Long-range Supramolecular Synthon Polymorphism: A Case Study of Two New Polymorphic Cocrystals of Ph2Te2 – 1,4-C6F4I2

Along with the reported earlier co-crystal of diphenyl ditelluride (Ph2Te2) and halogen bond donor 1,4-diiodo-tetrafluorobenzene (p-DITFB) 1α, its two new polymorphic forms (1β and 1γ) present a rare case of...

Oxonium trans-bis(oxalato)rhodate and related sodium salts: a rare example of crystalline complex acid

New coordination compounds trans-bis(oxalato)diaquarhodiate sodium dihydrate Na[Rh(H2O)2Ox2]·2H2O (crystallizes in two polymorphic forms NaRh-1 and NaRh-2), trans-bis(oxalato)hydroxoaquarhodiate sodium tetrahydrate Na2[Rh(H2O)(OH)Ox2]·4H2O (Na2Rh) and trans-bis(oxalato)diaquarhodic acid tetrahydrate (H3O)[Rh(H2O)2Ox2]·4H2O (HRh) are synthesized. The compounds are characterized by IR spectroscopy, elemental analysis and single crystal X-ray diffraction. NaRh-1, NaRh-2 and Na2Rh crystallize in space group P 1. Trans-bis(oxalato)diaquarhodic acid exists not only in solution, but can also crystallize as a tetrahydrate (space group C2/c). The formation of various species in solution of rhodium hydroxide in oxalic acid and their redistribution were studied using 103Rh NMR spectroscopy.

Influence of Crystallization Additives on Morphology of Selected Benzoic Acids - A Molecular Dynamics (MD) Simulation Study

The possibility to modify the morphology by crystallization additives of model substances was studied using molecular dynamics simulations. For this 2,6-dimethoxybenzoic acid and 3-hydroxybenzoic acid, each having two polymorphic forms, including a form without carboxylic acid homodimers in their crystal structure were selected. For each polymorph 2-3 largest crystal faces were selected for the study and the crystal was cut along these planes by preparing a simulation box with these planes facing towards solution containing additives. In the performed study it was evaluated which additives potentially can influence the crystal morphology and possibly also polymorph obtained in the crystallization by significantly changing the growth rate of crystal by adsorbing on the surface. For the study 4-5 additives providing different intermolecular interaction possibilities were selected. Among the studied additives urea showed the most complete adsorption and the longest residence time on surfaces of both substances, with the exceptions of few specific planes.

Superexchange interactions in AgMF4 (M = Co, Ni, Cu) polymorphs

Magnetic properties of silver(II) compounds have been of interest in recent years. In covalent compounds, the main mechanism of interaction between paramagnetic sites is the superexchange via the connecting ligand. To date, little is known of magnetic interactions between Ag(II) cations and other paramagnetic centres. It is because only a few compounds bearing a Ag(II) cation and other paramagnetic transition metal cation are known from experimental work. Recently the high-pressure synthesis of ternary silver(II) fluoridometallates with 3d metal cations AgMF4 (M = Co, Ni, Cu) was predicted to be feasible. Here, we investigate the magnetic properties of these compounds in their diverse polymorphic forms. Using well-established computational methods we predict superexchange pathways in AgMF4 compounds, evaluate coupling constants and calculate the impact of the Ag(II) presence on superexchange between the other cations. The results indicate that the low-pressure form of AgCuF4, the only one composed of stacked layers like the parent AgF2, would show mainly Ag–Ag and Cu–Cu superexchange interactions. Upon compression, or with the nickel(II) cation, the Ag–M interactions in AgMF4 compounds are intensified, which is emphasized by an increase of Ag–M superexchange coupling constants and Ag–F–M angles. All the strongest Ag–M superexchange pathways are quasi-linear, leading to the formation of antiferromagnetic chains along the crystallographic directions. The impact of Ag(II) on M–M superexchange turns out to be moderate, due to factors connected to the crystal structure.

New Insights into the Crystallographic Disorder in the Polymorphic Forms of Aspirin from Low-frequency Vibrational Analysis

Terahertz time-domain spectroscopy (THz-TDS) is applied to two polymorphs of acetylsalicylic acid (aspirin), and the experimental spectra are compared to lattice dynamical calculations using high accuracy density functional theory (DFT). The calculations confirm that forms I and II have very close energetic and thermodynamic properties, and also that they show similar spectral features in the far-infrared region, reflecting the high degree of similarity in their crystal structures. Unique vibrational modes are identified for each polymorph which allow them to be distinguished using THz-TDS measurements. The observation of spectral features attributable to both polymorphic forms in a single sample, however, provides further evidence to support the hypothesis that crystalline aspirin typically comprises intergrown domains of forms I and II. Differences observed in the baseline of the measured THz-TDS spectra indicate a greater degree of structural disorder in samples of form II. Calculated Gibbs free energy curves show a turning point at 75 K, inferring that form II is expected to be more stable than form I above this temperature, as a result of its greater vibrational entropy. The calculations do not account for any differences in configurational entropy that may arise from expected structural defects. Further computational work on these structures, such as ab initio molecular dynamics (AIMD), would be very useful to further explore this perspective.

Structures of a Phosphoryl Derivative of 4-Allyl-2,4-dihydro-3H-1,2,4-triazole-3-thione: An Illustrative Example of Conformational Polymorphism

Two polymorphic forms of a conformationally flexible molecule, 5-[(Diphenylphosphoryl)methyl]-4-(prop-2-en-1-yl)-2,4-dihydro-3H-1,2,4-triazole-3-thione, were obtained by crystallization and characterized by X-ray diffraction analysis and differential scanning calorimetry. The relative stability of polymorphic forms was estimated with DFT calculations of crystal structures and isolated molecules. It turns out, that in the first more dense polymorph with higher cohesion energy and crystal lattice energy, the molecule adopts an energetically unfavorable conformation, and forms dimers with lower H-bond strength, as compared to the second polymorph. On the other hand, in the second polymorph, the molecule adopts almost the lowest-energy conformation and forms infinite chains via strong H-bonds. The first form that seems to be more thermodynamically stable at room temperature transforms into the second form via two endothermic phase transitions; the apparent irreversibility of the transition is due to high energy difference between the molecular conformations in crystals.

The influence of lipid digestion on the fate of orally administered drug delivery vehicles

This review will focus on orally administered lipid-based drug delivery vehicles and specifically the influence of lipid digestion on the structure of the carrier lipids and their entrained drug cargoes. Digestion of the formulation lipids, which are typically apolar triglycerides, generates amphiphilic monoglycerides and fatty acids that can self-assemble into a diverse array of liquid crystalline structures. Tracking the dynamic changes in self-assembly of the lipid digestion products during digestion has recently been made possible using synchrotron-based small angle X-ray scattering. The influence of lipid chain length and degree of unsaturation on the resulting lipid structuring will be described in the context of the critical packing parameter theory. The chemical and structural transformation of the formulation lipids can also have a dramatic impact on the physical state of drugs co-administered with the formulation. It is often assumed that the best strategy for drug development is to maximise drug solubility in the undigested formulation lipids and to incorporate additives to maintain drug solubility during digestion. However, it is possible to improve drug absorption using lipid digestion in cases where the solubility of the dosed drug or one of its polymorphic forms is greater in the digested lipids. Three different fates for drugs administered with digestible lipid-based formulations will be discussed: (1) where the drug is more soluble in the undigested formulation lipids; (2) where the drug undergoes a polymorphic transformation during lipid digestion; and (3) where the drug is more soluble in the digested formulation lipids.