Hydrogen bonds of anti-HIV active aminophenols

Abstract

UDC 539.1.047;543.42 Analysis of IR-Fourier spectra from solutions and crystals of antiviral sulfo-containing aminophenols has shown that various types of intramolecular and intermolecular interactions can occur in molecules of these compounds. Three types of intramolecular hydrogen bonds (O-H⋅⋅⋅N, O-H⋅⋅⋅O=S=O, and N-H⋅⋅⋅O=S=O) are formed in CCl4 solutions of the sulfo-containing aminophenols. The formation of intermolecular H-bonds in- volving the NH- and OH-groups and the preservation of the intramolecular O-H⋅⋅⋅O=S=O H-bond are char- acteristic of the anti-HIV active aminophenol crystals. Spectral attributes are determined in order to distinguish between the anti-HIV active and inactive sulfo-containing aminophenols. Introduction. HIV-infection is an infectious disease that develops in an organism as the result of the multi- year presence in lymphocytes, macrophages, and nerve-cell tissue of human immunodeficiency virus (HIV). It is char- acterized by progressive degeneration of the immune system that leads to the death of the patient from secondary diseases, which are described as acquired immunodeficiency syndrome (AIDS), or subacute encephalitis (1). The incorporation into medical practice of highly active antiretroviral therapy (ART), which is used in con- junction with therapy of opportunistic infections, enabled the understanding of HIV-infection to be reconsidered now as a rapidly progressing fatal disease and to treat it as a chronic disease requiring life supporting therapy (2). It seemed necessary to discover new compounds with high anti-HIV activity that were simple to prepare and promising for development based on them of new drugs. Derivatives of aminophenols (AP) are such compounds. It was found that certain AP derivatives exhibit antiradical (3) and antiherpes (4-8) activity. The recently synthesized AP derivatives were capable of suppressing HIV-infection in cell culture (9). The need to study the structures of AP on the molecular level was due to the ability of many drugs to change their pharmacological effect as a function of their polymorphic transformations (10, 11). Widespread use of AP in pharmacology, in particular HIV-therapy, will be possible after identifying the factors that affect their pharma- cotherapeutic activity and also after studying systematically and in detail the electronic structure and determining the behavior of functional groups interacting among themselves and with the environment. Experimental. We studied N-(2-hydroxy-3,5-di-tert-butyl)-4-methylbenzenesulfonamide (AP I), N-(2-methoxy- 3,5-di-tert-butylphenyl)-4-methylbenzenesulfonamide (AP II), N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-methanesul- fonamide (AP III), N-(2-hydroxy-3,5-di-tert-butylphenyl)-4-benzenesulfonamide (AP IV), N-(2-hydroxy-3,5- di-isopropylphenyl)-4-methylbenzenesulfonamide (AP V), and N-(2-hydroxy-3,5-di-isopropylphenyl)-4-benzenesul- fonamide (AP VI):