aqueous solution

The molecular mechanism of the Hoffmann elimination involving ( N-Cl), N-methylethanolamine and HO − to yield 2-methyleneamino-ethanol has been theoretically characterized by using DFT at the B3LYP/6-31++G ∗∗ computing level. The role of water as a solvent was analyzed by using both discrete and hybrid discrete-continuum models. The rearrangement proceeds along a water-assisted asynchronous concerted mechanism. The Gibbs free energy reaction barrier decreases when two water molecules are included in the reaction, one of them acting simultaneously as H + donor/acceptor to/from the nitrogen/oxygen atom of ( N-Cl), N-methylethanolamine, although not involved in a proton relay mechanism, it favours the elimination.

DFT study on the water-assisted mechanism for the reaction between VO + and NH 3 to yield VNH + and H 2O

On the basis of DFT calculations, an understanding on the catalytic effect of water in the dehydration reaction between VO + and NH 3 to yield VNH + and H 2O has been obtained. The Gibbs free energy profiles point out that the global process involves two consecutive hydrogen shifts from the nitrogen to the oxygen atom. The catalytic role is achieved by a water assisted mechanism in which water acts as proton donor and acceptor, via transition structures corresponding to a six-membered rings. The corresponding stationary points lie below both the entrance VO + + NH 3, and VNH + + H 2O, channels.

Reaction Mechanism and Tautomeric Equilibrium of 2-Mercaptopyrimidine in the Gas Phase and in Aqueous Solution: A Combined Monte Carlo and Quantum Mechanics Study

A combined Monte Carlo and quantum mechanical study was carried out to analyze the tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution. Second- and fourth-order Møller-Plesset perturbation theory calculations indicate that in the gas phase thiol (Pym-SH) is more stable than the thione (Pym-NH) by ca. 8 kcal/mol. In aqueous solution, thermodynamic perturbation theory implemented on a Monte Carlo NpT simulation indicates that both the differential enthalpy and Gibbs free energy favor the thione form. The calculated differential enthalpy is DeltaH(SH)(-->)(NH)(solv) = -1.7 kcal/mol and the differential Gibbs free energy is DeltaG(SH)(-->)(NH)(solv) = -1.9 kcal/mol. Analysis is made of the contribution of the solute-solvent hydrogen bonds and it is noted that the SH group in the thiol and NH group in the thione tautomers act exclusively as a hydrogen bond donor in aqueous solution. The proton transfer reaction between the tautomeric forms was also investigated in the gas phase and in aqueous solution. Two distinct mechanisms were considered: a direct intramolecular transfer and a water-assisted mechanism. In the gas phase, the intramolecular transfer leads to a large energy barrier of 34.4 kcal/mol, passing through a three-center transition state. The proton transfer with the assistance of one water molecule decreases the energy barrier to 17.2 kcal/mol. In solution, these calculated activation barriers are, respectively, 32.0 and 14.8 kcal/mol. The solvent effect is found to be sizable but it is considerably more important as a participant in the water-assisted mechanism than the solvent field of the solute-solvent interaction. Finally, the calculated total Gibbs free energy is used to estimate the equilibrium constant.

Understanding the Selectivity in Hydrogenation of α,β-Unsaturated Aldehydes: A Water-Assisted Mechanism

The mechanisms of the competitive CC and CO hydrogenations of the α,β-unsaturated aldehydes by [RuH2(PH3)3] are investigated by means of calculations based on density functional theory. The classical mechanism via double-bond insertion into the Ru−H bond followed by σ-bond metathesis does not explain the selectivity to the unsaturated alcohol, since the CC hydrogenation is found to be easier than the CO hydrogenation, both thermodynamically and kinetically. A new water-assisted mechanism is presented in which the CO hydrogenation is clearly favored. This allows us to explain the preferred formation of the unsaturated alcohol, particularly true in biphasic media.

