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PubMed1996

Crystal structure of a eukaryotic (pea seedling) copper-containing amine oxidase at 2.2 A resolution.

BACKGROUND: Copper-containing amine oxidases catalyze the oxidative deamination of primary amines to aldehydes, in a reaction that requires free radicals. These enzymes are important in many biological processes, including cell differentiation and growth, would healing, detoxification and signalling. The catalytic reaction requires a redox cofactor, topa quinone (TPQ), which is derived by post-translational modification of an invariant tyrosine residue. Both the biogenesis of the TPQ cofactor and the reaction catalyzed by the enzyme require the presence of a copper atom at the active site. The crystal structure of a prokaryotic copper amine oxidase from E. coli (ECAO) has recently been reported. RESULTS: The first structure of a eukaryotic (pea seedling) amine oxidase (PSAO) has been solved and refined at 2.2 A resolution. The crystallographic phases were derived from a single phosphotungstic acid derivative. The positions of the tungsten atoms in the W12 clusters were obtained by molecular replacement using E. coli amine oxidase as a search model. The methodology avoided bias from the search model, and provides an essentially independent view of a eukaryotic amine oxidase. The PSAO molecule is a homodimer; each subunit has three domains. The active site of each subunit lies near an edge of the beta-sandwich of the largest domain, but is not accessible from the solvent. The essential active-site copper atom is coordinated by three histidine side chains and two water molecules in an approximately square-pyramidal arrangement. All the atoms of the TPQ cofactor are unambiguously defined, the shortest distance to the copper atom being approximately 6 A. CONCLUSIONS: There is considerable structural homology between PSAO and ECAO. A combination of evidence from both structures indicates that the TPQ side chain is sufficiently flexible to permit the aromatic grouf to rotate about the Cbeta-Cgamma bond, and to move between bonding and non-bonding positions with respect to the Cu atom. Conformational flexibility is also required at the surface of the molecule to allow the substrates access to the active site, which is inaccessible to solvent, as expected for an enzyme that uses radical chemistry.

Amine Oxidase (Copper-Containing)↗
PubMed2003

Inhibition of six copper-containing amine oxidases by the antidepressant drug tranylcypromine.

Potential inhibitory effects of the clinically utilized monoamine oxidase inhibitor tranylcypromine (TCP) on mammalian, plant, bacterial, and fungal copper-containing amine oxidases have been examined. The following enzymes have been investigated: human kidney diamine oxidase (HKAO), bovine plasma amine oxidase (BPAO), equine plasma amine oxidase (EPAO), pea seedling amine oxidase (PSAO), Arthrobacter globiformis amine oxidase (AGAO), and Pichia pastoris lysyl oxidase (PPLO). Only BPAO, EPAO, and AGAO were found to lose significant levels of activity when incubated with varying amounts of TCP. Inhibition of BPAO was completely reversible, with dialysis restoring full activity. TCP inhibition of AGAO was also found to be ultimately reversible; however, dialysis did not remove all bound compounds. Chemical displacement with either substrate or a substrate analogue successfully removed all bound TCP, indicating that this compound has a high affinity for the active site of AGAO. The notable lack of TCP inhibition on HKAO argues against the inhibition of diamine oxidase as a potential source for some of the deleterious side effects occurring in patients treated with this antidepressant. The marked differences observed in behavior among these enzymes speaks to the importance of intrinsic structural differences between the active sites of copper amine oxidases (CAO) which affect reactivity with a given inhibitor.

Amine Oxidase (Copper-Containing)↗
PubMed2003

Optical sensor for amine vapors based on dimer-monomer equilibrium of indium(III) octaethylporphyrin in a polymeric film.

