Abstract
Several compounds with the known ability to perform as inhibitors of advanced glycation endproducts (AGE) have been studied with Density Functional Theory (DFT) through the use of a number of density functionals whose accuracy has been tested across a broad spectrum of databases in Chemistry and Physics. The chemical reactivity descriptors for these systems have been calculated through Conceptual DFT in an attempt to relate their intrinsic chemical reactivity with the ability to inhibit the action of glycating carbonyl compounds on amino acids and proteins. This knowledge could be useful in the design and development of new drugs which can be potential medicines for diabetes and Alzheimer’s disease.
Highlights
It is well established that advanced glycation endproducts (AGEs) are the final products of a series of chemical reactions initiated by the attachment of reducing sugars to free amino groups in proteins, lipids, and nucleic acids [1,2]
The HOMO and LUMO orbital energies, ionization potentials I, electron affinities A, and global electronegativity χ, total hardness η, global electrophilicity ω, electrodonating power, (ω−), electroaccepting power (ω+), and net electrophilicity ∆ω± of the AGE inhibitors calculated with the eight density functionals and the Def2TZVP basis set using water as solvent simulated with the Solvation Model Density (SMD) parametrization of the IEF-PCM model are presented in Tables S1A to S8A of the Electronic Supplementary Materials (ESM)
The latest Minnesota family of density functionals (M11, M11L, MN12L, MN12SX, N12, N12SX, SOGGA11, and SOGGA11X) have been tested for the fulfillment of the KID procedure by comparison of the HOMO- and LUMO-derived values with those obtained through a ∆SCF technique
Summary
It is well established that advanced glycation endproducts (AGEs) are the final products of a series of chemical reactions initiated by the attachment of reducing sugars to free amino groups in proteins, lipids, and nucleic acids [1,2]. Chemical Reactivity Theory or Conceptual Density Functional Theory (DFT) [3,4] provides a series of descriptors that can be useful for the analysis of the molecular properties of known AGE inhibitors, and a starting point for the development of new ones These descriptors are based on the calculation of the energies of the neutral system as well as the corresponding radical cation and anion by means of a ∆SCF technique, that is, the difference in energies between the neutral and the radical ionic species. Notwithstanding, it can be useful for faster calculations of Conceptual DFT descriptors for large molecular systems where the determination of the electronic energy of the radical cation and anion could be computationally costly and difficult to converge
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