The Merck Index of Chemicals and Drugs An Encyclopedia for the Chemist, Pharmacist, Physician and Allied Professions Sixth edition Pp xiv + 1167 (Rahway, NJ: Merck and Company, Inc, 1952) 750 dollars; thumb-indexed, 8 dollars

The Merck Index

Linear, zigzag tapes and flat, corrugated sheet structures are described in binary cocrystals 1–9 of some di- and tricarboxylic acids with 4,4′-bipyridine bases and isonicotinamide. Carboxylic acid⋯pyridine O–H⋯N, its proton transfer form N+–H⋯O−, carboxamide dimer N–H⋯O, and extended motifs are present in these crystal structures. Our results show modular expansion of carboxylic acid dimer in neutral cocrystals with pyridine type bases. Even as the structures of these aggregates can be understood from the molecular constituents in a straightforward manner, the nature of acid⋯pyridine synthon, i.e. neutral or ionic, is difficult to anticipate from their ΔpKa values. We modify the ΔpKa
				(pKa conjugate acid of pyridine base – pKa carboxylic acid) rule in COOH–pyridine cocrystals: ΔpKa 3.75 results in proton migration to the ionic interaction N+–H⋯O−. Proton transfer results in the assembly of a supramolecular 3-connected node of cyclohexane tricarboxylate and these anions form chair cyclohexane or parquet grid sheets in 10 and 11. The length of bipyridinium cation plays a role in the overall structure. A novel approach to three-component adducts is crystallization of 1,3cis,5cis-cyclohexane tricarboxylic acid with 4,4′-bipyridine and 4,4′-bipyridine-N-oxide bases of different strengths, which results in a ternary cocrystal 12 sustained via O–H⋯N and O–H⋯O− hydrogen bonds.

Tape and layer structures in cocrystals of some di- and tricarboxylic acids with 4,4′-bipyridines and isonicotinamide. From binary to ternary cocrystals

Interpenetration in extended three-dimensional (3D) arrays has been investigated by a systematic analysis of the crystallographic structural databases, using an ad hoc version of the program package TOPOS. In this paper we describe the comprehensive results of our investigation of interpenetration in organic hydrogen-bonded 3D arrays from the Cambridge Structural Database. The great interest in the self-assembly of organic molecules into hydrogen-bonded supramolecular arrays has prompted us to investigate these systems at a rather unusual level; that is, beyond the formation of synthons, we have examined the topologies of the resulting networks and looked for their entanglements. Within 3D architectures we have extracted a complete list including 122 different motifs showing the phenomenon of interpenetration (76 unseen by the original authors). These organic networks include species assembled by a single or by different building blocks; they are discussed and classified according to the previously introd...

Interpenetrated Three-Dimensional Networks of Hydrogen-Bonded Organic Species: A Systematic Analysis of the Cambridge Structural Database

A cocrystal is only expected to form if it is thermodynamically more stable than the crystals of its components. To test whether this can be predicted with a current computational methodology, we compare the lattice energies of 12 cocrystals of 4-aminobenzoic acid, 8 of succinic acid and 6 of caffeine, with the sums of the lattice energies of their components. These three molecules were chosen for their potential use in pharmaceutical cocrystals and because they had sufficient determinations of cocrystals and corresponding partner crystal structures in the Cambridge Structural Database. The lattice energies were evaluated using anisotropic intermolecular atom−atom potentials, with the electrostatic model and the intramolecular energy penalty for changes in specified torsion angles derived from ab initio calculations on the isolated molecules. The majority of the cocrystals are calculated to be more stable than their components, but the energy difference is only large in a few of the cases where the partne...

Can the Formation of Pharmaceutical Cocrystals Be Computationally Predicted? I. Comparison of Lattice Energies

A family of supramolecular reagents containing two different binding sites, pyridine and amino-pyrimidine, were allowed to react with iodo- or bromo-substituted benzoic acids in order to assemble individual molecules into larger architectures with precise intermolecular interactions, using a combination of hydrogen- and halogen-bonds. The hydrogen-bond based amino-pyrimidine/carboxylic acid or amino-pyrimidinium/carboxylate synthons are responsible for the assembly of the primary structural motif in every case (7/7 times, 100% supramolecular yield), while I···N, Br···N, and I···O, halogen bonds play a structural supporting role by organizing these supermolecules into extended 1D and 2D architectures (5/7 times, 71% supramolecular yield). These results illustrate how two different noncovalent interactions can be employed side-by-side in the reliable construction of extended molecular solid-state networks with predictable connectivity and dimensionality.