A novel transduction chemistry for the development of a polymer film-based optical sensor that responds reversibly to gas-phase amine species at sub-ppm levels is described. The sensor is based on the equilibrium of a indium(III) octaethylporphyrin hydroxide ion-bridged dimer species with corresponding monomeric porphyrins within a thin poly(vinyl chloride) film as a function of the level of volatile amine in the surrounding gas phase. The presence of amines causes the dimeric species to be converted to monomer via the ligation of the amine with the In(III) center of the porphyrin structure. This yields a significant change in the visible absorption spectrum of the film, with a decrease in the intensity of the Soret band corresponding to the dimer (lambdamax = 390 nm) and a concomitant increase in the Soret band for the monomer lambdamax = 406-408 nm). Response to different amines is based on their relative partition coefficient into the polymer film and their strength of axial ligation reactions, with a selectivity pattern of 1-butylamine > 1-propylamine > pyridine > triethylamine > ethylamine > methylamine > diethylamine > tert-butylamine > ammonia. It is further shown that a significant concentration of dimeric species within the polymer film can only be achieved if appropriate amounts of lipophilic anionic sites are also incorporated into the polymer in the form of a tetraphenylborate derivative and the resulting film is equilibrated briefly with water prior to gas-phase measurements. With optimized film compositions, 1-butylamine can be detected in the gas phase to levels approaching 0.1 ppm, while less lipophilic ammonia can be monitored down to 10 ppm, with fully reversible responses to each species. A simple mathematical model for the response of the amine sensor is presented and shown to predict the optical behavior observed.

Amines↗
PubMed2002

Selective detection of biogenic amines using capillary electrochromatography with an on-column derivatization technique.

A selective detection method for biogenic amines present in highly complex matrixes was devised by employing both electrokinetic injection and on-column-derivatization capillary electrochromatographic methods. The on-column derivatization capillary electrochromatography system was evaluated by use of a capillary column (total length of 45 cm, effective length of 25 cm) fabricated using a 100-mcirom (i.d.) fused-silica capillary tube packed with 5-microm (i.d.) ODS particles that were tolerant of an alkaline environment. The column was filled with a run buffer consisting of a derivatization reagent, o-phthalaldehyde/2-mercaptoethanol, in a mixture of borate buffer (pH 10). After electrokinetic injection of a mixture of five biogenic amines (histamine, serotonin, tyramine, putrescine, cadaverine) as a test sample, the free amines entered into the anodic site of the capillary column and started to travel along the column, during which time the analytes reacted with the derivatization reagent, separated out, and were detected with an absorbance at 340 nm when high voltage was applied to the column. When this system was applied to a mixture containing 5 biogenic amines and 17 amino acids, the 5 biogenic amines plus arginine selectively entered into the capillary with the electrokinetic injection and were observed on the electrochromatogram, but none of the amino acids lacking arginine were detected. The designated method was also tested for its ability to determine the presence of biogenic amines in the crude extracts obtained from two types of aged fish.

Acetonitriles↗
PubMed2003

On-line preconcentration prior to on-column derivatization monolith octadecasiloxane capillary electrochromatography for the determination of biogenic amines.

To expand the applications of the on-line preconcentration technique with capillary electrochromatography (CEC) to biogenic amines that have no specific chromophore or fluorophore in their molecules, a method of on-line preconcentration prior to on-column derivatization CEC is presented. A monolithic ODS capillary column (20 cm effective length x 75 microm i.d.) for CEC was fabricated using a thermal sol-gel reaction of tetraethyl orthosilicate to capture ODS particles (5-microm particle diameter) in a capillary tube. A standard model biogenic amine solution consisting of histamine, methylhistamine, and serotonin was electrokinetically injected from the anodic site of the capillary column with 5 kV, and these amines were effectively concentrated at the inlet site of the capillary column by a field-amplified sample stacking, a gradient effect mode, or both. This preconcentration occurred whenever the several types of solvent for reconstitution of the amines, e.g., water (noneluting solvent or low-conductivity solvent), 0.9% sodium chloride (noneluting solvent or high-conductivity solvent), or 60% acetonitrile in 10 mM borate buffer (pH 10) (eluting solvent) were employed. After concentration, the amines were subsequently derivatized, separated, and detected during CEC with an optimum CEC run buffer solution containing 60% acetonitrile in 5 mM o-phthalaldehyde/2-mercaptoethanol-10 mM borate buffer (pH 10) when 5 kV was continuously applied. Using the present system, equipped with a fluorescence detector instead of a UV/visible detector, the detection sensitivity for amines reached a 0.1 microM level, which increased sensitivity by a factor of 10(3) times greater than that of normal on-column derivatization CEC.

Biogenic Amines↗
PubMed2000

Role of lys100 in human dihydroorotate dehydrogenase: mutagenesis studies and chemical rescue by external amines.

