Crystal structures of N6-modified-aminoacid nucleobase analogs (III): hybrids adenine-valeric acid, adenine-hexanoic acid and adenine-gabapentine

In this manuscript we report the synthesis and structural characterization of three aminoacid-adenine-derivatives: N-(7H-purin-6-yl)-5-aminovaleric (N6-5AValAde) (1), N-(7H-purin-6-yl)-6-aminohexanoic (N6-6AHexAde) (2), its hydrochloride form of (3) and N-(7H-purin-6-yl)Gabapentine (N6-GabapenAde) (4). In compound (1) with neutral adenine ring and the chain arranged almost in an orthogonal position, the carboxylic groups interacts with the N(7) and N(6)–H(6) of the neighbour molecule forming 1D supramolecular polymers. It also establishes double and strong N(9)-H···N(3) interaction between adenine rings leading to self-assembled dimers. In the layered compound (2), the adenine also forms self-assembled dimers via double N(9)-H···N(3) interactions. However, conversely to (1), the chain is arranged in the same plane of the ring facilitating the formation of coplanar self-assembled dimers via the Hoogsteen face. In the hydrochloride form of N6-6AHexAde (compound 3) the adenine ring is protonated in N(1) which is hydrogen bonded to the chloride anion [N(1)-H···Cl = 2.198A]. As in neutral compound (1), the carboxylic group is bound to N(7) and H-N(6) of a neighbour molecule and the double and strong [N(9)-H···N(3)= 2.069A] interaction between coplanar adenine rings is present. A common feature of compounds (1)–(3) (linear amino-acid), is the formation of adenine···carboxylic group interactions via de Hoogsteen site of adenine and also adenine···adenine self-association via N(9)-H···N(3) interactions. In compound (4), that incorporates the anticonvulsant gabapentine chain attached to the adenine ring, organize its 3D packaging again with protonated carboxylate and N(7)/H-N(6) contacts: [O(19)-H····N(7) and O(18)···HN(6)] and a water molecule that holds 3 different molecules together [O(18)···H1WB, N(3)···H1WA and O(1W)···H-N(9)]. Again stacking interaction between eclipsed pyrimidine rings in anti disposition [C(5)···C(2) / C(2)···C(5) of 3.387A] is observed. Finally, we have studied the noncovalent interactions observed in the solid state architecture by using DFT calculations and rationalized the interactions using Molecular Electrostatic Potential surfaces and the quantum theory of “Atoms-in-Molecules”. The aim of this study is to investigate the competition between homodimer formation by the Hoogsteen face of the adenine/adeninium, self-association of the carboxylic group or through the interaction of the carboxylic group with the adenine/adeninium cation.