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Studies of thiazide compounds in terms of density functional theory
Author(s) -
Latosińska J. N.
Publication year - 2002
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.10404
Subject(s) - chemistry , atomic orbital , density functional theory , delocalized electron , homo/lumo , computational chemistry , localized molecular orbitals , atom (system on chip) , molecular orbital , linear combination of atomic orbitals , atomic physics , basis set , physics , molecule , quantum mechanics , organic chemistry , electron , computer science , embedded system
A systematic study on the impact of hydrogen addition at positions N2 and C3, as well as the role of a substituent at position C3 of the benzothiadiazine ring, on the electronic structure of the chlorothiazide (CTZ) and hydrochlorothiazide (HCTZ) was carried out by the density functional theory (DFT) method. The results have shown the lowering of total energies with the addition of hydrogen atoms at positions N2 and C3. The HOMO and LUMO orbitals were located similarly in the unsaturated ring, along the C9C10 double bond with a delocalization on C5, on the C7C8 double bond, and on the nitrogen atoms N2 (only in CTZ analogs) and N4, regardless of the functional group at C3. The greatest contribution to HOMO in all thiazides comes from the atomic orbitals p z of nitrogen atoms N4; moreover, in the case of HCTZ analogs, in contrast to CTZ ones, the contribution of N2 nitrogen atom orbitals to HOMO is zero. For BTZ, there is a degeneracy in the HOMO orbitals, i.e., there are two orbitals with almost the same energy, one at C9C10 and the other at C7C8, opening the two reactive paths at HOMO and HOMO‐1. The greatest contributions to the LUMO orbitals comes from the atomic orbitals p z of the carbon atom C6 and only the LUMO orbital in BTZ is mostly localized on the carbon atoms C7 and C10. A comparison of the effective charge proves that the positions N2 and N4 can easily accept protons and of them N2 is more favored for HCTZ and CTZ whereas N4 is for the remaining thiazides. The higher charge density and electrostatic potentials are located in the NCN zone, especially on the N4 nitrogen atom. According to increasing electron–donor properties, the substituents can be ordered as CHCl 2 < CH 2 SCH 2 CHCH 2 < CH 2 SCH 2 Ph. Of key importance for stabilization of CTZ‐type compounds is the interaction of the free electron pair localized on N4 with antibonding π orbitals of the double bonds ( n N4 π * N4C3and n N4 π * C9C10 ). The HCTZ type compounds are also stabilized by the interaction of a free electron pair localized on N4 with the antibonding π orbital of the double bond ( n N4 π * C9C10 ) and by that of the bonding π with the antibonding π* orbitals (π C7C8 π * C9C10 ). A complementary objective was to gain some insight into the relationship between the physical and chemical properties and biologic activity of thiazides. The results of DFT calculations were confronted with experimental data from different spectroscopic and physical and chemical studies. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2003