Chemical modification, mutagenesis, chemical rescue, and isotope effect studies are used to identify and probe the roles of several conserved amino acid groups in catalysis by human dihydroorotate dehydrogenase. Time- and pH-dependent inactivation of human dihydroorotate dehydrogenase by trinitrobenzenesulfonate implicates at least one critical lysyl residue in catalysis. Of four highly conserved lysines, only the cognate of Lys255 was previously suggested to have catalytic functionality. We now show that replacement of either Lys184 or Lys186 by mutagenesis does not impact, whereas substitution of Lys100 abolishes, enzymatic activity. However, activity is partially restored to K100C (or K100A) by inclusion of exogenous primary amines in reaction mixtures. This rescued activity saturates with respect to numerous amines and exhibits a steric discrimination reflected in K(d,(amine)) values. For all amines, rescued k(cat) values were only approximately 10% of wild type and independent of amine basicity. K(M) values for dihydroorotate and coenzyme Q(0) were similar to wild type. Thus, exogenous amines (as surrogates for Lys100) apparently complement a chemical, not binding, step(s) of catalysis, which does not entail proton transfer. In support of this postulate, solvent kinetic isotope effect analysis indicates that Lys100 stabilizes developing negative charge on the isoalloxazine ring of flavin mononucleotide during hydride transfer, as has been observed for a number of flavoprotein oxidoreductases. Ser215 of human dihydroarotate dehydrogenase (DHODase) was also studied because of its alignment with the putative active-site base Cys130 of Lactococcus lactisDHODase. Substantial retention of activity by S215C, yet complete loss of activity for S215A, is consistent with Ser215 serving as the active-site base in the human enzyme.

Amines↗
PubMed1994

Copper amine oxidase: heterologous expression, purification, and characterization of an active enzyme in Saccharomyces cerevisiae.

A copper amine oxidase gene from a methylotrophic yeast Hansenula polymorpha has been expressed in Saccharomyces cerevisiae under the control of the ADHI promoter and the recombinant protein purified to near homogeneity. The recombinant enzyme is as active as the native enzyme in catalyzing methylamine oxidation. We demonstrate that it is a quinoprotein by redox-cycling staining and titrations with carbonyl reagents. The absorption spectral properties of the recombinant amine oxidase and its phenylhydrazine derivative are very similar to those of other copper amine oxidases. The cofactor in the enzyme is 2,4,5-trihydroxyphenylalanine (topa) quinone, as demonstrated by the pH-dependent shift in the lambda max of the p-nitrophenylhydrazone adduct. Alignment of an active-site peptide and DNA-derived protein sequences reveals a tyrosine residue as the precursor to topa quinone, consistent with findings with other copper amine oxidases. All evidence presented herein indicates that the heterologously expressed copper amine oxidase protein is processed posttranslationally in S. cerevisiae to form an active enzyme with an intact cofactor. This occurs despite an inability of S. cerevisiae to utilize amines as a nitrogen source. The implications of this study for the mechanism of topa quinone biogenesis are discussed.

Amine Oxidase (Copper-Containing)↗
PubMed1984

Kinetics of appearance of sulfhydryl groups in alpha 2-macroglobulin on reaction of the inhibitor with amines.

The mechanism of the appearance of sulfhydryl groups in alpha 2-macroglobulin in the reaction with amines was characterized by analyses of the kinetics with ammonia and methylamine. All reactions occurred under pseudo-first-order conditions in the range of pH (7.0-8.6) and amine concentration (10-600 mM) investigated. The logarithm of the pseudo-first-order rate constant increased linearly as a function of pH with a slope of unity, indicating that the unprotonated amine is the active species in the reaction. Plots of the observed pseudo-first-order rate constants vs. concentration of unprotonated amine at constant pH were also linear and gave second-order-rate constants of 0.32 and 13.8 M-1 s-1 for ammonia and methylamine, respectively, at pH 8.0; similar values were obtained at pH 8.6. Activation energies of 85 and 100 kJ mol-1 and activation entropies of 10 and 95 J K-1 mol-1 for ammonia and methylamine, respectively, were estimated from Arrhenius plots, suggesting that the higher reaction rate for methylamine is due primarily to a higher activation entropy. These results are consistent with the release of sulfhydryl groups being caused by a nucleophilic attack of the uncharged amine on a thio ester bond of alpha 2-macroglobulin in a bimolecular reaction occurring under pseudo-first-order conditions. The characteristics of the reaction suggest that the thio ester in each alpha 2-macroglobulin subunit reacts independently and equivalently with the amine and also that the thio ester bond cleavage initiates the reaction sequence leading to inactivation of the inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗
PubMed1986

Amine uptake into intact mast cell granules in vitro.

