Electronic and physicochemical properties of selected nitrofurans: A theoretical study

Abstract

ABSTRACT:A relationship between the chemical structure and antibacterial activity of nitrofurans is not still completely elucidated; however, from a therapeutics point of view it has been observed that the position of the nitro group is a relevant feature for them to show antibacterial activity. In this work, we performed an ab initio study of some selected nitrofurans at the Hartree-Fock, second-order Møller-Plesset, and Density Functional levels of theory with the purpose of obtaining several electronic structural and physicochemical properties of nitrofurans. The relative acidity of the azomethine group of nitrofurans was analyzed through the deprotonation energy. The results reveal that the less acidic molecules possess antibacterial activity. The bond order analysis suggests that the activity of the nitrofurans could be affected by the electroattracting properties of the substituent. An atomic charge and electrostatic potential analysis showed that the azomethine group, the nitro group, and the furenic ring are influenced by the substituent electronegativity. Finally, a structural analysis showed that the nitro group is coplanar with respect to the furenic ring. The present study reveals that the analyzed physicochemical and structural properties may be related to the antibacterial activity of these nitrofuran-type compounds.

Electronic structure and physicochemical properties of selected penicillins

“…Table II reports the values of some selected bond orders: N4C7, C7O8, N16C26, N16H17, C25O26, and C25C27 to establish a connection with some of the features above discussed between the substituents effect on the electronic structure and the acidity properties of these molecules. First, we would like to comment on the relative acidity of the amide group in the side‐chain by analyzing the N16H17 bond order and note that a smaller bond order value may be indicative of larger acidity as was commented in previous work 27–29. It may be observed in Table II that the PG, DI, and CA molecules possess the smallest N16H17 bond order values, in agreement with the charges on the N16 and H17 atoms discussed above and we propose that it may be linked to the acidic properties of these molecules.…”

“…Third, to analyze the electron donor/attractor properties of the substituents and the reactivity of the aminoacyl side‐chain with respect to the pharmacophore group, we also study the charges on the O26, N16, and H17 atoms, and note in Table I that the PG, DI, and CA molecules possess the smaller negative values on the N16 atom, and the smaller positive value on the H17 atom, as compared with the rest of the molecules, which might be related to the acidic properties of these molecules, i.e., the PG, DI, and CA molecules seem to be less acidic than the rest. It is worth mentioning that the calculation of proton affinities and protonation energies may provide alternate methods of analyzing the acidity of the aminoacyl group and the strength of the hydrogen atom (H17) as it has been studied in previous work 28, 29. Efforts have been undertaken in this laboratory to support our conjecture about the acidic nature of the H17 atom.…”

“…1). Furthermore, a bond order analysis employing the Löwdin scheme 27 at B3LYP/6‐31+G( d ) level was performed to provide an alternative insight into the relative acidity of the amide group and also for the purpose of exploring the substituent effect provoked by the R group 28, 29. Finally, according to the Koopman's theorem 30, global reactivity descriptors such as the ionization potential (I), hardness (η), and the electrophilicity index (ω) 31–33 were calculated.…”

Characterization of electronic structure and physicochemical properties of antiparasitic nifurtimox analogues: A theoretical study

“…Furthermore, Monasterios et al [14] employed a combined computational study using Molecular and Quantum Mechanics methods, in 5-nitrofurane derivatives, with the aim of finding the structural, electronic, and electrostatic requirements which they need to show antibacterial activity. On the other hand, Soriano-Correa et al [15] performed an ab initio study of some selected nitrofurans of the azomethine type at the Hartree-Fock, second-order Møller-Plesset, and DFT levels of theory with the purpose of obtaining several electronic structural and physicochemical properties of nitrofurans. The relative acidity of the azomethine group of nitrofurans was analyzed through the deprotonation energy and the results revealed that the less acidic molecules possess antibacterial activity.…”