The Free Energies of Hydrlysis of Some Esters and Thiol Esters of Acetic Acid

Jencks, William P.; Gilchrist, Mary.

doi:10.1021/ja01075a026

Cited by 55 publications

(39 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This calculated reaction free energy agrees reasonably well with the experimental free energy of ATP hydrolysis to AMP and PP i reported by Jencks (−7.7 kcal/mol, pH 7) 45 and Schuegraf (−10.3 kcal/mol, pH 7.5). 46 …”

Section: Resultssupporting

confidence: 89%

Quantum Mechanical Analysis of Nonenzymatic Nucleotidyl Transfer Reactions: Kinetic and Thermodynamic Effects of β–γ Bridging Groups of dNTP Substrates

2014

View full text Add to dashboard Cite

Rate (k) and equilibrium (K) constants for the reaction of tetrahydrofuranol with a series of Mg2+ complexes of methyl triphosphate analogues, CH3O-P(O2)-O-P(O2)-X-PO34–, X = O, CH2, CHCH3, C(CH3)2, CFCH3, CHF, CHCl, CHBr, CFCl, CF2, CCl2, and CBr2, forming phosphate diester and pyrophosphate or bisphosphonate in aqueous solution were evaluated by B3LYP/TZVP//HF/6-31G* quantum chemical calculations and Langevin dipoles and polarized continuum solvation models. The calculated log k and log K values were found to depend linearly on the experimental pKa4 of the conjugate acid of the corresponding pyrophosphate or bisphosphonate leaving group. The calculated slopes of these Brønsted linear free energy relationships were βlg = −0.89 and βeq = −0.93, respectively. The studied compounds also followed the linear relationship Δlog k = 0.8Δlog K, which became less steep, Δlog k = 0.6Δlog K, after the range of studied compounds was extended to include analogues that were doubly protonated on γ-phosphate, CH3O-P(O2)-O-P(O2)-X-PO3H22–. The scissile Pα–Olg bond length in studied methyl triphosphate analogues slightly increases with decreasing pKa of the leaving group; concomitantly, the CH3OPα(O2) moiety becomes more positive. These structural effects indicate that substituents with low pKa can facilitate both Pα–Olg bond breaking and the Pα–Onuc bond forming process, thus explaining the large negative βlg calculated for the transition state geometry that has significantly longer Pα–Onuc distance than the Pα–Olg distance.

show abstract

Section: Resultssupporting

confidence: 89%

Quantum Mechanical Analysis of Nonenzymatic Nucleotidyl Transfer Reactions: Kinetic and Thermodynamic Effects of β–γ Bridging Groups of dNTP Substrates

2014

View full text Add to dashboard Cite

show abstract

“…The corresponding standard free energy change, ~3 kJ mol -1 , is to be compared with -32.2 kJ mol -1 measured for the free energy released on hydrolysis of ATP to AMP and PP i (ref. 19), indicating that the group transfer potential of the aminoacyl ester bond of aa-tRNA amounts to approximately -29 kJ mol -1 (25 °C). The free energy contained in the ester bond of fMet-tRNA fMet (and of peptidyl-tRNAs) is probably comparable.…”

Section: A Site Trna Destabilization and Translocationmentioning

confidence: 99%

Untitled

2000

View full text Add to dashboard Cite

Upon transpeptidylation, the 3' end of aminoacyl-tRNA (aa-tRNA) in the ribosomal A site enters the A/P hybrid state. We report that transpeptidylation of Phe-tRNA to fMetPhe-tRNA on Escherichia coli ribosomes substantially lowers the kinetic stability of the ribosome-tRNA complex and decreases the affinity by 18.9 kJ mol(-1). At the same time, the free energy of activation of elongation factor G dependent translocation decreases by 12.5 kJ mol(-1), indicating that part of the free energy of transpeptidylation is used to drive translocation kinetically. Thus, the formation of the A/P hybrid state constitutes an important element of the translocation mechanism.

show abstract

“…(1)] proceeds extremely slowly in aqueous solution at ambient temperature. Fortunately, it is also strongly endothermic 56, 57 so that the kinetic parameters can be determined by combining the experimental Δ G 0 with the experimental rates for the reverse reaction 58, 59. The analysis of Fersht 58 indicated that the rate constant k 2 [M −1 s −1 ] for the nucleophilic attack of R″O − on amide (when the base B is a water molecule) increases with the decreasing basicity of the amine moiety according to the relationship log k 2 =7.2−0.67 p K a (R′NH 2 ).…”

Section: Resultsmentioning

confidence: 99%

Ab initio/LD studies of chemical reactions in solution: Reference free-energy surfaces for acylation reactions occurring in serine and cysteine proteases

Štrajbl

Florián

Warshel

2000

Int. J. Quant. Chem.

View full text Add to dashboard Cite

ABSTRACT:A systematic ab initio study of the reactions of amides with alcohols and thiols in aqueous solution is presented. This study is aimed at providing well-defined reference free-energy surfaces for the corresponding studies of the catalytic power of serine and cysteine protease. The applied methodology consists of the combined ab initio and Langevine dipoles (LD) solvent model, and a systematic calibration using the available experiments. The study of the base-catalyzed and general-base-catalyzed methanolysis of formamide, which serves as a reference reaction of serine protease, indicates that when a water molecule is the base the initial proton transfer is concerted with the RO − nucleophilic attack. However, with histidine as a general base this reaction is a stepwise process with a shallow surface that can allow also for a concerted path. It is also found that the protonation of the nitrogen of the oxyanion leads to breaking of the CN bond. The study of a reference reaction of cysteine protease indicates that the initial proton transfer to the general base occurs before the RS − attack on the amide. The nucleophilic attack may be concerted with the protonation of the amide nitrogen, but a stepwise process where the protonation occurs after the formation of the tetrahedral intermediate is also possible. The CN bond cleavage appears to be the last step of the reaction. The common belief that thiols have greater tendency to add to carbonyl groups than alcohols is revisited. It is found that this is probably true because the reactivity of thiols can involve unassisted proton transfer to the nitrogen or oxygen of the amide concerted with the nucleophilic attack. The possibility that thiolysis of amides in solution circumvents the general-base catalysis mechanism should thus be taken into account in comparing enzymatic reactions to uncatalyzed solution reactions. Having relatively reliable potential * Permanent address: Institute of Physics, Charles University, Prague, Czech Republic. In addition, our results will be useful for ab initio studies that use the EVB surfaces as reference potentials. Furthermore, any attempts to study these enzymatic reactions by quantum mechanical approaches should be validated by examining the corresponding solution reactions and the present study should be helpful in such validation studies.

show abstract

The Free Energies of Hydrlysis of Some Esters and Thiol Esters of Acetic Acid

Cited by 55 publications

References 0 publications

Quantum Mechanical Analysis of Nonenzymatic Nucleotidyl Transfer Reactions: Kinetic and Thermodynamic Effects of β–γ Bridging Groups of dNTP Substrates

Quantum Mechanical Analysis of Nonenzymatic Nucleotidyl Transfer Reactions: Kinetic and Thermodynamic Effects of β–γ Bridging Groups of dNTP Substrates

Untitled

Ab initio/LD studies of chemical reactions in solution: Reference free-energy surfaces for acylation reactions occurring in serine and cysteine proteases

Contact Info

Product

Resources

About