Water-Assisted Oxo Mechanism for Heme Metabolism

A mechanism of heme metabolism by heme oxygenase (HO) is discussed from B3LYP density functional theory calculations. The concerted OH group attack to the alpha-carbon by the iron-hydroperoxo species is investigated using a model with full protoporphyrin IX to confirm our previous conclusion that this species does not have sufficient oxidizing power for heme oxidation (J. Am. Chem. Soc. 2004, 126, 3672). Calculated activation energies and structures of the intermediates and transition state for this process remain unchanged from those for a small model with porphine in the previous study, which shows that the inclusion of the side chain of the porphyrin ring is not essential in describing the OH group transfer. The activation barrier for a direct oxo attack to the alpha-carbon by an iron-oxo model is calculated to be 49.8 kcal/mol, the barrier height of which looks very high for the enzymatic reaction under physiological conditions. This large activation energy is due to a highly bent porphyrin structure in the transition state. However, a bridging water molecule plays an important role in reducing the porphyrin distortion in the transition state, resulting in a remarkable decrease of the activation barrier to 13.9 kcal/mol. A whole-enzyme model with about 4000 atoms is constructed to elucidate functions of the protein environment in this enzymatic reaction using QM/MM calculations. The key water molecule is fixed in the protein environment to ensure the low-barrier and regioselective heme oxidation. A water-assisted oxo mechanism of heme oxidation by heme oxygenase is proposed from these calculational results.

A quantum chemical study of the water-assisted mechanism in one-carbon unit transfer reaction catalyzed by glycinamide ribonucleotide transformylase

A theoretical study for the water-assisted mechanism in one-carbon unit transfer reaction catalyzed by glycinamide ribonucleotide transformylase (GAR Tfase) is investigated in which the proton transfers in an indirect way and the energy barrier for each transition state has been lowered about 80–100 kJ/mol when compared with the corresponding one in a no-water-involved mechanism. There are two possible pathways in each mechanism: one is concerted and the other is stepwise. Our results have verified the presumption from experiments that one water molecule can assist to achieve the whole reaction. Because the addition of this water molecule in the transition states can relax the strong strain in the unstable system and greatly lowered the energy barrier. The water-assisted paths are preferable to the no-water-involved ones and the bulk solvent effect of water is also discussed.

Solvent effects on glycine II. Water-assisted tautomerization.

The water-assisted tautomerization of glycine has been investigated at the B3LYP/6-31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine-water complex embedded in a continuum. The conformations of the tautomers in this mechanism do not display an intramolecular H bond, instead the functional groups are bridged by a water molecule. The replacement of the intramolecular H bond by the bridging water reduces the polarity of the N-H bond in the zwitterion and increases that of the O-H bond in the neutral, stabilizing the zwitterion. Both the charge transfer effects and electrostatic interactions stabilize the nonintramolecularly H-bonded zwitterion conformer over the intramolecularly hydrogen bonded one. The nonintramolecularly H-bonded neutral is favored only by charge transfer effects. Although there is no strong evidence whether the intramolecularly hydrogen bonded or non hydrogen bonded structures are favored in the bulk solution represented as a dielectric continuum, it is likely that the latter species are more stable. The free energy of activation of the water-assisted mechanism is higher than the intramolecular proton transfer channel. However, when the presumably higher conformational energy of the zwitterion reacting in the intramolecular mechanism is taken into account, both mechanisms are observed to compete. The various conformers of the neutral glycine may form via multiple proton transfer reactions through several water molecules instead of a conformational rearrangement.

Dynamic NMR properties of DOTA ligand: variable pH and temperature 1H NMR study on [K(HxDOTA)](3-x)- species.

