DFT Based Electrophilicity Index and QSAR study of Phenols as Anti Leukaemia Agent

Abstract

Density Functional reactivity indices based QSAR study of 49 phenol derivatives is presented in this paper. Two different models to describe the anti leukaemia activity of phenols have been made. First QSAR model includes molecular properties like molecular weight (Mw), hardness (η), chemical potential (µ), total energy, and electrophilicity index (ω). Various regression models have been made and regression quality indicates that these descriptors provides valuable information and have significant role in assessment of activity of phenols. Klopman gave first quantum chemical treatment to describe the reactivity of a chemical system in terms of acidic softness E n and basic softness E m at atomic level. In this paper we have derived the partial electrophilicity by the multiplication of global electrophilicity index (given by Parr etal) and the acidic softness En (given by Klopman). This total electrophilicity index has been used as descriptors along with the other atomic properties like highest negative charge (Q min ) etc in second QSAR model. This model also provides good results. The DFT calculations have been performed by using B88-PW91 GGA energy functional with the DZVP basis set on Cache pro software and the regression models have been made on project leader software associated with CAChe. These DFT models have high predictive power and have sufficient reliability to describe the Anti leukaemia activity of phenols which is clear from its correlation coefficient r 2 and cross validation coefficient r cv 2 .

QSAR-Assisted Virtual Screening of Lead-Like Molecules from Marine and Microbial Natural Sources for Antitumor and Antibiotic Drug Discovery

“…Theoretical studies of the electronic properties and chemical reactivity of quercetin [23], catechin and epicatechin [24] were as well reported. In other studies, the electrophilicity index was related to the ability of the NPs isoprekinamycin, kinamycins and lomaiviticin A acting as antitumor and antibacterial agents [25], to study the antileukaemic activity of phenol [26], and in suppression of breast cancer by chemical modulation of vulnerable zinc fingers in estrogen receptors [27]. Quantum-chemical descriptors have also been used in the analysis of the relations between the structural properties and the antitumoral activity of synthetic chalcones [28].…”

Molecular Geometry, Homo-Lumo Analysis and Mulliken Charge Distribution of 2,6-Dichloro-4-Fluoro Phenol Using DFT and HF Method

“…The energy values of LUMO and HOMO and their energy gap govern a molecule's kinetic stability, chemical responses, spontaneous polarizability, and chemical hardness-softness. [17][18][19].…”

“…The high values of the energy gap indicate the ruggedness, whereas the small value displays the tenderness of the molecular structure. Since they require a significant amount of energy to excite, in comparison to soft molecules, hard molecules are not significantly polarizable [18][19][20]. A molecule is chemically reactive if it has a minimal or nonexistent HOMO-LUMO gap.…”

“…The HOMO-LUMO gap illustrates the molecular fragility of the compound [20][21]. Additional quantity that is estimated is the electrophilicity index, which quantifies the energy loss experienced by a ligand as a result of the maximum electron flow between the donor and acceptor [17][18].…”