Histamine, the principal amine of rat peritoneal mast cells, is taken up into isolated granules with intact membranes. Uptake is pH- and concentration-dependent and is not stimulated by the addition of Mg2+-ATP. The saturable uptake has a Km of 91.1 microM and a Vmax of 95.4 pmol (mg of protein)-1 min-1. Uptake is abolished by 5 mM ammonium ion. 5-HT, the other endogenous amine of the granules, and dopamine and tyramine, which do not occur naturally in rat mast cells, each competitively inhibits [3H]-histamine uptake with Ki's close to 1 microM. Reserpine, a putative amine carrier blocker, inhibits uptake at nanomolar concentrations. At high concentrations, uptake of [3H]-5-HT is nonsaturable; at low concentrations, a saturable component is observed with a Km of 1.6 microM. Uptake of [3H]-5-HT is not enhanced by Mg2+-ATP. It is pH-dependent but with a lower apparent pKa than that of histamine. [3H]-5-HT uptake can be completely inhibited by ammonium ions. Amine inhibition of [3H]-5-HT gives nonlinear Dixon plots, and high concentrations of the competing amines or reserpine cannot completely block uptake. We propose a model consistent with these results in which amine uptake occurs by several distinct saturable transport systems. According to the model, histamine is transported by a single system, which also transports 5-HT and dopamine. 5-HT and dopamine are transported by one or more other systems.

Adenosine Triphosphate↗
PubMed1987

Mechanism of isomerization of 11-cis-retinal in lipid dispersions by aromatic amines.

It has previously been shown that retinotoxic, primary aromatic amines catalyze the isomerization of 11-cis-retinal to its all-trans congener after Schiff base formation [Bernstein, P.S., Fulton, B.S., & Rando, R.R. (1986) Biochemistry 25, 3370-3377]. This process led to the short-circuiting of the visual cycle and the observed retinotoxicity when it occurred in vivo. The catalysis was also observed to occur in vitro in phosphatidylcholine-based vesicles but not in hydrocarbon solutions. The rate of isomerization of an aromatic amine Schiff base of 11-cis-retinal in the phospholipid vesicles was typically 10(3)-fold more rapid than in hydrocarbon solutions. In this article, the mechanistic basis of this apparently membrane-specific catalysis is described. It was found that the rate enhancement effect observed was independent of the lipid used. Moreover, a bilayer structure was not important because rate enhancements were also observed in micelles. The rapid isomerization rates observed in lipid dispersions appear not be free radical initiated because free radical quenching agents, such as alpha-tocopherol and beta-carotene, had little effect on the isomerization rates. It was further found that aliphatic amines, such as n-dodecylamine, could be substituted for the aromatic amines in phospholipid. Finally, and most importantly, it was found that the isomerization of the aromatic amine retinal Schiff bases in phospholipid vesicles was acid-catalyzed. It is concluded that the rate enhancements observed for the isomerization of 11-cis-retinal-aromatic amine Schiff bases in lipid dispersions over that in hydrocarbon solvents are due to the occurrence of acid-base catalysis in the former.

Amines↗
PubMed2005

Biogenic amines in wines from three Spanish regions.

One hundred and sixty-three wines from La Rioja, Utiel-Requena, and Tarragona were analyzed to determine if there were any differences in the concentrations of six biogenic amines that are found in these three regions. The influence of grape variety, type of vinification, wine pH, malolactic fermentation, and storage in bottle on biogenic amine concentrations was studied. Results show important differences in putrescine and histamine concentrations among regions, varieties of grape, and type of wine; differences were less appreciable for the remaining biogenic amines studied. Low pH prevented biogenic amine formation. Malolactic fermentation and short storage periods in bottle (3-6 months) showed increases in histamine concentration, whereas longer periods of storage led to a general decrease in histamine. Several strains of lactic acid bacteria were isolated in this work, and their ability to form biogenic amines was assayed in synthetic media, grape must, and wine. Grape varieties, different types of winemaking, pH, and lactic acid bacteria may be responsible for the differences observed in the biogenic amine concentrations of the wines analyzed.