The (1)H NMR spectra of [H(x)DOTA]((4-x)-) species are reported as a function of pH and temperature in aqueous solution. The spectra show line broadening both in ligand proton signals and also in the water proton signal by titration with KOH solution. The formation of different [K(H(x)DOTA)]((3-x)-) complexes is found to be responsible for this behaviour. At high pH the usual fluxional motions, i.e. the ring inversion and the change in the acetate arms' helicity, which are also characteristic for other but inert metal-DOTA complexes, have been detected. However, because of the kinetic lability of K(+)-O and K(+)-N coordinative bonds a new type of rearrangement appears. This new motion requires breaking of coordinative bonds in the complex and can be described as a certain type of "ring slewing" around the ring C-C bonds. At low temperature (about 270 K) the ring slewing slows down and becomes negligible compared with the ring inversion and the change in the arms' helicity. These two latter processes have the same rate. When the temperature is higher (about 320 K) the ring slewing accelerates and its rate exceeds the rate of ring inversion. At this temperature the change in the acetate arms' helicity has the same rate as the ring slewing. Additionally, in the pH range 4-5 a slow intermolecular proton exchange process has been observed between the water and the dissociable protons of [K(H(x)DOTA)]((3-x)-). A water-assisted proton exchange mechanism is proposed on the basis of the activation parameters. This finding supports the previously suggested slow proton motion hypothesis for the formation of DOTA complexes.

DFT study of the water-assisted tautomerization process between hydrated oxide, MO(H 2O) +, and dihydroxide, M(OH) 2+, cations (M=V, Nb and Ta)

Density functional theory (DFT) calculations point out that the participation of water can effectively lower the barrier height for the isomerization process between hydrated oxide cation, MO(H 2O) +, and dihydroxide cation, M(OH) 2 +, (M=V, Nb and Ta). The catalytic effect is achieved by a water-assisted mechanism in which water acts as proton donor and acceptor, via a transition structure corresponding to a six-membered ring. In the case of vanadium atom, the presence of two water molecules has been taken into account and the tautomerization becomes nearly barrierless, decreasing both the stability of the transition structures relative to intermediates and the depths of wells associated with the intermediates.

Modeling H-bonding and solvent effects in the alkylation of pyrimidine bases by a prototype quinone methide: a DFT study.

Nucleophilicity of NH(2), N3, and O(2) centers of cytosine toward a model quinone methide (o-QM) as alkylating agent has been studied using DFT computational analysis [at the B3LYP/6-311+G(d,p) level]. Specific and bulk effects of water (by C-PCM model) on the alkylation pathways have been evaluated by analyzing both unassisted and water-assisted reaction mechanisms. An ancillary water molecule, H-bonded to the alkylating agent, may interact monofunctionally with the o-QM oxygen atom (passive mechanisms) or may participate bifunctionally in cyclic hydrogen-bonded structures as a proton shuttle (active mechanisms). A comparison of the unassisted with the water-assisted reaction mechanisms has been made on the basis of activation Gibbs free energies (DeltaG(++)). The gas-phase alkylation reaction at N3 does proceed through a passive mechanism that is preferred over both the active (by -6.3 kcal mol(-1)) and the unassisted process. In contrast, in the gas phase, the active assisted processes at NH(2) and O(2) centers are both favored over their unassisted counterparts by -4.0 and -2.2 kcal mol(-1), respectively. The catalytic effect of a water molecule, in gas phase, reduces the gap between the TSs of the O(2) and NH(2) reaction pathways, but the former remains more stable. Water bulk effect significantly modifies the relative importance of the unassisted and water-assisted alkylation mechanisms, favoring the former, in comparison to the gas-phase reactions. In particular, the unassisted alkylation becomes the preferred mechanism for the reaction at both the exocyclic (NH(2)) and the heterocyclic (N3) nitrogen atoms. By contrast, alkylation at the cytosine oxygen atom is a water-catalyzed process, since in water the active water-assisted mechanism is still favored. As far as competition, among all the possible mechanisms, our calculations unambiguously suggest that the most nucleophilic site both in gas phase (naked reagents: N3 >> O(2) >or= NH(2)) and in water solution (solvated reagents: N3 >> NH(2) >> O(2)) is the heterocyclic nitrogen atom (N3) (DeltaG(++)(gas) = +7.1 kcal mol(-1), and DeltaG(++)(solv) = +13.7 kcal mol(-1)). Our investigation explains the high reactivity and selectivity of the cytosine moiety toward o-QM-like structures both in deoxymononucleoside and in a single-stranded DNA, on the basis of strong H-bonding interactions between reactants and solvent bulk effect. It also offers two general reactivity models in water, uncatalyzed and active water-catalyzed mechanisms (for nitrogen and oxygen nucleophiles, respectively), which should provide a general tool for the planning of nucleic acid modification.

