Calculation of Substituent Effects on p<i>K</i><sub>a</sub> Values for Pyrone and Dihydropyrone Inhibitors of HIV-1 Protease

Topol, Igor A.; Burt, Stanley K.; Rashin, A. A.; Erickson, John W.

doi:10.1021/jp992691v

Cited by 35 publications

(23 citation statements)

References 53 publications

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“…1 Examples 1-24 include carboxylic acids, [7][8][9]11,14,[17][18][19] alcohols, 11 thiols, 11 phenols, 21 pyrone derivatives, 12 amines, 3 imidazoles, 5,24 hydrated transition metal cations, 2 transition metal complexes, 16 phosphoranes, 22 and DNA (RNA) bases. 6,15,23 Recent applications are extended to the evaluation of pK a values of 1) intermediate species that are not easily measured experimentally, 22 2) weak organic acids with high pK a values, 13 which cannot be measured experimentally in aqueous phase, and 3) molecules having multiple protonation sites.…”

Section: Introductionmentioning

confidence: 99%

Calculation of the Solvation Free Energy of the Proton in Methanol

Hwang¹,

Chung²

2005

Bulletin of the Korean Chemical Society

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The solvation free energy of proton in methanol was calculated by B3LYP flavor of density functional calculations in combination with the Poisson-Boltzmann continuum solvation model. In order to check the adequacy of the computation level, the free energies of clustering in the gas phase were compared with the experimental data. The solvents were taken into account in a hybrid manner, i.e. one to five molecules of methanol were explicitly considered while other solvent molecules were represented with an implicit solvation model.

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Section: Introductionmentioning

confidence: 99%

Calculation of the Solvation Free Energy of the Proton in Methanol

Hwang¹,

Chung²

2005

Bulletin of the Korean Chemical Society

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“…We used ∆Gg 7.76 = -6.28 kcal/mol from the literature. 11,12 All QM calculations used the Jaguar v 5.5 quantum chemistry software. 13 To calculate the geometries and energies of the various molecules, we used the B3LYP flavor of density functional theory (DFT), which includes the generalized gradient approximation and a component of the exact Hartree-Fock (HF) exchange.…”

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confidence: 99%

Study of 7-Methylguanine on pK_aValues by Using Density Functional Theoretical Method

Hwang¹,

Jang²,

Cho³

et al. 2010

Bulletin of the Korean Chemical Society

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Methylation of DNA by endogenous methylating agents generates a variety of genotoxic adducts.1 The N7 position of guanine is known as the most nucleophilic site within the heterocyclic bases of DNA.2 Accordingly, N7-methylguanine (7MeG) is the one of the most prevailing forms of the methylated guanine. 7MeG is also generated by methylation in order to be used as a probe of protein-DNA interactions and DNA sequencing. Recently, a DNA double helical structure of a 25-mer containing a 7MeG was reported, which revealed the base pairing characteristics of 7MeG.1 Information on the acid dissociation constants and the relative populations of various tautomers would provide valuable clues toward optimizing analysis of 7MeG and to understand the biological consequences of the modified base.We have developed a scheme based on density-functional theoretical calculations in combination with the Poisson-Boltzmann continuum solvation model for water to predict pKa values and the major tautomeric forms of a number of nucleobases, their oxidative damage products, 3-5 and heteronuclear aromatic compounds. 6,7 As well as macroscopic pKa values, we reproduced the micro pKa values of individual protonation sites of purine nucleobases.8 Hydrogen transfer between paired nucleobases was also investigated using the same computational model. Among methylated guanine species, we have already reported computations on the tautomerism and pK a values of 9-methylguanine (9MeG) and 7,9-dimethylguanine.8 Gas-phase vibrational experiments and computation results on 1,7-dimethylguanine, 7MeG, and 9MeG were also reported. 10In the current work, we report calculated relative stabilities of the tautomers of 7MeG at each ionization stage and the pKa values of 7MeG in aqueous solution.pKa calculations on the nucleobases and their derivatives are complicated due to the presence of multiple tautomers with different site-specific microscopic pKa values. A way to estimate the overall macroscopic pKa from the site-specific pKa's of the tautomers devised in our previous studies and the details of the computation scheme have been presented elsewhere. 3,4For a deprotonation process leading the i-th tautomer of an acid HA into the j-th tautomer of the conjugate base A -, the Gibbs energy of deprotonation reaction is calculated as (1) and the corresponding micro pKa ij values is given bywhere R is the gas constant and T is 298.15 K. From this micro pK a ij value, the partial population of the i-th tautomer out of all of the acid species ( fi), and the partial population of the j-th tautomer out of all of the conjugate base species ( fj ' ), the macro pKa value is estimated as 4 pKa = pKa ij -log fi + log fj ' .The standard free energy of each species (HA, A -, and H + ) in water, ∆Ga 0 q, can be written as the sum of the gas-phase standard Gibbs energy ∆Gg 0 and the standard Gibbs energy of solvation in water ∆Gs 0 olv:The standard Gibbs energy of each species in the gas phase, ∆Gg 0 , is obtained byThe total energy of the molecule at 0 K (E0 K) is calculated ...