Biogenic Amines↗
PubMed2005

Protection of originality of Tokaji Aszú: amines and organic acids in botrytized wines by high-performance liquid chromatography.

Amine and organic acid composition of Aszú wines from the Tokaj region of Hungary, nonbotrytized Hungarian wines from different regions, and foreign botrytized wines were analyzed by high-performance liquid chromatography. Hungarian and foreign wines (36 Hungarian and seven foreign botrytized wines) were compared in different ways by calculation of ratios of given amine compounds, analyses of variance, principal component, and discriminant analysis. In wines, putrescine and in some samples 3-methyl-butylamine and/or phenyl ethylamine were found in remarkable concentrations, while in botrytized wines four other amines were verified in high concentration. Good separation between Aszú and foreign botrytized wines was found by calculation of the amine component's ratio. The first two principal components of the principal component analysis accounted for 77 and 84% of the total variance in the data of amines and acids, respectively. The component scores of samples grouped according to Aszú, foreign botrytized, and nonbotrytized wines. Linear discriminant analysis was used for differentiation of Aszú, foreign botrytized, and normal wines. Using nine amines and two acids as variables, the correct classification was 97.6%. On the basis of results, an objective evaluation method can be elaborated for quality control in order to protect the authenticity and origin of wine specialties made from botrytized grapes.

Acids↗
PubMed2006

Amine degradation by 4,5-epoxy-2-decenal in model systems.

The reactions of 4,5-epoxy-2-decenal with octylamine, benzylamine, and 2-phenylglycine methyl ester were studied to investigate if amines may suffer a Strecker type degradation by epoxyalkenals analogously to amino acids. In addition to other reactions, the studied amines were converted into their corresponding Strecker aldehydes (octanal, benzaldehyde, and methyl 2-oxo-2-phenylacetate, respectively) to an extent that depended on the pH, the temperature, the amount of epoxyalkenal, and the amine involved. Each amine exhibited an optimum pH for the reaction, but the corresponding Strecker aldehydes were produced to a significant extent within a broad pH range. In addition, the temperature mostly influenced the reaction rate, which was increased between 6.5 and 9.5 times when the reaction was carried out at 60 degrees C than when it took place at 37 degrees C. Furthermore, Strecker aldehyde formation was linearly correlated with the amount of the epoxyalkenal present in the reaction mixture. Nevertheless, the reaction yield mostly depended on the amine involved. Thus, octylamine only produced trace amounts of octanal, benzylamine was converted into benzaldehyde with a yield of 4.3%, and 2-phenylglycine methyl ester was converted into methyl 2-oxo-2-phenylacetate with a reaction yield of 49%. All of these results suggest that suitable amines can be degraded by epoxyalkenals to their corresponding Strecker aldehydes to a significant extent.

Aldehydes↗
PubMed1999

Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings.

Mixtures of amino acids, creatine, and glucose simulating the composition of six different kinds of meats (beef, chicken breast, chicken thigh, turkey breast, pork, and fish) were dry-heated to simulate the formation of heterocyclic amines in meats. The presence of 16 heterocyclic amines was investigated in the model systems and in the six meats and their corresponding meat drippings to determine the importance of meat composition to heterocyclic amine formation. Nine mutagenic amines (IQ, MeIQ, 8-MeIQx, 4,8-DiMeIQx, PhIP, IQx, IFP, DMIP, and TMIP) were found to be present at concentrations >0.1 ng/g in some of the model systems and in some of the meats or pan residues. Heterocyclic amine concentrations clearly are affected by precursor composition in this model system, and the same nine heterocyclic amines formed in the meat and in the model system show that this is a well-controlled surrogate for the reaction conditions that occur in meats during cooking.

Amines↗
PubMed2002

Cesium effect: high chemoselectivity in direct N-alkylation of amines.

A novel method for the mono-N-alkylation of primary amines, diamines, and polyamines was developed using cesium bases in order to prepare secondary amines efficiently. A cesium base not only promoted alkylation of primary amines but also suppressed overalkylations of the produced secondary amines. Various amines, alkyl bromides, and alkyl sulfonates were examined, and the results demonstrated this methodology was highly chemoselective to favor mono-N-alkylation over dialkylation. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the secondary amines exclusively, offering wide applications in peptidomimetic syntheses.

Alkylation↗
PubMed2005

Catalytic reductive alkylation of secondary amine with aldehyde and silane by an iridium compound.

