Nucleophilic and general acid catalysis at physiological pH by a designed miniature esteraseElectronic supplementary information (ESI) available: NOESY and TOCSY spectra; Table with NMR assignments and observed NOEs; complete set of kinetic data for Art-Est catalysis; mass spectrum of fumaryl-Art-Est intermediate; rate constants for the spontaneous and catalysed ester hydrolysis. See http://www.rsc.org/suppdata/ob/b4/b404730c/. Coordinates for the structure of Art-Est have been deposited in the Brookhaven Protein Data Bank, code 1v1d.

2004 ◽  
Vol 2 (15) ◽  
pp. 2175 ◽  
Author(s):  
Andrew J. Nicoll ◽  
Rudolf K. Allemann
Keyword(s):  
Mass Spectrum ◽  
Rate Constants ◽  
Kinetic Data ◽  
Acid Catalysis ◽  
Nmr Assignments ◽  
Data Bank ◽  
Supplementary Information ◽  
Protein Data Bank Code ◽  
Complete Set ◽  
Intermediate Rate

Effect of Medium on Reactivity for Alkaline Hydrolysis of p-Nitrophenyl Acetate and S-p-Nitrophenyl Thioacetate in DMSO-H2O Mixtures of Varying Compositions: Ground State and Transition State Contributions

2021 ◽  
Author(s):  
Ik-Hwan Um ◽  
Seungjae Kim
Keyword(s):  
Transition State ◽  
Alkaline Hydrolysis ◽  
Ground State ◽  
Rate Constants ◽  
Kinetic Data ◽  
Reaction Medium ◽  
Stepwise Mechanism ◽  
Rate Determining Step ◽  
Leaving Group ◽  
Hydrolysis Of

Second-order rate constants (kN) for reactions of p-nitrophenyl acetate (1) and S-p-nitrophenyl thioacetate (2) with OH‒ have been measured spectrophotometrically in DMSO-H2O mixtures of varying compositions at 25.0 ± 0.1 oC. The kN value increases from 11.6 to 32,800 M‒1s‒1 for the reactions of 1 and from 5.90 to 190,000 M‒1s‒1 for those of 2 as the reaction medium changes from H2O to 80 mol % DMSO, indicating that the effect of medium on reactivity is more remarkable for the reactions of 2 than for those of 1. Although 2 possesses a better leaving group than 1, the former is less reactive than the latter by a factor of 2 in H2O. This implies that expulsion of the leaving group is not advanced in the rate-determining transition state (TS), i.e., the reactions of 1 and 2 with OH‒ proceed through a stepwise mechanism, in which expulsion of the leaving group from the addition intermediate occurs after the rate-determining step (RDS). Addition of DMSO to H2O would destabilize OH‒ through electronic repulsion between the anion and the negative-dipole end in DMSO. However, destabilization of OH‒ in the ground state (GS) is not solely responsible for the remarkably enhanced reactivity upon addition of DMSO to the medium. The effect of medium on reactivity has been dissected into the GS and TS contributions through combination of the kinetic data with the transfer enthalpies (ΔΔHtr) from H2O to DMSO-H2O mixtures for OH‒ ion.

scholarly journals Reactivity of cyclohex-1-enylcarboxylic and 2-methylcyclohex-1-enylcarboxylic acids with diazodiphenylmethane in aprotic solvents

2000 ◽  
Vol 65 (12) ◽  
pp. 839-846
Author(s):  
Jasmina Nikolic ◽  
Gordana Uscumlic ◽  
Vera Krstic
Keyword(s):  
Hydrogen Bond ◽  
Rate Constants ◽  
Kinetic Data ◽  
Linear Regression Analysis ◽  
Spectroscopic Method ◽  
Reaction Rates ◽  
Aprotic Solvents ◽  
Experimental Conditions ◽  
Hydrogen Bond Acceptor ◽  
Protic Solvents

