A technique for determining the enantiomeric composition of 2-octanol and α -phenylethylamine with the use of gas chromatography on optically inactive stationary phases is proposed. The technique is based on the formation of symmetrical 1 diastereomeric derivatives upon the interaction of enantiomers with bifunctional achiral reagents: dimethyldichlorosilane, bromochloromethane, and dibromoethane. The reagents were chosen from the viewpoint of the synthesis of diastereomers with a minimum distance between the chiral centers. This minimum distance is responsible for a difference in the energies of interaction of the derivatives with the stationary liquid phase, which is sufficient for the separation of these derivatives.

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The mutual positions of the phenyl fragment and the protonated amino group in the molecules of opiate receptor ligands of various structural classes were studied. It was concluded that two bioactive ligand conformations exist and their implementation does not depend on the structural class of the ligand, selectivity of its action on receptors, or relationship between the agonistic and antagonistic properties. A set of geometric parameters describing the three dimensional arrangement of the phenyl fragment and the protonated amino group in bioactive conformations was proposed; this can be used as a criterion for the geometric assessment of the opiate activity.The interaction of ligand molecules with receptors depends on the structural compatibility of the ligand and the receptor binding site; therefore, the biological activity of the ligands is largely due to their molecular geometry. 1 It is generally accepted that, during interaction, the ligand and the receptor mutually stimulate changes in their spa tial structures that are required for their optimum interac tion. These spatial changes are called the "induced fitting" effect. 2 The ligand conformation in which interactions with the receptor are maximized is called bioactive. The transition from an inactive conformation of the "free" ligand to the bioactive conformation formed in a complex with the receptor is usually accompanied by energy ex penditure, which is equal, on average, to 3-5 kcal mol -1 but may reach tens of kcal per mol if the ligand molecule has a large number of rotational degrees of freedom. If these energy expenditure is made up for by the free energy benefit due to hydrophobic, electrostatic, or other type of ligand-receptor interactions, ligand binding to the re ceptor sites does occur.In the bioactive conformation, the structural fragments of the ligand molecule that interact with the receptor are oriented in a definite manner with respect to each other. The knowledge of the topology of ligand structural frag ments, together with the understanding of the nature of their interaction with the receptor are highly important for elucidation of the reasons for the origin of the ligand affinity for the receptor and the specificity of the ligand action.This study is concerned with the geometric param eters that describe the mutual arrangement of the key structural fragments of molecules of opiate receptor (OR) ligands in their bioactive conformations. These geometric parameters can be used subsequently as a criterion for assessment of the opiate activity in the targeted search for new opiate active compounds, while minimizing expen sive and labor consuming experiments.It was shown in the 1960s that the interaction of nar cotic analgesics with receptors involves the protonated form of the ligand, 3,4 the protonated nitrogen atom, like the phenyl group, being the key structural fragment of OR ligands (see Refs 5-7).It was shown experimentally that the interactions of the protonated N atom and the phenyl group are involved in ligand binding to any typ...

By superposition of the molecules of opiate receptor ligands of various structural classes, three regions responsible for the nonselective ligand affinity were distinguished in the opiate pharmacophore. Spatial arrangement features, electronic properties, the capability of H bond ing and hydrophobic and electrostatic interactions of these regions were determined. The set of geometric parameters found can be used as a criterion for estimation of the opiate activity in simulation of new types of ligands.Key words: opiate receptor ligands, nonselective binding to opiate receptors, a model of the opiate pharmacophore, superposition of molecules.Successful prediction of the "structure-biological ac tivity" relationships should rely on comprehensive infor mation about the pharmacophore, including the set of spatial and electronic features that ensure the supra molecular interactions with the structure of a specific biological target and actuate its biological response. Numerous studies devoted to the structures of opiate pharmacophore (OP) have been carried out. Most often, a set of definite functional groups or typical structural fragments that are distinguished by superposition of opi ate active molecules is proposed as an OP model. The proposed OP models are applicable to either particular structural classes of ligands of opiate receptors (OR) 1-4 or to ligands exhibiting a certain selectivity with respect to OR (see Ref. 5). No general model of OP applicable to all types of OR ligands irrespective of the structural class of the ligand, selectivity of its action on receptors, or the ratio of agonistic/antagonistic properties has been re ported.This study continues the systematic investigation into the structure of OP aimed at the development of a general model of OP not as a set of particular functional groups but a set of some abstractive molecular regions arranged in space in a particular manner and having particular electronic properties. This model will be described by a set of pharmacophore descriptors determining the spatial arrangement of the binding sites of the ligand with the OR, the tendency for H bonding, hydrophobic and electro static interactions, etc.Previously, we have demonstrated that OR ligands can exist as two bioactive conformations (I and II) differ ing in the mutual orientations of the key structural frag ments of OR ligand molecules, namely, the protonated amino group and the phenyl ring. 6 These structural frag ments are responsible for the ligand affinity for OR (elec trostatic interaction of the protonated nitrogen atom with the anionic group of the complementary OR region supplemented by hydrogen bonding 7-10 and π-π inter action of the phenyl fragment with a particular comple mentary section of OR as the electron density donor 11 ). The existence of conformations of I and II does not de pend on the structural class of the ligand, the selectivity of its action on receptors, or the ratio of agonistic/antago nistic properties. Each conformation is described by its own set of geometric param...

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