Ildiko M Kovach

Ildiko M Kovach
Catholic University of America | CUA · Department of Chemistry

PhD

About

85
Publications
1,976
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,385
Citations
Additional affiliations
September 1989 - August 2011
Catholic University of America
January 1975 - August 1989
University of Kansas

Publications

Publications (85)
Article
Full-text available
Inquiries into the participation of short hydrogen bonds in stabilizing transition states and intermediate states in the thrombin, factor Xa, plasmin and activated protein C–catalyzed reactions revealed that specific binding of effectors at Sn, n = 1–4 and S’n, n = 1–3 and at remote exosites elicit complex patterns of hydrogen bonding and involve w...
Article
Full-text available
Pdr5 is the founding member of a large subfamily of evolutionarily distinct, clinically important fungal ABC transporters containing a characteristic, deviant ATP-binding site with altered Walker A, Walker B, Signature (C-loop), and Q-loop residues. In contrast to these motifs, the D-loops of the two ATP-binding sites have similar sequences, includ...
Article
Full-text available
Thrombin is the pivotal serine protease enzyme in the blood cascade system and thus a target of drug design for control of its activity. The most efficient non-physiologic inhibitor of thrombin is hirudin, a naturally occurring small protein. Hirudin and its synthetic mimics employ a range of hydrogen bonding, salt bridging and hydrophobic interact...
Article
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Article
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Article
Thrombin is the pivotal serine protease enzyme in the blood cascade system. Phe-Pro-Arg-chloromethylketone (PPACK), phosphate, and phosphonate ester inhibitors form a covalent bond with the active-site Ser of thrombin. PPACK, a mechanism-based inhibitor, and the phosphate/phosphonate esters form adducts that mimic intermediates formed in reactions...
Article
Hydrolytic reactions of oligopeptide 4-nitroanilides catalyzed by human-alpha-thrombin, human activated protein C and human factor Xa were studied at pH 8.0-8.4 and 25.0+/-0.1 degrees C by the progress curve method and individual rate constants were calculated mostly within 10% internal error using DYNAFITV. A systematic strategy has been developed...
Article
The stereoselectivity of phosphonylation of serine hydrolases by the ROR'P(O)X group of compounds is governed by the electronic properties of X and the size of RO. The electronic properties of ligands attached to P are decisive in whether C-O or P-O bond cleavage occurs in phosphonate diesters of serine hydrolases. Phenolate ions leave readily with...
Article
Kinetic solvent isotope effects (KSIEs) for the factor Xa (FXa)-catalyzed activation of prothrombin in the presence and absence of factor Va (FVa) and 5.0 x 10(-5) M phospholipid vesicles are slightly inverse, 0.82-0.93, when substrate concentrations are at 0.2 Km. This is consistent with the rate-determining association of the enzyme-prothrombin a...
Article
Proton inventory studies of the thrombin-catalyzed fibrinogen activation to fibrinopeptide A are most consistent with a two-proton bridge forming at the transition state probably between Ser195 OgammaH and His57 Nepsilon2 and His57 Ndelta1 and Asp102 COObeta- at the active site, with fractionation factors 0.66 +/- 0.03 under enzyme saturation with...
Article
The stereoselectivity of phosphonylation of serine hydrolases by the ROR′P(O)X group of compounds is governed by the electronic properties of X, the size of RO groups, the active site milieu and the specific architecture of the active site of the serine hydrolase. For example, stereoselectivity in excess of 104 has been observed favoring the P(S) d...
Article
Deuterium kinetic solvent isotope effects for the human alpha-thrombin-catalyzed hydrolysis of (1) substrates with selected P(1)-P(3) sites, Z-Pro-Arg-7-amido-4-methylcoumarin (7-AMC), N-t-Boc-Val-Pro-Arg-7-AMC, Bz-Phe-Val-Arg-4-nitroanilide (pNA), and H-D-Phe-L-Pip-Arg-pNA, are (DOD)k(cat) = (2.8-3.3) +/- 0.1 and (DOD)(k(cat)/K(m)) = (0.8-2.1) +/-...