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Supramolecular synthesis based on a combination of hydrogen- and halogen bonds.

The asymmetric unit of the title compound, 2C9H8N+·CuCl42−·2H2O, comprises one quinolinium cation, one water mol­ecule and one-half of the CuCl42− anion with the other half generated by crystallographic twofold symmetry. The water mol­ecules are linked to the anions through O—H⋯Cl hydrogen bonds to form two-dimensional molecular networks parallel to (110). The cations are arranged between two networks in parallel stacks. The N—H⋯O, C—H⋯O and C—H⋯Cl intermolecular hydrogen bonds link the cations and the anion networks to form a three-dimensional network.

Bisquinolinium tetra­chloro­cuprate dihydrate

The solid-state packing of sulfur substituted 2-aminopyrimidines and the occurrence of N-H—S hydrogen-bonding associations

The structure of the title compound, C9H11NO2, (I), comprises a flat mol­ecule arranged, head-to-tail, in linear ribbon arrays via a N—H⋯O=C association These ribbons end-on form a herring-bone structure interconnected via N—H⋯N association The structure was first determined in 1987 [Sinha & Pattabhi (1987) Proc Indian Acad Sci Chem Sci 98, 229–234] in the orthorhombic space group P212121, with R = 0120, whereas similar cell dimensions and an increased β angle in the present study resulted in monoclinic space group P21/c, with R = 0065

Monoclinic form of ethyl 4-aminobenzoate (benzocaine)

The hydrogen-bonding networks of 2-amino-4-phenyl-1,3-thiazole derivatives

The structure of the title compound, C9H8N4, comprises non-planar mol­ecules that associate via pyrimidine N—H⋯N dimer R^2_2(8) hydrogen-bonding associations [N⋯N 3.1870 (17) A] and form linear hydrogen-bonded chains via a pyrimidine N—H⋯N(pyridyl) interaction [N⋯N 3.0295 (19) A]. The dihedral angle between the two rings is 24.57 (5)°. The structure of the 1:1 adduct with 4-amino­benzoic acid, C9H8N4·C7H7NO2, exhibits a hydrogen-bond­ing network involving COOH⋯N(pyridyl) [O⋯N 2.6406 (17) A], pyrimidine N—H⋯N [N⋯N 3.0737 (19) and 3.1755 (18) A] and acid N—H⋯O interactions [N⋯O 3.0609 (17) and 2.981 (2) A]. The dihedral angle between the two linked rings of the base is 38.49 (6)° and the carboxyl­ic acid group binds to the stronger base group in contrast to the (less basic) complementary hydrogen-bonding site.

Ian McClenaghan

Papers

Bisquinolinium tetrachlorocuprate dihydrate

The solid-state packing of sulfur substituted 2-aminopyrimidines and the occurrence of N-H—S hydrogen-bonding associations

Monoclinic form of ethyl 4-aminobenzoate (benzocaine)

The hydrogen-bonding networks of 2-amino-4-phenyl-1,3-thiazole derivatives

2-amino-4-(4-pyridyl)pyrimidine and the 1:1 adduct with 4-aminobenzoic acid.

Ian McClenaghan

Papers

Bisquinolinium tetra­chloro­cuprate dihydrate

The solid-state packing of sulfur substituted 2-aminopyrimidines and the occurrence of N-H—S hydrogen-bonding associations

Monoclinic form of ethyl 4-aminobenzoate (benzocaine)

The hydrogen-bonding networks of 2-amino-4-phenyl-1,3-thiazole derivatives

2-amino-4-(4-pyridyl)pyrimidine and the 1:1 adduct with 4-aminobenzoic acid.

Bisquinolinium tetrachlorocuprate dihydrate