No abstract

The relevant noncovalent interaction patterns responsible for intermolecular recognition of the antiplasmodial chloroquine (CQ) in its bioactive diprotonated form, CQH 2 2+ , are investigated. Chloroquine dihydrogen phosphate hydrated salt (P2 1 /c) was crystallized by gel diffusion. A highresolution single-crystal X-ray diffraction experiment was performed at 103(2) K, and a density functional theory model for the in-crystal electron density was derived, allowing the estimation of the interaction energies in relevant molecular pairs. H 2 PO 4 − ions form infinite chains parallel to the monoclinic axis, setting up strong NH•••O charge-assisted hydrogen bonds (CAHBs) with CQH 2 2+ . Couples of facing protonated quinoline rings are packed in a π•••π stacked arrangement, whose contribution to the interaction energy is very low in the crystal and completely overwhelmed by Coulomb repulsion between positive aromatic rings. This questions the ability of CQ in setting up similar stacking interactions with the positively charged Fe-protoporphyrin moiety of the heme substrate in solution. When the heme/CQ adduct incorporates a Fe−N coordinative bond, stronger π•••π interactions are instead established due to the lacking of net electrostatic repulsions. Yet, CAHBs among the protonated tertiary amine of CQ and the propionate group of heme still provide the leading stabilizing effect. Implications on possible modifications/improvements of the CQ pharmacophore are discussed.

We present an accurate investigation of the prototypical rare-earth cobaltite GdBaCo 2 O 5.0 by complementary synchrotron powder and conventional source single-crystal x-ray diffraction experiments. The correct space group (Pmmm) and the accurate crystallographic structure of this compound at room temperature (RT) have been determined. By increasing T a second-order structural-phase transition to a tetragonal structure with space group P4/mmm at T ≈ 331 K is found. Close to the Néel temperature (T N ≈ 350 K), anomalies appear in the trend of the lattice constants, suggesting that the structural phase transition is incipient at T N . A possible mechanism for this complex behavior is suggested.

Dichloro-p-benzoquinone (DCBQ) has been investigated by single-crystal X-ray diffraction experiments in the T range of 300−21 K and quantum-mechanical simulations. A reversible monoclinic (high-T) to triclinic (low-T) phase transition has been detected at T c = 122.6(5) K. The various noncovalent interactions (NCIs) that determine the solid-state selfrecognition of DCBQ have been characterized as a function of T through the quantum theory of atoms in molecules. On lowering T, carbonyl−carbonyl interactions progressively strengthen, inducing a change in the crystal structure, while the dipolar C−Cl•••OC NCIs and the relatively strong Cl•••Cl halogen bonds (XBs) and CH•••O hydrogen bonds play an essential, but ancillary, role. Dispersive forces cooperate with other closed-shell dipolar NCIs, and particularly with XBs, in determining their overall attractive character, even when bulky and positively charged chlorine atoms are drawn closer and closer at low temperatures. The intermolecular interaction energies have been evaluated above and below T c as sums of electrostatic, repulsion, and dispersion contributions.

The total charge density of PYRAC, a polar (Pca21) organic racemate with Z' = 2 was derived from high-resolution single-crystal X-ray diffraction data at T = 100(2) K and periodic DFT calculations.The PYRAC asymmetric unit consists of a hydrogen-bonded pair of conformationally different enantiomers, A and Bi, where the subscript 'i' indicates a reversed absolute configuration. The lattice stability was compared with that of centrosymmetric possibly competing structures, with the aim of understanding why a non-centrosymmetric lattice framework is obtained from a racemic mixture. The likelihood of specific intermolecular recognition processes among different conformers of PYRAC in the very first stages of nucleation was investigated by DFT simulations in vacuo. Two competing, equivalent interconversion pseudorotatory paths between the most stable A and the least stable B conformers were found. It results that molecules spend most of their time (≈ 53 %) in the A conformation, while the B one is far less populated (≈ 7 %). Therefore, centrosymmetric AAi adducts are formed very frequently in the reaction liquor, while the BBi ones are rare. Nevertheless, AAi pairs produce crystal forms with cohesive energies and densities significantly less favourable than those estimated for the non-centrosymmetric heterochiral ABi ones. Therefore, preference for Z' = 2 in conjunction with non-centrosymmetric point and space groups results from the thermodynamic control of the crystallization process. The capability of forming extended hydrogen bond chains throughout the lattice appears to be a prerequisite to bind together the fundamental ABi repeating units.