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Structural and electronic effects of the C2’ substituent in 1,4–benzodiazepines
Lígia Rebelo Gomes (1)
, Luís Manuel Neves Belchior Faia Santos (2) , José Beleza (3) , John Nicolson Low (4,*) (1) CIAGEB-Faculdade de Ciências de Saúde, Escola Superior de Saúde da UFP, Universidade Fernando Pessoa, Porto, P-4200-150, Portugal
(2) Centro de Investigação em Química, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Porto, P-4169-007, Portugal
(3) CIAGEB-Faculdade de Ciências de Saúde, Escola Superior de Saúde da UFP, Universidade Fernando Pessoa, Porto, P-4200-150, Portugal
(4) Department of Chemistry, University of Aberdeen, AB24 3UE, Scotland
(*) Corresponding Author
Received: 17 Nov 2010 | Revised: 25 Jan 2011 | Accepted: 11 Jan 2011 | Published: 28 Mar 2011 | Issue Date: March 2011
Abstract
Benzodiazepines are drugs used for treatment of several central nervous system disorders, such as anxiety and sleep. In spite of their wide and popular usage in clinics, the mechanism explaining why a certain pharmacological activity is superimposed onto another for a given benzodiazepine remains unclear. The knowledge of the conformation of benzodiazepines and their electronic charge distribution at molecular surfaces may give new insights into the pharmaco-benzodiazepine receptor interactions, contributing to the improvement of the existing models. In the present study, the solid state geometric and conformational parameters of the available X-ray benzodiazepine structures were analyzed and reviewed. The electronic features of two groups of benzodiazepines with different substituents at C7 and C2’ positions were studied by DFT quantum chemical calculations. The conformations of the molecules with optimized geometry were also analyzed. The relative charge distribution around the benzodiazepinic rings and electrostatic potential mapped on electronic density surfaces were obtained. The ring geometric parameters for the diazepine moiety in 1,4-benzodiazepines, do not vary significantly except for a few compounds in which steric and/or intermolecular interactions play a part. The benzodiazepine ring assumes a pseudo-symmetrical boat conformation and the torsion angle around the C5-Ph bond varies depending on the nature of the substituent on C2’. Also, the presence of the nitro or chloride substituent on the C7 position and the presence of a fluorine atom on the C2’ position significantly alter the relative charge distributions at the attached carbon atoms and the topology of the surface electrostatic potential.
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DOI: 10.5155/eurjchem.2.1.1-7.322
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Thanks are due to Fundação para o Ensino e Cultura Fernando Pessoa for financial support.
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DOI Link: https://doi.org/10.5155/eurjchem.2.1.1-7.322
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European Journal of Chemistry 2011, 2(1), 1-7 | doi: https://doi.org/10.5155/eurjchem.2.1.1-7.322 | Get rights and content
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