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

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

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

Why Is α‑d‑Glucose Monomorphic? Insights from Accurate Experimental Charge Density at 90 K

d-glucose is a strategic chemical for agri-food and pharma industries, which are now exploiting an expected increase of 5% in the global investment round from 2020 to 2028. Despite such a broad industrial interest, the reasons behind room-p monomorphism in d-glucose are unclear. The crystal structure of α-d-glucose is provided here with an unprecedented resolution (0.46 Å) by single-crystal X-ray diffraction at T = 90(1) K. Occurrence of anomeric disorder in the α phase, which has not been reported to date, is demonstrated. The topological analysis of the total charge density distribution is also carried out within the framework of Bader’s Quantum Theory of Atoms in Molecules, allowing to rank the relative strength of hydrogen bonds in the crystal structure. It is found that most OH···O contacts have a significant covalent character and build up an exceptionally stiff three-dimensional hydrogen bond network. On the one hand, this locks the molecular conformation by hampering the rotational flexibility of the hydroxy substituents. On the other hand, favorable recognition modes, based on the interaction of the charge density distributions of glucose molecules, cooperatively account for the lattice cohesion. A change in the relative orientation of OH groups would affect the crystal cohesion by changing locally the molecular electrostatic potential, V(r)

Synthesis, X-ray, and NMR Studies on Palladium BINAP Complexes Containing Oxazolidinone and Acetylacetonate Anions

A series of monocationic palladium BINAP complexes, [Pd(rac-BINAP)(an oxazolidinone anion)][X] and [Pd(rac-BINAP)(an acetylacetonate anion)][X] (X = a, CF3SO3-; b, BF4-) (9−13), have been synthesized and characterized. A dicationic intermediate, pertinent to the Pd-catalyzed hydroamination reaction, arising from the reaction of the bis-aquo complex [Pd(H2O)2(rac-BINAP)]2(CF3SO3)2 and 1 equiv of an oxazolidinone, has been characterized via low-temperature NMR studies. The structures of the complexes [Pd(rac-BINAP)(CH3−C(O)−C(CH3)−C(O)−CH3)](BF4), 12b, and [Pd(μ-OH)(rac-BINAP)]2(CF3SO3)2 have been determined by X-ray diffraction. The solid-state structures of two separate forms of the BF4- salt 12b were obtained. One form of the salt can be thought of as a tight ion pair, whereas the second form contains a dichloromethane solvent molecule, packed in approximately a fifth coordination position together with a relatively remote BF4- anion. These structures represent a rare example where both ion pairing and strong solvation could be individually characterized. PGSE diffusion coefficients (D values) were measured for both the CF3SO3- and BF4- salts of 9−13 in CD2Cl2. In addition, D values were obtained for the CF3SO3- salts in THF and CDCl3 solutions. The amount of ion pairing decreases in the sequence CDCl3 > THF > CD2Cl2. The 1H,19F-HOESY spectra for the salts in CDCl3 suggest that the CF3SO3- is approaching the positive metal and phosphorus centers via a pathway that brings it closest to the P-phenyl groups but remote from the chelating anion

Structure, Bonding, and Dynamics of Several Palladium η³-Allyl Carbene Complexes

A series of Pd-allyl carbene complexes, [PdX(η3-C3H5)(IPr)], 1 (X = a, Cl−, b, Br−, c, I−, d, N3−, e, NCO−, f, SCN−, g, CN−, h, OAc−, i, OTf−, j, 4-Me-pyridine), have been studied by one- and two-dimensional NMR techniques. 13C, 1H, and phase-sensitive NOE NMR studies on these relatively simple complexes reveal that (a) the trans influence of the carbene carbon in 1 seems to be smaller than that found for PPh3 and other P-donor ligands, (b) the selective η3−η1 opening of the allyl is under electronic control, and (c) the rates of η3−η1 allyl isomerization depend on the X ligand. The solid-state structure of 1c is reported, as well as selected 15N chemical shift data for the coordinated carbene ligand

X-ray Diffraction, PGSE Diffusion, and Related NMR Studies on a Series of Cp*-Based Ru(IV)(Cp*)(η³-CH₂−CH−CHPh) Allyl Complexes

The new ruthenium (IV) allyl complexes [Ru(Cp*)Cl(DMF)(η3-CH2−CH−CHPh)](PF6) (2b) and [Ru(Cp*)Cl(t-BuCN)(η3-CH2−CH−CHPh)](PF6) (2c) have been prepared and their structures determined. These results are compared with the analogous X-ray data for [Ru(Cp*)Cl(CH3CN)(η3-CH2−CH−CHPh)](PF6), [Ru(Cp*){OC(O-t-Bu)O}(η3-CH2−CH−CHPh)](PF6), [Ru(Cp*)(CH3CN)2(η3-CH2−CH−CHPh)](PF6)2, and [Ru(Cp*)(DMF)2(η3-CH2−CH−CHPh)](PF6)2. In all of the structures, the Ru−((η3-CH2−CH−CHPh) moiety is markedly distorted such that Ru−CPh(allyl) separation is much longer than the remaining two Ru−C(allyl) distances. The DMF and acetonitrile ligands are shown to exchange on the NMR time scale via both variable-temperature and 2-D exchange spectroscopy. Pulsed gradient spin−echo (PGSE) diffusion and 1H,19F HOESY NMR methods show that there is relatively little ion pairing in these salts in DMF and acetonitrile solutions. The PF6 anions take up specific positions with respect to the Ru(IV) cations

Structure, Bonding, and Dynamics of Several Palladium η³-Allyl Carbene Complexes

A series of Pd-allyl carbene complexes, [PdX(η3-C3H5)(IPr)], 1 (X = a, Cl−, b, Br−, c, I−, d, N3−, e, NCO−, f, SCN−, g, CN−, h, OAc−, i, OTf−, j, 4-Me-pyridine), have been studied by one- and two-dimensional NMR techniques. 13C, 1H, and phase-sensitive NOE NMR studies on these relatively simple complexes reveal that (a) the trans influence of the carbene carbon in 1 seems to be smaller than that found for PPh3 and other P-donor ligands, (b) the selective η3−η1 opening of the allyl is under electronic control, and (c) the rates of η3−η1 allyl isomerization depend on the X ligand. The solid-state structure of 1c is reported, as well as selected 15N chemical shift data for the coordinated carbene ligand

Palladium-Allyl Phosphoramidite Complexes: Solid-State Structures and Solution Dynamics

Several mono-phosphoramidite and bis-phosphoramidite 2-methallyl and 1,3-diphenylallyl allyl complexes of Pd(II) have been prepared. The solid-state structure for one of these has been determined. The mono-phosphoramidite chloro-allyl complexes of Pd(II) exist in two isomeric forms in solution. 1H,1H NMR exchange spectroscopy reveals that the dinuclear species [Pd(μ-Cl)(η3-CH2C(Me)CH2)]2 is involved in the interconversion between the two isomers. There is evidence to suggest that phosphoramidite dissociation is not responsible for this exchange. The cationic η3-2-methallyl bis-phosphoramidite Pd complexes reveal nonequivalent 31P resonances, as a consequence of slow allyl dynamics and in agreement with the preliminary X-ray structure