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“…This understanding can be essential for interpretation of experimental values in various systems (Topol et al, 2000;Ho, Coote, 2010).…”

Section: Introductionmentioning

confidence: 98%

Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution

Kiani

Abbaszadeh

Pousti

et al. 2015

Braz. J. Pharm. Sci.

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In the present work, acid dissociation constant (pK a ) values of muscimol derivatives were calculated using the Density Functional Theory (DFT) method. In this regard, free energy values of neutral, protonated and deprotonated species of muscimol were calculated in water at the B3LYP/6-31G(d) basis sets. The hydrogen bond formation of all species had been analyzed using the Tomasi's method. It was revealed that the theoretically calculated pK a values were in a good agreement with the existing experimental pK a values, which were determined from capillary electrophoresis, potentiometric titration and UV-visible spectrophotometric measurements.Uniterms: Nanodrug. Muscimol. Acid/dissociation constants. Computational chemistry. Density Functional Theory.No presente trabalho, calculou-se a constante de dissociação do ácido (pK a ) dos derivados de muscimol, utilizando-se o método da teoria do funcional de densidade (DFT). Com esse objetivo, calcularam-se os valores das espécies neutra, protonada e desprotonada do muscimol em água em base B3LYP/6-31G(d). A formação da ligação de hidrogênio de todas as espécies foi analisada utilizando o método de Tomasi. Demonstrou-se que os valores de pKa calculados teoricamente estavam em boa concordância com os valores experimentais disponíveis, determinados por eletroforese capilar, titulação potenciométrica e medidas por espectrofotometria UV-visível.Unitermos: Nanofármaco. Muscimol. Ácido/constantes de dissociação. Química computacional. Teoria do funcional de densidade.

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Calculation of Substituent Effects on pK_a Values for Pyrone and Dihydropyrone Inhibitors of HIV-1 Protease

Cited by 35 publications

References 53 publications

Calculation of the Solvation Free Energy of the Proton in Methanol

Calculation of the Solvation Free Energy of the Proton in Methanol

Study of 7-Methylguanine on pK_aValues by Using Density Functional Theoretical Method

Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution

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Calculation of Substituent Effects on pKa Values for Pyrone and Dihydropyrone Inhibitors of HIV-1 Protease

Cited by 35 publications

References 53 publications

Calculation of the Solvation Free Energy of the Proton in Methanol

Calculation of the Solvation Free Energy of the Proton in Methanol

Study of 7-Methylguanine on pKaValues by Using Density Functional Theoretical Method

Theoretically nanoscale study on ionization of muscimol nano drug in aqueous solution

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Calculation of Substituent Effects on pK_a Values for Pyrone and Dihydropyrone Inhibitors of HIV-1 Protease

Study of 7-Methylguanine on pK_aValues by Using Density Functional Theoretical Method