O-Quinone methide as alkylating agent of nitrogen, oxygen, and sulfur nucleophiles. The role of H-bonding and solvent effects on the reactivity through a DFT computational study.

The reactivity of the alkylating agent o-quinone methide (o-QM) toward NH(3), H(2)O, and H(2)S, prototypes of nitrogen-, oxygen-, and sulfur-centered nucleophiles, has been studied by quantum chemical methods in the frame of DF theory (B3LYP) in reactions modeling its reactivity in water with biological nucleophiles. The computational analysis explores the reaction of NH(3), H(2)O, and H(2)S with o-QM, both free and H-bonded to a discrete water molecule, with the aim to rationalize the specific and general effect of the solvent on o-QM reactivity. Optimizations of stationary points were done at the B3LYP level using several basis sets [6-31G(d), 6-311+G(d,p), adding d and f functions to the S atom, 6-311+G(d,p),S(2df), and AUG-cc-pVTZ]. The activation energies calculated for the addition reactions were found to be reduced by the assistance of a water molecule, which makes easier the proton-transfer process in these alkylation reactions by at least 12.9, 10.5, and 6.0 kcal mol(-1) [at the B3LYP/AUG-cc-pVTZ//B3LYP/6-311+G(d,p) level], for ammonia, water, and hydrogen sulfide, respectively. A proper comparison of an uncatalyzed with a water-catalyzed reaction mechanism has been made on the basis of activation Gibbs free energies. In gas-phase alkylation of ammonia and water by o-QM, reactions assisted by an additional water molecule H-bonded to o-QM (water-catalyzed mechanism) are favored over their uncatalyzed counterparts by 5.6 and 4.0 kcal mol(-1) [at the B3LYP/6-311+G(d,p) level], respectively. In contrast, the hydrogen sulfide alkylation reaction in the gas phase shows a slight preference for a direct alkylation without water assistance, even though the free energy difference (DeltaDeltaG(#)) between the two reaction mechanisms is very small (by 1.0 kcal mol(-1) at the B3LYP/6-311+G(d,p),S(2df) level of theory). The bulk solvent effect, evaluated by the C-PCM model, significantly modifies the relative importance of the uncatalyzed and water-assisted alkylation mechanism by o-QM in comparison to the case in the gas phase. Unexpectedly, the uncatalyzed mechanism becomes highly favored over the catalyzed one in the alkylation reaction of ammonia (by 7.0 kcal mol(-1)) and hydrogen sulfide (by 4.0 kcal mol(-1)). In contrast, activation induced by water complexation still plays an important role in the o-QM hydration reaction in water as solvent.

A theoretical study of the aminolysis reaction of lysine 199 of human serum albumin with benzylpenicillin: consequences for immunochemistry of penicillins.

