Molecular complexes of homologous alkanedicarboxylic acids with isonicotinamide: x-ray crystal structures, hydrogen bond synthons, and melting point alternation

Crystallization of α,ω-alkanedicarboxylic acids (HOOC-(CH2)n-2-COOH, n = 2-6) with isonicotinamide (IN) is carried out in 1:2 and 1:1 stoichiometry. Five cocrystals of (diacid)·(IN)2 composition (diacid = oxalic acid, malonic acid, succinic acid, glutaric acid, and adipic acid) are characterized by X-ray diffraction at 153(2) K. Tapes of acid-pyridine O-H···N and amide-amide N-H···O hydrogen bond synthons stabilize these five crystal structures as predicted by the hierarchic model: the best donor (COOH) and best acceptor group (pyridine N) hydrogen bond as acid-pyridine and the second best donor-acceptor group (CONH2) aggregates as an amide dimer. Glutaric acid and adipic acid cocrystallize in 1:1 stoichiometry also, (diacid)·(IN), with acid-pyridine and acid-amide hydrogen bonds. Synthon energy calculations (ΔEsynthon, RHF/6-31G) explain the observed hydrogen bond preferences in 1:2 (five examples) and 1:1 (two examples) cocrystals. The acid-pyridine hydrogen bond is favored over the acid-amide dimer for strong carboxylic acids because the difference between ΔEacid-pyridine and ΔEacid-amide (-2.21 kcal mol-1) is greater than the difference for weak acids (-0.77 kcal mol-1), which cocrystallize with both of these hydrogen bond synthons. We suggest ΔEsynthon as a semiquantitative parameter to rank hydrogen bond preferences and better understand supramolecular organization in the multifunctional acid-IN system. Melting point alternation in five homologous (diacid)·(IN)2 cocrystals is correlated with changes in crystal density and packing fraction