Molecular Level Insights on the Liquid–Solid Transition of Large Organics by Biased Monte Carlo Simulations

The transition of computational ensembles of organic molecules from a liquid state to semi- or fully ordered solid phases, simulated by a biased Monte Carlo procedure driving the system via a forced increase of translational correlation, provide a vivid insight of molecular events accompanying the early stages of nucleation. The onset of anisotropy, conformational changes at the transition points, and the swapping of hydrogen bonds on the way to crystallization are portrayed in detail. Energy and density fluctuations are monitored and discussed in connection with molecular structure; complex flexible molecules meet a crystallization barrier in density decrease and destabilization of total configurational energy. The limitations of the procedure are amply discussed, as for optimization of force field and interpretation of the results of a biased, nonequilibrium simulation. Conclusions are given in a spectrum or reliability, from robust to tentative. In any case the procedure allows the tracing of continuous trajectories through phase space, in some cases leading to a correct reproduction of the experimental crystal structures. Force field, method, and computer programs, developed ex novo, are deposited for reproducibility

Computer Prediction of Organic Crystal Structures Using Partial X-ray Diffraction Data

This paper describes a computational procedure for the determination of complete crystal structures when the cell dimensions and space group only are known from X-ray crystallography. Molecular structure and conformation are assumed, and cannot be refined. When diffraction intensity data are available, the procedure offers an alternative to standard methods for the solution of the phase problem. The procedure applies to a wide range of organic molecules thanks to the evolution of the force field and of the computer programs. While the full ab initio prediction of crystal structures is still, in our opinion, a faraway goal, an important and fruitful application of this kind of computer modeling is in the completion of partial X-ray determinations when single crystals of suitable quality are not available, a rather frequent occurrence. Examples of this application are given, and its success implies that the need for producing good quality single crystals of newly synthesized organic compounds is nowadays less stringent, especially when only a knowledge of the intermolecular organization pattern in the crystal is sought

Computer Prediction of Organic Crystal Structures Using Partial X-ray Diffraction Data

This paper describes a computational procedure for the determination of complete crystal structures when the cell dimensions and space group only are known from X-ray crystallography. Molecular structure and conformation are assumed, and cannot be refined. When diffraction intensity data are available, the procedure offers an alternative to standard methods for the solution of the phase problem. The procedure applies to a wide range of organic molecules thanks to the evolution of the force field and of the computer programs. While the full ab initio prediction of crystal structures is still, in our opinion, a faraway goal, an important and fruitful application of this kind of computer modeling is in the completion of partial X-ray determinations when single crystals of suitable quality are not available, a rather frequent occurrence. Examples of this application are given, and its success implies that the need for producing good quality single crystals of newly synthesized organic compounds is nowadays less stringent, especially when only a knowledge of the intermolecular organization pattern in the crystal is sought

Are Racemic Crystals Favored over Homochiral Crystals by Higher Stability or by Kinetics? Insights from Comparative Studies of Crystalline Stereoisomers

The crystal and molecular structures of 134 pairs of diastereoisomers and of 279 racemic–homochiral pairs were retrieved from the Cambridge Structural Database. Lattice and intramolecular energies are calculated. Density differences between crystals of stereoisomers of all kind are mostly within 5%, as observed also for crystal polymorphs. Racemic crystals are predominantly, but not exclusively, more stable and more dense. Denser crystals are predominantly more stable, but there is no quantitative correlation between density and energy differences between partners in the chosen pairs. Second-order symmetry operators are neither ubiquitous in the racemic nor patently superior to first-order operators in promoting crystal cohesion. Thermodynamic, energetic factors in the final crystalline products are not enough to explain the (largely) predominant occurrence of racemic crystallization from racemic solution. At least for homogeneous nucleation, a probabilistic factor, from kinetics or from statistical predominance of mixed versus enantiopure aggregates, must be in action during the early separation of liquid-like particles, which are thought to be the precursors of crystal nucleation

Computer Simulations and Analysis of Structural and Energetic Features of Some Crystalline Energetic Materials

A database of 43 literature X-ray crystal structure determinations for compounds with known, or possible, energetic properties has been collected along with some sublimation enthalpies. A statistical study of these crystal structures, when compared to a sample of general organic crystals, reveals a population of anomalously short intermolecular oxygen−oxygen separations with an average crystal packing coefficient of 0.77 that differs significantly from 0.70 found for the general population. For the calculation of lattice energies, three atom−atom potential energy schemes and the semiempirical SCDS-PIXEL scheme are compared. The nature of the packing forces in these energetic materials is further analyzed by a study of the dispersive versus Coulombic contributions to overall lattice energies and to molecule−molecule energies in pairs of near neighbors in the crystals, a partitioning made possible by the unique features of the SCDS-PIXEL scheme. It is shown that dispersion forces are stronger than Coulombic forces, contrary to common belief. The low abundance of hydrogen atoms in these molecules, the close oxygen−oxygen contacts, and the high packing coefficients explain the observation that, for these energetic materials, crystal densities are anomalously high compared to those of most organic materials. However, an understanding, not to mention prediction or control, of the deeper mechanisms for the explosive power of these crystalline materials, such as the role of lattice defects, remains beyond present capabilities