Herein, we present results of a computational study on benzylpenicillin attachment to Lys199 of human serum albumin via an aminolysis reaction. The internal geometry of the reactive part of the system was taken from previous work at the B3LYP/6-31+G* level on the water-assisted aminolysis reaction of a penicillin model compound (Díaz, N.; Suárez, D.; Sordo, T. L. J. Am. Chem. Soc. 2000, 122, 6710--6719). The protein environment around Lys199, the 6-acylamino side chain, and the 2-methyl groups of benzylpenicillin were relaxed by carrying out geometry optimizations with a hybrid QM/MM method (PM3/AMBER). Two different mechanistic routes were explored: a one-step water-assisted process and a carboxylate and water-assisted route in which the beta-lactam carboxylate and the ancillary water molecule mediate the proton transfer from the epsilon-amino group of Lys199 to the beta-lactam leaving N atom. The corresponding energy profiles in the protein combine the B3LYP/6-31+G* and PM3 energies of the reactive subsystem (benzylpenicillin + Lys199 side chain + the ancillary water molecule) and semiempirical PM3 energies of the entire system evaluated with a "divide and conquer" linear-scaling method. It is observed that penicillin haptenation to HSA can proceed through the water-assisted concerted mechanism which is calculated to have a high energy barrier of approximately 38 kcal/mol, in agreement with the experimentally observed slow reaction kinetics.

Theoretical study on oxygen exchange accompanying alkaline hydrolysis of esters and amides. The role of water for the exchange reaction

The hydrolysis of esters and amides accompanies a fast reaction, which results in exchange of carbonyl 18O to 16O coming from solvent water. The present study considered two paths as the oxygen exchange mechanism. One, Path 1 called the direct path, is the mechanism that a proton of the OH fragment directly moves from the OH to the 18O fragment in the tetrahedral intermediate. The other, Path 2 called the water-assisted mechanism, is that one water molecule assists transferring a proton to make an 18OH fragment. The MP2/6-31+G* level of theory estimated rather high Δ E gas ‡(TD) for the direct path of methylacetate and N-methylacetamide (21.8 and 19.7 kcal mol −1, respectively). The Δ E gas ‡(H 2O), the activation barrier for the water-assisted mechanism, is very low both for the ester (3.8 kcal mol −1) and for the amide (2.8 kcal mol −1). The Δ G ‡(H 2O) and Δ G ‡(OH), calculated activation free energies including solvent effect, are small in comparison with those observed for the breakdown of TD intermediates to exchange or hydrolysis products. The present MO calculation suggests that one solvent water acts as one of the reactants and facilitates both proton transfer from the OH fragment and proton acceptance from the water to form the new 18OH fragment. It is likely that the oxygen exchange reaction accompanying hydrolysis of esters and amides proceeds via the water-assisted mechanism.

Cataclastic solution creep of very soluble brittle salt as a rock analogue

Until about the late 1960s, macroscopically ductile deformation of quartz was seen as a microscopically cataclastic process by most geologists (cf. the origin of the name `mylonite'). Undulatory extinction, subgrains, recrystallised grains and even crystallographic preferred orientations were interpreted as due to water-assisted brittle deformation processes. Nowadays, by contrast, the occurrence of these optical microstructures is considered as conclusive and unequivocal evidence for dislocation creep. The abundance of these microstructures in naturally deformed rocks lead to the conclusion that dislocation creep is the most important ductile deformation mechanism within the Earth's crust. We studied whether a water-assisted brittle deformation mechanism could, in principle, be able to produce apparent `crystal plastic' microstructures, and how. To this end we performed a long-term deformation experiment using soluble brittle salt (NaClO 3) as an analogue for quartz. A single crystal of NaClO 3 was uniaxially stressed for 44 days at room temperature in the presence of a saturated NaClO 3 solution under atmospheric pressure. The crystal was microscopically studied during the experiment. It slowly deformed by cataclastic creep. First, irregular free face dissolution structures developed at highly stressed portions of the crystal. These locally developed into very fine channel-like structures, mostly oriented sub-parallel to crystallographic planes. Most of the channels developed into slits and finally into fractures. Fracture walls migrated by solution transfer leading to changes in shape of the crystal fragments. The resulting polygonal deformation microstructure could easily be mistaken for a dynamically recrystallised `crystal plastic' microstructure. Therefore, care should be taken to use such optical microstructures as conclusive evidence for dislocation creep. This is important, because the occurrence of these microstructures is the strongest argument for dislocation creep in crustal rocks.