Two-component Molecular Crystals Research Articles

Design of two-component molecular crystals with defined melting points

The approach proposed in this study disclosed opportunities to predict whether it is possible to obtain co-crystals/salts with melting temperatures above/below the melting temperatures of the individual components.

Prediction of solubility of two-component molecular crystals

An approach which allows one to estimate the solubility of two-component molecular crystals in various solvents at different temperatures without any information on their melting temperatures and enthalpies was proposed.

Two-Component Molecular Crystals: What Is the Difference between Drug–Drug, Drug–GRAS, and CF–CF Databases? Evaluation of Melting Points and Ideal Solubility of Unknown Co-crystals

Two-Component Molecular Crystals: What Is the Difference between Drug–Drug, Drug–GRAS, and CF–CF Databases? Evaluation of Melting Points and Ideal Solubility of Unknown Co-crystals

A combined experimental and theoretical study of miconazole salts and cocrystals: crystal structures, DFT computations, formation thermodynamics and solubility improvement.

Experimental and theoretical screening of multi-component crystal forms of miconazole (MCL), an antifungal drug, with ten aliphatic dicarboxylic acids was performed. Seven multi-component molecular crystals were isolated and identified by different analytical techniques, including the powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TG), and solubility methods. The crystal structures of the MCL hemihydrate, two cocrystals with succinic ([MCL + SucAc] (2 : 1)) and fumaric acids ([MCL + FumAc] (2 : 1)) and one salt with maleic acid ([MCL + MleAc] (1 : 1)) were redetermined. The new cocrystal of MCL with adipic acid ([MCL + AdpAc] (2 : 1)) was investigated by single crystal X-ray diffractometry. It was found that the AdpAc molecule in the cocrystal has an unusual anticlinal conformation. The combination of periodic density functional theory (DFT) computations and quantum topology analysis confirmed the structure-directing role of the acid-imidazole heterosynthon for the considered crystals. The melting temperatures of all the studied multi-component crystals are between the values of the corresponding individual components except [MCL + MleAc] (1 : 1). A thermal analysis has shown that the thermodynamic and thermophysical characteristics of the considered two-component molecular crystals are strongly dependent both on specific interactions (presence of sites of donor-acceptor interactions and hydrogen bond formation) and on nonspecific interactions - molecule polarizability. Based on the sublimation thermodynamics database of molecular crystals, the standard sublimation thermodynamic functions of MCL were evaluated. The thermodynamic functions of multi-component crystal formation based on MCL were calculated and analyzed. Solubility experiments on the MCL multi-component crystals were carried out in isotonic aqueous buffer solutions at pH 1.2 and 6.8 and compared with the solubility of the MCL free base and its nitrate salt. It was found that the salt/cocrystal formation of MCL with dicarboxylic acids considerably increased the MCL solubility in pH 6.8 buffer. The biggest MCL solubility enhancement was observed in the [MCL + TartAc] (1 : 1) salt. The solubility value of MCL in the [MCL + TartAc] (1 : 1) salt is commensurate with the commercial MCL nitrate salt.

Formation Thermodynamics of Two-Component Molecular Crystals: Polymorphism, Stoichiometry, and Impact of Enantiomers

On the basis of literature analysis, we have built a database containing fusion temperatures of two-component molecular cocrystals and individual compounds (1947 cocrystals/salts). In order to esti...

Design of 4-aminobenzoic acid two-component molecular crystals: prediction and experiments

Cocrystal formation of 4-aminobenzoic acid with a variety of pyrimidine, pyridine and benzamide derivatives has been investigated.

Two-component molecular crystals: relationship between the entropy term and the molecular volume of co-crystal formation

There are very few articles that investigate the thermodynamic formation of two-component molecular crystals.

Diffuse single-crystal scattering corrected for molecular form factor effects.

This paper shows that chemical short-range order in two-component molecular crystals can be solved directly by separating the influence of the molecular form factor from the diffraction pattern. This novel technique is demonstrated by analysing the diffuse scattering of tris-tert-butyl-1,3,5-benzene tricarboxamide.

Two-component molecular crystals: evaluation of the formation thermodynamics based on melting points and sublimation data

An approach to estimating co-crystal sublimation thermodynamic characteristics has been developed. The thermodynamic functions of the formation process of 281 co-crystals have been obtained and analyzed.

