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 (ΔE_synthon, 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 ΔE_{acid-pyridine} and ΔE_acid-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 ΔE_synthon 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.