Article
The lengths of short, strong hydrogen bonds (SSHBs) on enzymes have been determined with high precision (±0.05 Å) from the chemical shifts (δ), and independently from the D/H fractionation factors (φ) of the highly deshielded protons involved. These H-bond lengths agree well with each other and with those found by protein X-ray crystallography, wit...
Article
Seven new aryl methyl g -ketophosphonate esters were synthesized. The hydrolytic rates of the compounds under physiological conditions were studied. Most of the compounds are effective inhibitors of acetylcholinesterase. The enzyme recovers on the 10-50 h time scale from its adducts with two of the inhibitors.
Article
Facile and highly enantioselective synthesis of 4-nitrophenyl alkyl methylphosphonothioates 5a–f was achieved in high yields via BF3·Et2O-catalyzed alcoholysis of resolved phosphonamidothioates 4a and 4b.
Article
Activation parameters for the imidazole-catalyzed hydrolysis of bis(4-nitrophenyl) methylphosphonate (NMN) are ΔH‡ = 44 ± 2 (H2O) and 46 ± 2 (D2O) kJ/mol and ΔS‡ = -146 ± 5 (H2O) and -145 ± 5 (D2O) J/mol K. The activation parameters for water-catalyzed hydrolysis of NMN in H2O are ΔH‡ = 28 ± 10 kJ/mol and ΔS‡ = -270 ± 30 J/mol K. The solvent isotop...
Article
4-Nitrophenyl 4-substituted-phenacyl methylphosphonate esters (CH3, H, CH3O, NO2, and Cl) decompose in aqueous buffers 1-4 orders of magnitude faster than analogs with alkoxy substituents not containing a β-carbonyl group. This is consistent with an intramolecular displacement of 4-nitrophenol by the anion of the carbonyl hydrate. 18O incorporation...
Article
β-Deuterium secondary isotope effects for the phosphonylation of the active site serine of acetylcholinesterase (AChE) by phosphonyl derivatives at 25°C and pH 7.70 in 0.05 M phosphate buffer were as follows: 3,3-dimethyl-2-butyl methylphosphonofluoridate (soman), 0.90 ± 0.03; 2-propyl methylphosphonofluoridate (sarin), 0.91 ± 0.04; 4-nitrophenyl 2...
Article
3,3-Dimethyl-2-butyl methylphosphonofluoridate (soman) recruits at least 60-70% of the catalytic power of acetylcholinesterase during phosphonylation of the active-site serine, as compared with the acetylation by acetylcholine. The solvent isotope effect is 1.34 +/- 0.11 and is temperature independent within experimental error between 5 and 45°C....
Article
Proton inventories (determination of kinetic parameters in binary mixtures of protium and deuterium oxides) for the action of acetylcholinesterases on phenyl acetate indicate that the overall solvent isotope effect of 2.42 ± 0.03 (electric-eel enzyme), or 2.28 ± 0.11 (erythrocyte enzyme), on kcat arises from a single site in the transition state. T...
Article
The reaction of phenyl acetate (CH3CO2C6H5 and CD3CO2C6H5) with methoxyamine at 25°C in water exhibits β-secondary deuterium isotope effects k3H/k3D of 0.857 ± 0.024 (general-acid catalysis by CH3O2CCH2CH(CO2CH 3)NH3+, kHOH/kDOD = 3.9 ± 0.8) and 0.867 ± 0.009 (general-acid catalysis by CH3ONH3+, kHOH/kDOD = 1.75 ± 0.06). These values are consistent...
Article
β-Deuterium and β-tritium isotope effects on phase transfer equilibria between water and cyclohexane or chlorocyclohexane were determined for acetone and p-nitroacetanilide spectrophotometrically and for acetone and ethyl acetate by a dual-label radioactive isotopic technique. Results of all measurements yield 1-2% normal (protium favored in the or...