[reaction: see text] An efficient methodology for the reductive alkylation of secondary amine with aldehyde and Et(3)SiH using an iridium complex as a catalyst has been developed. For example, treatment of dibutylamine with butyraldehyde and Et(3)SiH (a 1:1:1 molar amount of amine, aldehyde, and silane) in 1,4-dioxane at 75 degrees C under the influence of a catalytic amount of [IrCl(cod)](2) gave tributylamine in quantitative yield. In this reaction, no reduction of aldehyde took place. It was found that IrCl(3), which is a starting material for preparation of iridium complexes such as [IrCl(cod)](2), acts as an efficient catalyst for the present reductive alkylation of amine. In addition, a cheaper, easy-to-handle, and environmentally friendly reducing reagent such as polymethylhydrosiloxane (PMHS) in place of Et(3)SiH was also useful. Thus, a variety of secondary amines could be alkylated by allowing them to react with aldehydes and PMHS in the presence of an iridium catalyst to afford the corresponding tertiary amines in good to excellent yields. From the deuterium label experiments, it was revealed that silane and water, generated during the formation of enamine by the reaction of amine and aldehyde, seem to behave as a hydrogen source. The catalytic cycle was discussed.

Aldehydes↗
PubMed2005

Azulene-substituted aromatic amines. synthesis and amphoteric redox behavior of N,N-Di(6-azulenyl)-p-toluidine and N,N,N',N'-tetra(6-azulenyl)-p-phenylenediamine and their derivatives.

[reaction: see text] N,N-Di(6-azulenyl)-p-toluidine (1a) and N,N,N',N'-tetra(6-azulenyl)-p-phenylenediamine (2a) and their derivatives with 1,3-bis(ethoxycarbonyl) substituents on each 6-azulenyl group (1b and 2b) were prepared by Pd-catalyzed amine azulenylation and characterized as a study into new aromatic amines for multistage amphoteric redox materials. The redox behavior of each compound was characterized by cyclic voltammetry. These compounds undergo facile reduction to stable anion radicals and dianion diradicals owing to the resonance stabilization between the 6-azulenyl groups and exhibit electrochemical oxidation depending on the amine subunits. The ESR measurement of anion radicals and a dianion diradical generated by the electrochemical reduction of amine 1b and diamine 2b revealed that the unpaired electron of these radicals delocalizes over the entire azulene ring including the central nitrogen atoms. UV-vis spectral analysis of amines 1a,b and diamines 2a,b, taken during the electrochemical reduction, exhibited a gradual decrease of the absorption bands of the neutral species along with an increase of the new absorption maxima at 625, 605, 640, and 610 nm, respectively, with the development of well-defined isosbestic points at 502, 562, 478, and 545 nm, respectively. As indicated by a combined ESR and UV-vis spectral study, the species giving rise to the new absorption maxima are concluded to be the generation of anion radicals and dianion diradicals of aromatic amines and diamines with high thermodynamic stability.

Amines↗
PubMed2006

Mechanisms of amine-catalyzed organosilicate hydrolysis at circum-neutral pH.

Mono- and polyamines can catalyze the hydrolysis and condensation of organosilicate starting materials in biomimetic silica synthesis pathways at circum-neutral pHs and room temperature. Our study is focused on understanding the mechanistic role of amines in catalyzing the hydrolysis process that precedes condensation. We have conducted (29)Si NMR experimental studies over a range of temperature and pHs for the hydrolysis rates of trimethylethoxysilane (TMES), a model compound with only one hydrolyzable bond, combined with quantum mechanical hybrid density functional theory calculations of putative intermediate and transition-state structures for TMES and tetramethyl orthosilicate (TMOS). Comparison of calculated energies with experimentally determined activation energies indicates that amine catalysis of TMES is primarily a consequence of the amine's acidity at neutral pH. The proton released by the amine is transferred to the organosilicate, producing a protonated ethoxy leaving group that can be displaced by water in an S(N)2 reaction. For TMOS, the activation energy of proton-transfer coupled with S(N)2 substitution is comparable to that for Corriu's nucleophile-activated nucleophilic displacement, such that the mechanism of amine-catalyzed hydrolysis is dependent mostly on the ambient pH conditions as well as the type of amine. The relevance of our results to biological silica precipitation is discussed.

Amines↗