Evaluation of the Lattice Energy of the Two-Component Molecular Crystals Using Solid-State Density Functional Theory

The lattice energy Elatt of the two-component crystals (three co-crystals, a salt, and a hydrate) is evaluated using two schemes. The first one is based on the total energy of the crystal and its components computed using the solid-state density functional theory method with the plane-wave basis set. The second approach explores intermolecular energies estimated using the bond critical point parameters obtained from the Bader analysis of crystalline electron density or the pairwise potentials. The Elatt values of two-component crystals are found to be lower or equal to the sum of the absolute sublimation enthalpies of the pure components. The computed energies of the supramolecular synthons vary from ∼80 to ∼30 kJ/mol and decrease in the following order: acid–amide > acid–pyridine > hydroxyl–acid > amide–amide > hydroxyl–pyridine. The contributions from different types of noncovalent interactions to the Elatt value are analyzed. We found that at least 50% of the lattice energy comes from the heterosynthon and a few relatively strong H-bonds between the heterodimer and the adjacent molecules.

Design of Ferroelectric Organic Molecular Crystals with Ultrahigh Polarization

Inspired by recent successful synthesis of room-temperature ferroelectric supramolecular charge-transfer complexes, i.e., tetrathiafulvalene (TTF)- and pyromellitic diimide (PMDI)-based crystals (Tayi et al. Nature 2012, 488, 485-489), three new ferroelectric two-component organic molecular crystals are designed based on the TTF and PMDI motifs and an extensive polymorph search. To achieve energetically favorable packing structures for the crystals, a newly developed computational approach that combines polymorph predictor with density functional theory (DFT) geometry optimization is employed. Tens of thousands of packing structures for the TTF- and PMDI-based crystals are first generated based on the limited number of asymmetric units in a unit cell as well as limited common symmetry groups for organocarbon crystals. Subsequent filtering of these packing structures by comparing with the reference structures yields dozens of promising crystal structures. Further DFT optimizations allow us to identify several highly stable packing structures that possess the space group of P2₁ as well as high to ultrahigh spontaneous polarizations (23-127 μC/cm(2)) along the crystallographic b axis. These values are either comparable to or much higher than the computed value (25 μC/cm(2)) or measured value (55 μC/cm(2)) for the state-of-the-art organic supramolecular systems. The high polarization arises from the ionic displacement. We further construct surface models to derive the electric-field-switched low-symmetry structures of new TTF- and PMDI-based crystals. By comparing the high-symmetry and low-symmetry crystal structures, we find that the ferroelectric polarization of the crystals is very sensitive to atomic positions, and a small molecular displacement may result in relatively high polarizations along the a and c axes, polarity reversal, and/or electronic contribution to polarization. If these newly designed TTF- and PMDI-based crystals with high polarizations are confirmed by experiments, the computer-aided ferroelectric material design on the basis of hydrogen-bonded charge-transfer complexes with flexible electron-donor and acceptor molecules would be proven valuable for expediting the search of room-temperature "displasive-type" ferroelectric organic crystals.

X-ray powder diffraction analysis of three two-component molecular crystals: 4-chloroanilinium and chloronitrobenzoic acids

The X-ray powder diffraction patterns for three two-component molecular crystals composed of 4-chloroanilinium and chloronitrobenzoic acids with different substituted positions are reported and discussed. © 2004 International Centre for Diffraction Data.

Generation of chirality by the aggregation of column structures for two-component molecular crystals composed of chloronitrobenzoic acids and p-anisidine.

Four two-component molecular crystals 1.2, 1.3, 1.4 and 1.5 composed of chloronitrobenzoic acids and p-anisidine as components have been prepared. Among these molecular crystals, 1.2 and 1.3 showed the generation of chirality (space group P2(1)) by aggregation of mutually parallel column structures with their 2(1) axes pointing in the same direction, and the others showed no chirality. This paper shows that the generation of chirality in a molecular crystal can be explained on the basis of the aggregation of column structures and that weaker intermolecular interactions affect the generation of chiral molecular crystal.

Two-component molecular crystals composed of chloronitrobenzoic acids and 4-aminopyridine.