Article
Model calculations of the ¹H/²H, ¹²C/¹³C, and ¹⁶O/¹⁸O kinetic and equilibrium isotope effects at the starred positions for the carbonyl addition reaction of Hâ/sup */CC*H*O* with HO/sup *-/ have been made for two closely related sets of force fields, and for both curved and perpendicular trajectories of nucleophilic approach to carbonyl...
Article
β-Deuterium isotope effects (β-DIE) determined in acetonitrile for the following reactions are: CH3COO- + 4-NO2C6H4O2CCL3 (L = H, D) (PNPA-L3), 0.958 ± 0.007 (5-45°C); CH3COO- + 2,4-(NO2)2C6H3O2CCL 3 (DNPA-L3), 0.964 ± 0.011 (5-20°C); OH- + PNPA-L3, 0.972 ± 0.028 (25°C); 4-NO2C6H4O- (PNP-) + CL3COOCOCL3, 1.00 ± 0.02 (20°C); 4-NO-C6H4O- (PNOP-) + CL...
Article
Cholinesterases use a Glu-His-Ser catalytic triad to enhance the nucleophilicity of the catalytic serine. We have previously shown by proton NMR that horse serum butyryl cholinesterase, like serine proteases, forms a short, strong hydrogen bond (SSHB) between the Glu-His pair upon binding mechanism-based inhibitors, which form tetrahedral adducts,...
Article
Full-text available
The role of active-site residues in the dealkylation reaction in the P(S)C(S) diastereomer of 2-(3,3-dimethylbutyl)methylphosphonofluoridate (soman)-inhibited Torpedo californica acetylcholinesterase (AChE) was investigated by full-scale molecular dynamics simulations using CHARMM: >400 ps equilibration was followed by 150-200 ps production runs wi...
Article
Cholinesterases (ChE), use a Glu-His-Ser catalytic triad to enhance the nucleophilicity of the catalytic serine. It has been shown that serine proteases, which employ an Asp-His-Ser catalytic triad for optimal catalytic efficiency, decrease the hydrogen bonding distance between the Asp-His pair to form a short, strong hydrogen bond (SSHB) upon bind...
Article
Enantiomers of 4-nitrophenyl 4-X-phenacyl methylphosphonate esters (X = H, PMN; CH3 and CH3O) inactivate human factor Xa with rate constants 8-86 M(-1)s(-1) at pH 6.75 in 0.025 M Hepes buffer, 0.15 M NaCl and 2 mM CaCl2 at 7.0+/-0.1 degrees C. The stereoselectivity of the inactivation of factor Xa is 2-10 and favors the levorotatory enantiomers. Th...
Article
Product analysis of dealkylation in P(S)C(S)-soman-inhibited electric eel acetylcholinesterase (AChE) by GC-MS using the selected ion monitoring mode has been carried out. The instrument was calibrated with pure standards of 2,3-dimethyl-1-butene and 2, 3-dimethyl-2-butene in the gas phase and methylene chloride extracts of 2,3-dimethyl-2-butanol a...
Article
Bimolecular rate constants for the inactivation of recombinant (r) human (Hu) butyrylcholinesterase (BChE) with P(S)C(S)- and P(S)C(R)-2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman) are (92 +/- 7) x 10(6) M-1 min-1 and (13.7 +/- 0.8) x 10(6) M-1 min-1 at pH 7.4, mu = 0.1 M and 25 degreesC. Mutations of E197(199) to D or Q and W82(84) to A...
Article
Two competing passageways for the exit of acetic acid and acetate ion in Torpedo californica (Tc) acetylcholinesterase (ACHE) were studied by examining free energies of passage through two potential trajectories using the umbrella sampling technique as implemented in CHARMM. The coordinates for migration were defined as the distance from Ser200 Oγ,...