Rate constants for the reaction of diazodiphenylmethane with cyclohex-1-enylcarboxylic acid and 2-methylcyclohex-1-enylcarboxylic acid were determined in nine aprotic solvents, as well as in seven protic solvents, at 30?C using the appropriate UV-spectroscopic method. In protic solvents the unsubsituted acid displayed higher reaction rates than the methyl-substituted one. The results in aprotic solvents showed quite the opposite, and the reaction rates were considerably lower. In order to explain the obtained results through solvent effects, reaction rate constants (k) of the examined acids were correlated using the total solvatochromic equation of the form: log k=logk0+s?*+a?+b?, where ?* is the measure of the solvent polarity, a represents the scale of the solvent hydrogen bond donor acidities (HBD) and b represents the scale of the solvent hydrogen bond acceptor basicities (HBA). The correlation of the kinetic data were carried out by means of multiple linear regression analysis and the opposite effects of aprotic solvents, as well as the difference in the influence of protic and aprotic solvents on the reaction of the two examined acids with DDM were discussed. The results presented in this paper for cyclohex-1-enylcarboxylic and 2-methylcyclohex-1-enylcarboxylic acids were compared with the kinetic data for benzoic acid obtained in the same chemical reaction, under the same experimental conditions.

scholarly journals A Molecular Docking of New 9β-Halogenated Prostaglandin Analogues

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 21
Author(s):  
Constantin I. Tanase ◽  
Lucia Pintilie ◽  
Elena Mihai
Keyword(s):  
Molecular Docking ◽  
Acid Catalysis ◽  
Data Bank ◽  
Docking Study ◽  
Ester Group ◽  
Prostaglandin Analogue ◽  
Molecular Docking Study ◽  
Prostaglandin Analogues ◽  
Cytoprotective Activity ◽  
Long Time

Prostaglandins (PGs) with cytoprotective activity were studied for a long time, and a few PGE1 and PGE2 stable analogues were promoted as drugs: arbaprostil, enprostil, misoprostol, and rioptostol. Similarly, nocloprost, a 9β-chlorine prostaglandin analogue, and many 9β- and 11β-substituted prostaglandins were synthesized and studied for their biological activity. We previously synthesized new 9β-halogenated prostaglandins with an ester group at the carbon atom 6 (PGs numbering) by the reaction of a δ-lactone intermediate with diols in acid catalysis. These compounds were used in the current molecular docking study to determine their potential cytoprotective (anti-ulcer) activity. The current study was done with the CLC Drug Discovery Workbench 2.4. software and an oxidoreductase enzyme receptor, chosen from the Protein Data Bank, ID: 4KEW (www.rcsb.org). We used two recognized drugs, omeprazole (co-crystallized with the enzyme) and nocloprost, as the standard. The 9β-halogenated prostaglandin analogs were docked. Nocloprost and all 9β-halogenated compounds had docking scores greater than that of omeprazole. The majority of the 9β-halogenated analogs had docking scores even greater than that of nocloprost, indicating that these compounds could have potential cytoprotective (anti-ulcer) activity. A few correlations between docking score and substituents on the prostaglandin skeleton were found.

scholarly journals SEARCH FOR GLIOMA DIRECT BINDING SITE OF ALKALOID USING PROTEIN-LIGAND ANT SYSTEM®

2018 ◽  
Vol 11 (15) ◽  
pp. 65 ◽  
Author(s):  
Yusnita Rifai
Keyword(s):  
Hydrogen Bond ◽  
Binding Site ◽  
Internal Control ◽  
Data Bank ◽  
Protein Data Bank Code ◽  
Ant System ◽  
Hydrogen Bond Interaction ◽  
Good Score ◽  
Score Result ◽  
Native Ligand

Objective: This research aims to know the best affinity and the best chemical conformation of anticancer compounds from alkaloid groups that have closed direction to Glioma-associated oncogene using protein-ligand ant system (PLANTS®). The interaction energy and hydrogen bond are included as evaluated targets.Methods: In this research, 27 ligands with root mean square deviation score at 1.614 Å and cyclopamine as native ligand are used. Meanwhile, staurosporinone acts as gliomas directed-binding-site-internal-control. Each ligand is docked in GLI with Protein Data Bank code 2GLI using two methods, GLI contains water and without water.Results: PLANTS® score for native ligand in the first and the second method is −73.9002 and −73.2700, respectively. Pancracristine, homoharringtonine, and sanguinarine showed PLANTS® score closed to the cyclopamine score result, but their hydrogen bond interaction differed from native ligan interaction. Evodiamine ligand has a good score and hydrogen bond to the same amino acid of protein GLI, which are GLU 175 and THR 173. This result indicated that evodiamine has the same identical mechanism as staurosporinone.Conclusion: The evodiamine is determined to have the same working mechanism as a GLI inhibitor.

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