The crystal structures of the four isomeric organic salts 4-aminopyridinium 2-chloro-4-nitrobenzoate, (I), 4-aminopyridinium 2-chloro-5-nitrobenzoate, (II), 4-aminopyridinium 5-chloro-2-nitrobenzoate, (III), and 4-aminopyridinium 4-chloro-2-nitrobenzoate, (IV), all C(5)H(7)N(2)+ x C(7)H(3)ClNO(4)-, are presented. Compound (I) has one intramolecular hydrogen bond, one intermolecular C-H* * *O hydrogen bond and pi-pi-stacking interactions. Compound (II) has N-H* * *O, C-H* * *O and C-H* * *Cl hydrogen bonds, and Cl* * *O-C electrostatic interactions. Compound (III) has N-H* * *O and C-H* * *O hydrogen bonds. Compound (IV) has a pi-pi-stacking interaction, but no C-H* * *O hydrogen bonds.

Intermolecular interactions in the formation of two-component molecular crystals composed of chloronitrobenzoic acids and 4-benzoylpyridine

The molecular structures of six two-component molecular crystals using chloronitrobenzoic acids and 4-benzoylpyridine as components were characterized by a combination of techniques: solution NMR, solid-state IR spectra, differential scanning calorimetry (DSC) and single-crystal X-ray crystallography. The X-ray analysis revealed that the brief alternation of substituents in acid components greatly affected the packing modes of molecular crystals, and that the weaker intermolecular interactions such as C–H⋯O hydrogen bondings and π–π stacking interactions play a significant role in determining the packing modes of molecular crystals.

Two-Component Molecular Crystals Composed of Nitrobenzoic Acids and Aromatic Or Heterocyclic Bases

Slow evaporation of a solution of nitrobenzoic acids and aromatic or heterocyclic bases gave various two-component molecular crystals, which were characterized by IR spectroscopy and elemental analyses and in some case by X-ray crystallographic analysis of their single crystals.

Intermolecular Interactions And Generation of Chirality in the Formation of Two-Component Molecular Crystals between Chloronitrobenzoic Acids and 4-Benzoylpyridine Or P-Anisidine

Two-component molecular crystals using chloronitrobenzoic acids and 4-benzoylpyridine or p-anisidine as components were verified by a combination of techniques: solution NMR, solid-state IR spectra and differential scanning calorimetry (DSC) of the molecular crystals and X-ray crystallographic analysis of their single crystals.

Two-component molecular crystals from N-heteroaromatics and nitrobenzoic acids.

Five two-component molecular crystals, benzimidazolium 3-nitrobenzoate, C(7)H(7)N(2)(+).C(7)H(4)NO(4)(-), (I), benzimidazolium 4-nitrobenzoate, C(7)H(7)N(2)(+).C(7)H(4)NO(4)(-), (II), 1H-benzotriazole-3-nitrobenzoic acid (1/1), C(6)H(5)N(3).C(7)H(5)NO(4), (III), imidazolium 3-nitrobenzoate, C(3)H(5)N(2)(+).C(7)H(4)NO(4)(-), (IV), and imidazolium 4-nitrobenzoate, C(3)H(5)N(2)(+).C(7)H(4)NO(4)(-), (V), were prepared with the aim of making chiral crystals. Only (I) crystallizes in a chiral space group. The molecules of (I) and (II) are linked by hydrogen bonds to form 2(1) spiral chains. In (III), (IV) and (V), macrocyclic structures are formed from two acid and two base components, by an alternate arrangement of the acid and base moieties.

ChemInform Abstract: Solid-State Photoreaction in Two-Component Molecular Crystals of Thienylacetic Acids and Aza Aromatic Compounds.

Abstract A series of two-component molecular crystals of 2-thienylacetic acid (1) or bis(2-thienyl)acetic acid (2) with aza aromatic compounds such as acridine (a) and phenanthridine (b) were prepared by crystallization from the solutions of both components. Irradiation of the crystals caused photodecarboxylation and radical intermediates which give decarboxylated and condensation products. The relationship between the crystal structures and the reaction paths are discussed.

Generation of chirality in two-component molecular crystals from achiral molecules

Chiral co-crystals by the self-assembly of two different achiral molecules through hydrogen bonding are reviewed. The chiral crystals involve propeller-type and helical-type crystals. The chirality of the propeller-type crystals of diphenylacetic acid and aza aromatic compounds is generated from the propeller-like conformation of phenyl and carboxyl groups in the lattice. In a series of helical-type crystals of tryptamine and various achiral carboxylic acids, their chirality is generated by the formation of unidirectional two-fold helix between both components through quaternary ammonium salt bridge and hydrogen bonding. Both enantiomorphous crystals were obtained by spontaneous crystallization to give the discrimination of handedness by the solid state CD spectrometry.