Phase Transitions Involving Channel Hydrates of a New Pharmaceutical Compound.

Introduction: Hydrates are often used as pharmaceutical active pharmaceutical ingredients (API), especially when anhydrates may not be feasible likely due to physicochemical properties concerns. Pharmaceutical hydrates, whereas water is present as crystal adduct, are feasible for drug products as they do not pose any safety concern. Hydrates can impart many different advantages; therefore, they are quite common and preferred solid forms for numerous pharmaceutical materials on market.

Computational and Experimental Screening Approaches to Aripiprazole Salt Crystallization.

Introduction: The screening of multicomponent crystal system (MCC) is a key method for improving physicochemical properties of active pharmaceutical ingredients (APIs). The challenges associated with experimental salt screening include a large number of potential counterions and solvent systems and tendency to undergo disproportionation to produce free form during crystallization. These challenges may be mitigated by a combination of experimental and computational approaches to salt screening.

Absolute Configuration Determination of Chiral API Molecules by MicroED Analysis of Cocrystal Powders Formed Based on Cocrystal Propensity Prediction Calculations.

Establishing the absolute configuration of chiral active pharmaceutical ingredients (APIs) is of great importance. Single crystal X-ray diffraction (scXRD) has traditionally been the method of choice for such analysis, but scXRD requires the growth of large crystals, which can be challenging. Here, we present a method for determining absolute configuration that does not rely on the growth of large crystals.

pH-Dependent supersaturation from amorphous solid dispersions of weakly basic drugs.

Purpose: In amorphous solid dispersions (ASDs), the chemical potential of a drug can be reduced due to mixing with the polymer in the solid matrix, and this can lead to reduced drug release when the polymer is insoluble in the dissolution media. If both the drug and the polymer composing an ASD are ionizable, drug release from the ASD becomes pH-dependent. The goal of this study was to gain insights into the pH-dependent solubility suppression from ASD formulations.

Accelerating pre-formulation investigations in early drug product life cycles using predictive methodologies and computational algorithms.

Precisely developed computational methodologies can allow the drug product lifecycle process to be time-efficient, cost-effective and reliable through a thorough fundamental understanding at the molecular level. Computational methodologies include computational simulations, virtual screening, mathematical modeling and predictive tools. In light of current trends and increased expectations of product discovery in early pharmaceutical development, we have discussed different case studies.

Crystal form control and particle size control of RG3487, a nicotinic α7 receptor partial agonist.

This paper describes solid form control and particle size control of RG3487, a nicotinic receptor partial agonist. Four crystal forms were identified by polymorph screen under ∼100 varying conditions. Form A and Form B are anhydrates, while Forms C and D are solvates.

Synthesis and structural characterization of Cu(I) and Ni(II) complexes that contain the bis[2-(diphenylphosphino)phenyl]ether ligand. Novel emission properties for the Cu(I) species.

The pseudotetrahedral complexes [Cu(NN)(DPEphos)]BF(4), where DPEphos = bis[2-(diphenylphosphino)phenyl]ether and NN = 1,10-phenanthroline (1), 2,9-dimethyl-1,10-phenanthroline (2), 2,9-di-n-butylphenanthroline (3), or two dimethylcyanamides (4), and NiCl(2)(DPEphos) (5) have been synthesized and structurally characterized by X-ray crystallography and their solution properties examined by use of a combination of cyclic voltammetry, NMR spectroscopy, and electronic absorption spectroscopy. Complexes 1-4 possess a reversible Cu(II)/Cu(I) couple at potentials upward of +1.2 V versus Ag/AgCl.

A new type of tweezer complex involving a rhenium-rhenium multiple bond that enforces an unusual structure in a dipalladium(II) unit.

The substitution of the mu-acetato ligands in cis-Re(2)(mu-O(2)CCH(3))(2)Cl(2)(mu-dppm)(2) (1, dppm = Ph(2)PCH(2)PPh(2)) and trans-Re(2)(mu-O(2)CCH(3))(2)Cl(2)(mu-dppE)(2) (2, dppE = Ph(2)PC(=CH(2))PPh(2)) by [4-Ph(2)PC(6)H(4)CO(2)](-) occurs with retention of stereochemistry to give cis-Re(2)(mu-O(2)CC(6)H(4)-4-PPh(2))(2)Cl(2)(mu-dppm)(2) (3) and trans-Re(2)(mu-O(2)CC(6)H(4)-4-PPh(2))(2)Cl(2)(mu-dppE)(2) (6), respectively. The uncoordinated phosphine groups in complexes 3 and 6 have been used to form mixed-metal assemblies with Au(I) and Pd(II), including the Re(2)Pd(2) complex cis-Re(2)(mu-O(2)CC(6)H(4)-4-PPh(2))(2)Cl(2)(mu-dppm)(2)(Pd(2)Cl(4)) (5), in which the planar [(P)ClPd(mu-Cl)(2)PdCl(P)] unit has the unusual cis structure. The crystal structures of 3 and 5 have been determined.

Unsymmetrical dirhenium complexes that contain [Re(2)](6+) and [Re(2)](5+) cores complexed by tridentate ligands with P(2)O and P(2)N donor sets.

The quadruply bonded dirhenium(III) complex (n-Bu(4)N)(2)Re(2)Cl(8) reacts with tridentate ligands that contain essentially planar P,O,P donor sets to afford the complexes Re(2)Cl(6)(eta(3)-L(1)) (3) (L(1) = bis[2-(diphenylphosphino)phenyl]ether) and (n-Bu(4)N)[Re(2)Cl(7)(eta(1)-L(2))] (4) (L(2) = 4,6-bis(diphenylphosphino)dibenzofuran). Spectroscopic and electrochemical data support the unsymmetrical structure Cl(4)ReReCl(2)(eta(3)-L(1)) in the case of 3, while 4 contains monodentate P-bound L(2) both complexes contain Re---Re bonds. The synthon cis-Re(2)(mu-O(2)CCH(3))(2)Cl(4)(H(2)O)(2) reacts with ligands L(1), L(2), 2,6-bis(diphenylphosphinomethyl)pyridine (L(3)), bis[2-(diphenylphosphino)ethyl]amine (L(4)), and N,N-bis[2-(diphenylphosphino)ethyl]trimethylacetamide (L(5)) to give the paramagnetic complexes Re(2)(mu-O(2)CCH(3))Cl(4)(eta(3)-L(n)) (5-9) with Re bonds.

Simple Cu(I) complexes with unprecedented excited-state lifetimes.

This report describes new, readily accessible copper(I) complexes that can exhibit unusually long-lived, high quantum yield emissions in fluid solution. The complexes are of the form [Cu(NN)(POP)]+ where NN denotes 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,9-di-n-butyl-1,10-phenanthroline (dbp) and POP denotes bis[2-(diphenylphosphino)phenyl] ether. Modes of characterization include X-ray crystallography and cyclic voltammetry.