Article
Chymotrypsin and subtilisin BPN‘ can be inhibited by bis(4-nitrophenyl) methylphosphonate (NMN) and bis(4-nitrophenyl) propylphosphonate (NPN) very efficiently with second-order rate constants, ki/Ki, between 544 and 4300 M-1 s-1 at 25.0 ± 0.1 °C at the pH maxima. The second-order rate constants for the inhibition of trypsin are 26.3 ± 1.4 M-1 s-1...
Chapter
The pH-dependence and solvent isotope effects of dealkylation in diastereomeric adducts of Electric eel (Ee) acetylcholinesterase (AChE), fetal bovine serum (FBS) AChE (1), mouse (Mo) AChE and human (Hu) butyrylcholinesterase (BChE) inactivated with P(S)C(S) and P(S)C(R) 2-(3, 3-dimethylbutyl) methylphosphonofluoridate (soman) were studied at 25.0...
Chapter
Mechanistic studies of the early phases of the inactivation of cholinesterases (ChEs) by 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman) were carried out in this laboratory and the results of these studies were reported in a series of papers. The main conclusions were reviewed in an article (1) in which the underlying reason for the irrever...
Article
Enantiomers of 4-nitrophenyl 4-X-phenacyl methylphosphonate esters (X = H, PMN; CH3; and CH3O) inactivate human alpha-thrombin with rate constants 4-235 M-1 s-1 in pH 6.5, 0.025 M citrate buffer, and 0.15 M NaCl at 7.0 +/- 0.1 degrees C. Stereoselectivity of the inactivation of thrombin is 2-39 and favors the levorotatory enantiomers. The pH-depend...
Article
The pH-dependence and solvent isotope effects of dealkylation in diastereomeric adducts of Electric eel (Ee) and fetal bovine serum (FBS) acetylcholinesterase (AChE) inactivated with P(-)C(+) and P(-)C(-) 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman) were studied at 4.0 +/- 0.2 degrees C. The rate constant versus pH profiles were fit to a...
Article
Molecular dynamics (MD) simulations using CHARMM were performed for the solution structures of the pentacoordinate and tetracoordinate PSCS and PRCS adducts of Torpedo californica (Tc) acetylcholinesterase (AChE) formed with 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman) to assess the molecular origins of stereoselectivity of phosphonylati...
Article
In spite of their rapid aqueous hydrolysis, 4-nitrophenyl 4-X-phenacyl methylphosphonates (X = H, (PMN) CH3, CH3O, Cl and NO2) inactivate many serine proteases of the pancreatic and blood coagulation systems efficiently. The rate constants, K/Ki, for the inactivation of tissue-type plasminogen activator enzyme (t-PA) are 470-750 M-1 S-1 with PMN, 4...
Article
The stabilizing interactions in pentavalent and tetravalent phosphonate esters of the active-site Ser in selected serine hydrolase enzymes can be used to explain how these man-made molecules recruit enzyme catalytic power up to 70% of that of the natural substrate. The removal of the leaving group of a substrate or inhibitor is very efficient by ac...
Article
The stabilizing interactions in pentavalent and tetravalent phosphonate esters of the active-site Ser in selected serine hydrolase enzymes can be used to explain how these man-made molecules recruit enzyme catalytic power up to 70% of that of the natural substrate. The removal of the leaving group of a substrate or inhibitor is very efficient by ac...
Article
Molecular mechanics and dynamics combined with semiempirical calculations were carried out for purposes of comparison of the active site characteristics of AChE, trypsin, and chymotrypsin as probed by their diastereomeric adducts with 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman), methylphosphonate monoester anions, and tetravalent carbon...
Article
The aging reaction from the adducts of electric eel (EE) and fetal bovine serum (FBS) acetyicholinesterase (AChE) with soman P(-)C(-) and P(-)C(+) show a bell-shaped pH-rate profile. The aging of soman and sarin are specific acid catalyzed and show small (1.1 - 1.6) solvent isotope effects. These results and molecular mechanics calculations support...
