Effective atomic charges in the ground state near the amine N in AP I (a) and AP IX (b). 

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... to the N atom and were capable of intra- and intermolecular interactions (IaMI and IeMI) in solutions and molecular crystals [13–19]. As already noted, the biological activity presupposed that the molecules were involved in IeMI. The proton- acceptor ability of the various molecular fragments was determined primarily by the magnitude of the negative effective charge. Positive effective charges of atoms close to this fragment could affect the MEP minimum, which was an integral characteristic that was often linked to a particular molecular fragment. According to quantum-chemical calculations, unsubstituted AP had two MEP minima. The minimum U = − 301 kJ/mol belonged to the hydroxyl O atom (Table 1, compound AP 0); U = –193 kJ/mol, to the amine N atom. Introducing two t -butyl substituents increased the MEP of the OH group to U = –345 kJ/mol (AP 01) and decreased MEP of the amine to U = –145 kJ/mol. MEP calculations showed that a minimum associated with a negative effective charge of the amine N atom was not found for any of the examined AP upon introducing substituents onto the amine. Figure 1 illustrates the reason for its absence. It can be seen that the negative effective charge of the N atom was neutralized (shielded) by either the large positive effective charge of the carbonyl C atom (Fig. 1a) or the even greater positive effective charge of the S atom (Fig. 1b). The butyl group in AP IV and phenyl and methylphenyl fragments in AP VI, AP XI, and AP XII created the greatest MEP associated with the hydroxyl O atom; the methyl in AP II, AP IX, and AP XIII, the lowest (Table 1). It should also be noted that the proton-acceptor ability of the hydroxyl O atom of AP derivatives exhibiting antiviral activity was greater than that of inactive compounds. Let us analyze the electron density distribution on AP fragments and its change caused by the amine substituents, upon which the MEP associated with the hydroxyl O atom depended to a large extent. The calculations indicated that the phenol fragment (Ph 1 ) in the ground state of unsubstituted AP exhibited donor properties; the hydroxyl and amine, acceptor properties (Table 2, compound AP 0). Introducing t -butyl groups into the benzene ring increased the donor properties of the phenol fragment and the acceptor properties of the hydroxyl fragment. The electron-ac- ceptor properties of the amine were practically unchanged (AP 01). Replacing one of the H atoms in the amine by C=OR 1 [where R 1 = CH 3 , CH 2 CH 3 , (CH 2 ) 2 CH 3 , CH 2 Cl, Ph] decreased the donor properties of the phenol ring Ph 1 , practically did not change the effective charge of the hydroxyl, and reduced it on the substituted amine compared with the unsubstituted one. According to the calculations, the donor properties of the phenol fragment and the acceptor properties of the substituted amine were less for any R 1 than for unsubstituted AP (Table 2). Therefore, the negative charge on the hydroxyl in AP molecules with a C=OR 1 group was increased because of the transfer of electron density from both the phenol fragment and the substituted amine. Replacing a H atom of the amine by an SO 2 R 2 fragment (where R 2 = CH 3 , Ph, Ph–CH 3 ) did not qualitatively alter the donor–acceptor properties of the separate fragments of the sulfonyl-substituted AP. However, a phenol fragment Ph 1 with t -butyl (or isopropyl) substituents and also a substituted amine intensified in its presence the donor and acceptor, respectively, capability compared with unsubstituted AP or AP with a C=OR 1 group (Tables 2 and 3). In a quantitative sense, the donor–acceptor properties of fragments of sulfonyl-substituted compounds were related notice- ably to the presence of a phenyl ring in the SO 2 R 2 group. The electron density on the molecular fragments without a phenyl (SO 2 –CH 3 group) of AP IX, AP XIII, and AP XIV was similar to the electron density of fragments of AP derivatives with the C=OR ...