CHIH-DFT determination of the molecular structure infrared spectra, UV spectra and chemical reactivity of three antitubercular compounds: Rifampicin, Isoniazid and Pyrazinamide

Abstract

Three of the most frequent antitubercular agents employed against Mycobacterium tuberculosis are: Rifampicin, Isoniazid and Pyrazinamide. It has been proven that the use of these antitubercular agents together, shortens the treatment period from 12-18 months to 6 months [1]. In this work we use a new Density Functional Theory chemistry model called CHIH-DFT (Chihuahua-Heterocycles-Density Functional Theory) that reflects the mixture of Hartree Fock exchange and DFT exchange, according to a mixing parameter based on empirical rules suited for heterocyclic systems. This new chemistry model was used to calculate the molecular structure of these antitubercular compounds, as well as their infrared, UV spectra, chemical reactivity and electronic properties. The UV and infrared spectra were obtained by experimental techniques. The calculated molecular structure, UV and IR spectra values from CHIH-DFT were compared with experimentally obtained values and theoretical studies. These results are in good agreement with experimental and theoretical studies. We also predicted using the relative electrophilicity and relative nucleophilicity concepts as defined by Roy et al. [2] the chemical active sites for the three antitubercular compounds as well as their electronegativity, ionization potential, electron affinity, hardness, dipole moment, E(HOMO)-E(LUMO) gap energy, etc.

Multidimensional infrared spectroscopy reveals the vibrational and solvation dynamics of isoniazid

“…Isonicotinic acid hydrazide (INH), more commonly known as Isoniazid, was first used to treat Mycobacterium tuberculosis, the cause of tuberculosis, over sixty years ago and remains one of the front line therapeutics employed to fight the disease. 1,2 The mode of action of INH is to inhibit the single active site found within InhA, the 2-trans-enoyl-acyl carrier protein reductase enzyme that forms an essential part of the mycolic acid biosynthesis system within M. tuberculosis bacteria. 3,4 INH, the structure of which is shown in Fig.…”

“…Several studies of the molecule have been reported using linear spectroscopy and theoretical modelling to assign the IR spectrum but these are almost universally in the solid phase or matrix-isolated samples. 2,23,24,25 No assignment has been reported under the solution phase, deuterated conditions necessary for biomolecular 2D-IR spectroscopy. In addition, questions have arisen as to the structure of INH.…”

Low Temperature Infrared Spectroscopy Study of Pyrazinamide: From the Isolated Monomer to the Stable Low Temperature Crystalline Phase

“…For example, infrared or Raman data for the compound have been discussed in several of those studies 3,6,8,10,11,[28][29][30] without specification of which polymorph was under investigation. In a recent study, Castro et al 31 reported the infrared spectra of the different polymorphs of PZA, thus filling an important gap on the available knowledge about this compound.…”

Rifampicin adsorbed onto magnetite nanoparticle: SERS study and insight on the molecular arrangement and light effect

“…Contributions of the CH stretching and CH 3 groups from the aliphatic ansa ‐bridge can also be observed in the 2850–2950 cm −1 region [Fig. (a)], whereas the N–CH 3 vibrational mode can be found at 2883 cm −1 . Additionally, the skeletal deformation modes as well as the ring stretching modes of the naphthohydroquinone chromophore can be observed in the 400–1300 cm −1 and 1300−1600 cm −1 regions, respectively.…”