A correlation between the energies of electronic singlet transitions in benzodiazepines and their biological activity, which was revealed earlier by means of negative ion mass spectrometry with resonance electron capture, has been verified with a UV absorption spectroscopy investigation. Also, it has been noted that the energies of electronic singlet transitions in benzodiazepines are close in value to the ionization energies of atoms Cs, Rb, K, Na, Li and Tl, the cations of which are known to play an important role in nerve cell excitation processes. Copyright 1999 John Wiley & Sons, Ltd.

In order to find which of the electron structure features of benzodiazepine molecules control their biological activity, a series of benzodiazepine derivatives was investigated by means of negative ion mass spectrometry with resonance electron capture. The resonance curves for negative ion effective yields are presented. Comparison within a series demonstrates a significant (0.6–1.5 eV) shift of curve maxima towards high electron energies (destabilization) for inactive compounds. It is concluded that the destabilization of resonances reflects an increase in energy of several first electronic transitions in the neutral benzodiazepine molecules, and is related to the second (inactive) conformer, the pseudo‐chair. It is suggested that the energies of the electronic transitions are the sought feature of the electron structure of a benzodiazepine molecule which correlates with its activity, and that the stereospecific structure of the benzodiazepine conformers affect the activity via this feature. Copyright © 1998 John Wiley & Sons, Ltd.

In order to find which of the electron structure features of benzodiazepine molecules control their biological activity, a series of benzodiazepine derivatives was investigated by means of negative ion mass spectrometry with resonance electron capture. The resonance curves for negative ion effective yields are presented. Comparison within a series demonstrates a significant (0.6-1.5 eV) shift of curve maxima towards high electron energies (destabilization) for inactive compounds. It is concluded that the destabilization of resonances reflects an increase in energy of several first electronic transitions in the neutral benzodiazepine molecules, and is related to the second (inactive) conformer, the pseudo-chair. It is suggested that the energies of the electronic transitions are the sought feature of the electron structure of a benzodiazepine molecule which correlates with its activity, and that the stereospecific structure of the benzodiazepine conformers affect the activity via this feature. # 1998 John Wiley & Sons, Ltd. Received 1 August 1998; Revised 30 September 1998; Accepted 3 October 1998 Benzodiazepines (BD) have aroused considerable interest in the field of pharmacology because of well-known biological activity properties of a number of their representatives. BD analogues are widely used in pharmacological practice as tranquilizers due to their psychotropic effect.1 Recently, investigations have expanded the field of BD uses through production of new compounds with properties such as antiarrhythmic effect 2 and anti-HIV activity. 3,4 It is not surprising that, for a number of years, BDs have represented classical objects for physicochemical studies, particularly in the area of structure-activity relationships. Our own previous investigations of BDs were performed by means of negative ion mass spectrometry (NIMS) with resonance electron capture. 5,6 It was found that in the gas phase, a BD molecule has two nonequivalent conformers of the sevenmembered heterocycle, which are in dynamic equilibrium. One of these is a pseudo-boat (C 1 ) that is well-known from X-ray data, 7 and features a cis configuration of NH and CO groups. The other conformer is a pseudo-chair (C 2 ) with a trans configuration of these groups.In contrast to the C 1 conformer, the C 2 conformer does not exhibit any activity and so the net value of BD activity (usually measured via the degree of antagonism to corazol) is controlled by a quantitative relationship between the C 1 and C 2 conformers of a particular BD molecule. This result was obtained on the basis of a correlation found between the activity values and certain NI mass spectra characteristics within a BD series. Later, the conclusions described in previous works 5,6 were confirmed by the results of investigations carried out by means of infrared spectroscopy, which revealed the existence of a correlation between the activity values and the ability of BD molecules to form cyclic dimers through the NH and CO groups. 8 It was found that BD molecules with lower activity values...