Theoretical Study of Chiral Carboxylic Acids. Structural and Energetic Aspects of Crystalline and Liquid States

Lattice energy calculations by semiempirical and quantum mechanical methods have been carried out on 17 crystals of phenoxypropionic acids (PPAs), including 5 pairs of racemic and homochiral partners. Racemic crystals always consist of centrosymmetric cyclic hydrogen-bonded dimers, while homochiral crystals invariably include chain (“catemer”) motifs of O–H···O hydrogen bonds, except for one case having a pseudo-2-fold axis dimer with two molecules in the asymmetric unit. Energy differences between homochiral and racemic crystals are small, without a consistent trend of higher stability of either state. Partitioned molecule–molecule energy calculations show that hydrogen bonds compete with diffuse dispersive factors or local electrostatic interactions. Monte Carlo methods with empirical atom–atom potentials were also applied to simulate the structural and energetic equilibrium properties of some racemic and homochiral liquids. The latter are very nearly isoenergetic, apparently irrespective of molecular size, shape, and chemical constitution, and do not display significant differences in internal structure with respect to type, number, or persistency of hydrogen-bonded pairs. However, major changes in molecular conformation are predicted for PPAs upon crystallization. On the basis of these results, the roles of thermodynamics and kinetics are discussed in the context of understanding spontaneous resolution

Building Blocks of Crystal Engineering: A Large-Database Study of the Intermolecular Approach between C–H Donor Groups and O, N, Cl, or F Acceptors in Organic Crystals

The nature of CH···X interactions in organic crystals, with X being an electronegative atom, has been the subject of extensive consideration with sometimes contradictory results and ensuing opinions. We perform statistical analysis on large databases of crystal structures retrieved from the Cambridge Structural Database. Crystals containing C–H donors only are considered in conjunction with each of O, N, Cl, or F acceptors in turn. The analysis of Coulombic polarization and dispersion components reveals that the lattice energies of these crystals are largely dominated by dispersive interactions. The frequency of short H···X contacts decreases through the series CHO > CHN > CHCl > CHF, being just sporadic in the latter. The presence of such contacts is positively correlated with the Coulombic contribution to molecule–molecule interaction energies but do not generally determine the pair energy. Short CH···O or CH···N contacts are often relegated to weakly bound pairs; their minor energy contributions might be relevant for driving crystal packing of small molecules, where the contact energy is a substantial part of the lattice energy. In reproducible crystal engineering, and even more in crystal structure prediction, weak CH···X contacts are seldom responsible for the whole picture, and the wider context of competing energies should be considered

Kinetic-Bias Model for the Dynamic Simulation of Molecular Aggregation. The Liquid, Solute, Solvated-Nanodrop, and Solvated-Nanocrystal States of Benzoic Acid

A kinetically biased molecular dynamics (KB-MD) algorithm is developed as an addition to the Milano Chemistry Molecular Simulation (MiCMoS) package. Within a condensed medium, the algorithm sorts out molecular pairs coupled by a strong interaction energy and reduces their kinetic energy by a damping factor, redistributing the resulting excess among other partners within the medium. The aim is to enhance in an iterative manner the incipient intermolecular cohesion, on the way to the formation of recognition aggregates. The algorithm is applied to bulk liquid and crystalline benzoic acid, to homogeneous solutions in methanol, and to liquid or crystalline nanoclusters embedded in methanol solvent. Favorable outcomes are observed in liquid media with the formation of large molecular clusters and in the enhancement of the lifetimes of nanocrystals. Homogeneous solutions are found to require extremely long simulation times to show significant aggregation. Organization into a crystalline structure from liquid precursors is still a faraway simulation goal, but the present approach can be a useful tool, along with the introduction of appropriate collective structural variables, for tackling this long-standing problem at the atomic level

Kinetic-Bias Model for the Dynamic Simulation of Molecular Aggregation. The Liquid, Solute, Solvated-Nanodrop, and Solvated-Nanocrystal States of Benzoic Acid

A kinetically biased molecular dynamics (KB-MD) algorithm is developed as an addition to the Milano Chemistry Molecular Simulation (MiCMoS) package. Within a condensed medium, the algorithm sorts out molecular pairs coupled by a strong interaction energy and reduces their kinetic energy by a damping factor, redistributing the resulting excess among other partners within the medium. The aim is to enhance in an iterative manner the incipient intermolecular cohesion, on the way to the formation of recognition aggregates. The algorithm is applied to bulk liquid and crystalline benzoic acid, to homogeneous solutions in methanol, and to liquid or crystalline nanoclusters embedded in methanol solvent. Favorable outcomes are observed in liquid media with the formation of large molecular clusters and in the enhancement of the lifetimes of nanocrystals. Homogeneous solutions are found to require extremely long simulation times to show significant aggregation. Organization into a crystalline structure from liquid precursors is still a faraway simulation goal, but the present approach can be a useful tool, along with the introduction of appropriate collective structural variables, for tackling this long-standing problem at the atomic level