Chapter
Covalently bonded inhibitors of serine hydrolases have been considered to be good probes of the characteristics of the active site. Organophosphorus compounds (OP) and activated ketones are most prominent in this context because they should mimick the geometry of the transition state(s) of the reaction of the natural substrate.
Article
Huperzine A, a potential agent for therapy in Alzheimer's disease and for prophylaxis of organophosphate toxicity, has recently been characterized as a reversible inhibitor of cholinesterases. To examine the specificity of this novel compound in more detail, we have examined the interaction of the 2 stereoisomers of Huperzine A with cholinesterases...
Article
The channels connecting the active site of acetylcholinesterase (AChE) to the protein exterior were mapped by computational techniques in order to find potential exit routes for charged reaction products. 3.9% of the total volume of the AChE monomer is hollow space and over 50% of the void is located in the center; it is partitioned into three cham...
Article
Trypsin is inactivated by the levorotatory enantiomers (most likely PS) of 4-nitrophenyl 4-H-, 4-CH3-,4-OCH3-, and 4-Cl-phenacyl methylphosphonates (PMNs) with second-order rate constants between 231 and 884 M-1 s-1. 4-NO2-PMN hydrolyzes before inhibiting the enzyme. The second-order rate constants for the inactivation of alpha-chymotrypsin by the...
Article
Trypsin is inactivated by the levorotatory enantiomers (most likely P-S) of 4-nitrophenyl 4-H-, 4-CH3-, 4-OCH3-, and 4-Cl-phenacyl methylphosphonates (PMNs) with second-order rate constants between 231 and 884 M(-1) s(-1). 4-NO2-PMN hydrolyzes before inhibiting the enzyme. The second-order rate constants for the inactivation of a-chymotrypsin by th...
Article
Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3) using the X-ray coordinates for acetylcholinesterase (AChE) from Torpedo californica indicate electrostatic stabilization by the active site, Glu-199, of the developing positive charge on the incipient carbonium ion in the dealkylation in the adducts of AChE with PSCR a...
Article
Huperzine-A, a potential drug for the treatment of Alzheimer's disease and possible pretreament for nerve agent toxicity, has recently been characterized as a reversible inhibitor of cholinesterases (Ashani et al., BBRC, 184:719-726, 1992). Long-term incubation of purified cholinesterases with Huperzine-A did not show any chemical modification of H...
Article
The character of buffer-catalyzed hydrolysis of four phosphonates, bis-(4-nitrophenyl) methylphosphonate (NMN), 4-nitrophenyl 2-propyl methylphosphonate (IMN), 2-(3,3-dimethyl)butyl methylphosphonofluoridate (soman), and 4-nitrophenyl4-methylphenacyl methylphosphonate (MPMN), was investigated. The latter hydrolyzes by an intramolecular nucleophilic...
Article
Generation of diastereomeric phosphonate ester adducts of chymotrypsin was evidenced for the first time by 31P NMR and spectrophotometric kinetic measurements. 31P NMR signals were recorded for 4-nitrophenyl 2-propyl methylphosphonate (IMN) at 32.2 ppm and for its hydrolysis product at 26.3 ppm downfield from phosphoric acid. The inhibition of alph...
Article
Temporary modification of serine hydrolase activity with 4-nitrophenyl phenacyl and 4-nitrophenacyl methylphosphonates occurs with self-catalyzed intramolecular reactivation of chymotrypsin, trypsin, thrombin and plasmin
Article
A comparative study was carried out using various computational methods for phosphate and phosphonate esters as probes of the catalytic potentials and strategies of serine hydrolase enzymes. The semiempirical method MNDO, as implemented in MOPAC 5.0, was used for the generation of partial atomic charges for phosphate and phosphonate ester structure...
Article
Rapid irreversible inhibition of enzymes constitutes a difficult problem and demands sophisticated techniques to meet contemporary expectations of accuracy and precision. Modern computerized, analytical techniques now allow inhibition to be measured in the presence of a chromogenic substrate, the decomposition product of which can be followed by a...
