Assessing the Efficacy of Nonsteroidal Anti-Inflammatory Drugs Through the Quantum Computation of Molecular Ionization Energies

Abstract

The clinical efficacy of nonsteroidal anti-inflammatory drugs has been related to ionization energies [Mehler and Gerhards, Int. J. Quantum Chem. 1989, 25, 205]. In this paper we employ modern quantum-chemical calculations to re-examine the statistical correlation between clinical efficacy and ionization energies. Ionization energies are computed by density functional theory, with and without Koopman's theorem, for a series of salicylic acids and phenols whose activities, or efficacy, are known. Using a regression analysis, we show that improving the treatment of electron correlation beyond previous studies enhances the statistical correlation between clinical activities and ionization energies.

Valence orbital response to pseudorotation of tetrahydrofuran: A snapshot using dual space analysis

“…39 Table I lists the vertical IPs of the ͑minima͒ C s and C 2 conformers in valence space, respectively, calculated using HF/aug-cc-pVTZ, SAOP/et-pVQZ, and B3LYP/et-pVQZ models. It is seen in this table that the orbital symmetries of the C s and C 2 conformers produced using the three models are consistent for the C s conformer, whereas the order of the 4b and 6a orbital pair ͑highlighted in the table͒ for the C 2 conformer in the HF/aug-cc-pVTZ and SAOP/et-pVQZ models are altered.…”

Koopmans′ Analysis of Chemical Hardness with Spectral‐Like Resolution

“…Among most preeminent approaches in this direction are the electron propagation theory (through considering the self-energy operator) [46];disproving the existence of ionization potential as the lowest eigenvalues of KT but generalizing it to the arbitrarily close value to IP [43]; interpreting the self-consistent Hartree-Fock field as coupled harmonic oscillators evolving in a nonlinear potential [47]; variationally extending KT to restricted open-sells canonical orbitals which nevertheless overestimate the Aufbau principle [48]; differentiating between vertical and adiabatic ionization potentials for the strongest line of the band and for the 0 → 0 band transition, respectively [49]; establishing the connection with DFT through Janak's theorem and proving its reliability for large molecular systems (including fullerenes or boron nitride nanotubes B 48 N 48 ) [50]; including the negative electron affinity extensions within DFT for halogenated small organic molecules [51]; establishing the direct connection of the frontier orbitals with the pi-electrons and of the electronic transfer of conjugated aromatic systems [52];driving the electronic transfer in alfa-substituted organic polymers [53], providing with optical spectra analysis for intervalence complexes formed by organic bridges between radical ions [54]; till the modeling of anti-inflammatory activities of clinical drugs acting through ionization processes in special [55] and by chemical reactivity indices and DFT in general [56–62]. …”

“…till the modeling of anti-inflammatory activities of clinical drugs acting through ionization processes in special [55] and by chemical reactivity indices and DFT in general [56–62]. …”

Comment on “Assessing the Efficacy of Nonsteroidal Anti-Inflammatory Drugs Through the Quantum Computation of Molecular Ionization Energies”

“…Shakman and Mazziotti have calculated the ionization energies (IE) of 12 salicylic acids and 15 phenols and examined the statistical correlations between these IE and the efficacy of these 27 molecules, acting as anti-inflammatory agents. To calculate these IE, the authors employed the Hartree−Fock method and density functional theory (DFT), using the B3LYP and PBEPBE functionals with and without Koopmans’ theorem .…”

“…The correlation coefficients R obtained by Shakman and Mazziotti for the 27 molecules, which they selected, are 0.66 and 0.56 for the Hartree−Fock method and in a range between 0.69 and 0.72 for the density-functional methods. For the same 27 molecules, using a semiempirical AM1 method carried out with the Hyperchem 4 program, we obtain a linear correlation expression: pIC 50 = 2.89 E (HOMO) + 31 n = 27 R = 0.83 The corresponding E (HOMO) and pIC 50 values of eq are reported in a Table S1, available in the Supporting Information.…”