Article
Two diastereomers (PR, PS) of 2-propyl methylphosphonate covalently bonded to Ser-195 of bovine trypsin have been generated from appropriate X-ray crystallographic coordinates. The corresponding enzymic dealkylation product, the methylphosphonate anion, has also been modeled for each diastereomer. In addition to 168 experimentally determined water...
Article
Solvent isotope effects have been measured for the reactions of 4-nitrophenyl 2-propyl methylphosphonate (IMN) with acetylcholinesterase (AChE), chymotrypsin, imidazole base, hydroxide ion, phosphate dianion, and water, and for the reactions of 2-propyl methyl phosphonofluoridate (sarin) with AChE. Kinetics and structural features of the dealkylati...
Article
Subtilisin BPN′ catalyzes the hydrolysis in protium and deuterium oxides of p-NO2C6H4OCOCL2NHCO2CH2C6H5(L = H, D) in the pH(D) range 5·0–8·5 (H2O) and 5·4–9·0 (D2O), according to simple Michaelis–Menten kinetics. The parameter kcat/Km exhibits pH(D) inflection points of 7·17 ± 0·05 (H2O) and 7·69 ± 0·08 (D2O), and kcat shows 6·88 ± 0·05 (H2O) and 7...
Article
Intact S-soman at 0.5–13 μM and S- and R-sarin at 50–100 μM in aqueous solutions were determined by a spectrofluorometric method, which detects chymotrypsin before and after its reaction with either inhibitor and the difference in active-site concentration measures concentration of the inhibitor. The chymotryptic method of analysis of organophospha...
Article
Energies of interactions for trypsin adducts phosphorylated at the active-site Ser-195, seryl 2-propylphosphate anion, with and without a proton on His-57 at the active-site, and seryl diisopropylphosphate with the protonated His-57 were calculated with the molecular mechanics program YETI. The total energy of stabilization is similar for the adduc...
Article
The structural profile for the interactions between serine proteases and organophosphorus (OP) compounds can be deduced from recent NMR and X-ray crystallographic data. Using the rationale proposed for serine proteases, dynamic data on the inhibition of acetylcholinesterase by OP compounds is also consistent with structural constraints and an impai...
Article
Full-text available
The major findings from the overall study are the following: Organophosphorus (OP) compounds recruit the full one-proton catalytic potential of acetylcholinesterase (AChE) in the course of the inhibition stage. AChE was found in the course of this research to be distinct from the serine proteases in possessing only a one-proton catalytic entity. Th...
Article
Molecular details for the recruitment of enzyme catalytic power in the inhibition of six serine hydrolases and two organophosphorus reagents have been investigated. The enzymes are: acetylcholinesterase (AChE) (eel); AChE (RBC); α-chymotrypsin; β-trypsin; elastase (PPE); subtilisin (BPN'). The agents are methyl 4-nitrophenyl propylphosphonate (MPN)...
Article
Proton inventories (determination of kinetic parameters in binary mixtures of protium and deuterium oxides) for the action of acetylcholinesterases on phenyl acetate indicate that the overall solvent isotope effects measured for two enzymes (electric-eel enzyme and erythrocyte enzyme) on k", arises from a single site in the transition state.
Article
Two new inhibitors, bis(4-nitrophenyl) propylphosphonate (NPN) and methyl 4-nitrophenyl propylphosphonate (MPN), react irreversibly with the serine proteases bovine pancreatic α-chymotrypsin (EC 3.4.21.1), porcine pancreatic elastase (EC 3.4.21.11), and subtilisin (EC 3.4.21.3) (NPN also reacts with bovine pancreatic trypsin (EC 3.4.21.4)) to liber...
Article
The reaction of CH; - CO - O - Ph and CD; - CO - O - Ph with methoxyamine (25°C, H2O) exhibits km/kw of 0.857 i 0.024 (general-acid catalysis [= gac] by MeOOC - CHZ- CH[COOMe]NH5 , kHOH/kDOD = 3.9 i 0.8) and 0.867 i 0.009 (gac by MeONHf , kHOH/kDOD = 1.75 i 0.06), consistent with rate-limiting proton transfer from general acid to a zwitterionic tet...
Article
Absorbance data were collected at three wavelengths for different mixtures of acetonitrile solutions of acetic acid and substituted phenolates in order to define ionic equilibria. Formation of hydrogen bonded adducts between acid and phenolate in concentration-dependent stoichlometry renders the data, even from very dilute solutions, too complex fo...
Article
Aus den Trichloressigs?urephenylestern (I) erh?lt man mit Kalium-acetat (II) die Phenolate (III) neben dem gemischten Anhydrid (IV).
Article
The fraction of tetrahedral character at the transition state (TS) deduced from ..beta..-deuterium isotope effects (..beta..-DIEs) for reactions of CH/sub 3/COO/sup -/ + PNPA is 0.32 in both CH/sub 3/CN and benzene, of CH/sub 3/CO/sup -/ + CNPA is 0.28 in CH/sub 3/CN and 0.12 in benzene, and of OH/sup -/ + PNPA is 0.21 in CH/sub 3/CN. These values...
Article
Tritium and 14C-labeled isomers of ethyl acetate are excellent substrates for competitive dual-labeled radioactive isotopic measurements of β-deuterium and β-tritium isotope effects. Methods are given for preparation of the ethyl esters of acetic acid-2-3H, acetic acid-2-14C, and acetic acid-2,2-2H2-2-3H, and of the acetic acid ester of ethanol-l-1...
Article
pH-rate profiles were calculated for the hydrolysis of the glycine (II), β-aspartic acid (III), and α-aspartic acid (IV) esters of p-acetamidophenol (I) at 25° and μ = 1.0 M. The hydrolysis of esters II and III occurred predominantly via intermolecular reactions involving water, hydroxide ion, and the various ionic forms of the substrates. The hydr...
Article
β-Deuterium isotope effect (β-DIE) studies of acyl transfer from aryl acetates to acetate ion in acetonitrile indicate the degree of tetrahedral character at the transition state (TS) to be small, and the same as in protic solvents.
Article
The anomalous temperature dependence of the ..beta..-deuterium (..beta..-D) secondary isotope effect reported by Halevi and Margolin for the hydroxide-promoted hydrolysis of ethyl acetate has been observed also with methyl acetate (CHâCOâCHâ vs. CDâCOâCHâ:k/sub 3H/k/sub 3D/ = 1.01 +- 0.02 (0°C), 0.90 +- 0.02 (25°C), 1.03 +- 0.10 (50°C)). In cont...
Article
β-Deuterium isotope effects (kCH3/kCD3) at 25°C in aqueous solution for reaction of the following nucleophiles and substrate acetate esters are as follows: CH3CO2-, 2,4-(NO2)2C6H3O2CCL 3 (L = H, D), 0.950 ± 0.008; C6H5O-, 4-NO2C6H4O2CCL3, 0.971 ± 0.020; C6H5O-, 2,4-(NO2)2C6H4O2CCL 3, 0.968 ± 0.009; HO-, 4-NO2C6H4O2CCl3, 0.970 ± 0.009; HO-, C6H5O2CC...
Article
The reactivity, solvent isotope effects, and proton inventory studies of the inhibition of AChE in comparison with chymotrypsin by soman (GD) and two newly synthesized compounds, methyl p-nitrophenyl n-propylphosphonate (MPPP) and bis p-nitrophenyl n-propylphosphonate (BPPP) is reported here. Bimolecular inhibition rates were observed. Methoxide di...
Article
Thesis (Ph. D.)--University of Kansas, Pharmaceutical Chemistry, 1974. Includes bibliographies.

Network

Cited By