Ghazala Sadiq

The utility of a ternary phase diagram in the discovery of new co-crystal forms

The construction of the ternary phase diagram urea–glutaric acid–water has led to the discovery of a new co-crystal form.

Crystallography Aided by Atomic Core-Level Binding Energies: Proton Transfer versus Hydrogen Bonding in Organic Crystal Structures

Ionic bond or hydrogen bridge? Brønsted proton transfer to nitrogen acceptors in organic crystals causes strong N1s core-level binding energy shifts. A study of 15 organic cocrystal and salt systems shows that standard X-ray photoelectron spectroscopy (XPS) can be used as a complementary method to X-ray crystallography for distinguishing proton transfer from H-bonding in organic condensed matter.

Crystallising trimesic acid from DMSO solutions – can crystallography teach us anything about the process of crystal nucleation?

Using combined X-ray diffraction and FTIR spectroscopy, a remarkable similarity is revealed between the local environments of trimesic acid in solution and in its most metastable trisolvate with DMSO. The implications of this for the nature of the nucleation process are discussed.

The coordination chemistry of perfluorovinyl substituted phosphine ligands, a crystallographic and spectroscopic study. Co-crystallisation of both cis- and trans-isomers of [PtCl2{PiPr2(CFCF2)}2] within the same unit cell

The coordination chemistry of the perfluorovinyl phosphines PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy,(CF=CF2) and PPh(CF=CF2)2 to rhodium(I), palladium(II), and platinum(II) centres has been investigated. The electronic properties of the ligands are estimated based on v(CO) and 1J(Rh-P) values. X-Ray diffraction data for the square-planar Pd(II) and Pt(II) perfluorovinyl-phosphine containing complexes allow estimates of the steric demand for the series of ligands PPh2(CF=CF2), PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy2(CF=CF2) and PPh(CF=CF2)2 to be determined. The (CF=CF2) fragment is found to be more electron withdrawing than (C6F5) yet sterically less demanding. These ligands therefore provide a range of electron-neutral to phosphite-like electronic properties combined with a range of steric demands. This study also reveals that short intramolecular interactions from the metal centre to the beta-fluorine atom cis to phosphorus of the CF=CF2 groups are observed in all-trans square planar complexes of the ligands. Unusually, the complex [PtCl2{P(i)Pr2(CF=CF2)}2] crystallises with both cis- and trans-isomers present in the unit cell. It appears that co-crystallisation of both isomers occurs in order to maximise fluorous regions in the crystal packing, and the extended structure displays short fluorine-fluorine contacts. The generation of mixed geometries seems to be a phenomenon of crystallisation, as solution phase NMR studies reveal the presence of only the trans-isomer.

The isolation of a metastable conglomerate using a combined computational and controlled crystallization approach

While the use of additives to control the crystallization of polymorphs is well known, similar methodology to promote the crystallization of a metastable conglomerate over a stable racemic compound in enantiomeric systems has not been reported. Here we demonstrate this phenomenon in the case of 2-chloromandelic acid.

H-bonds and Protons in Molecular Crystals: Insight from Combined XPS/ssNMR/XRD

Physicochemical properties of molecular crystals are significantly influenced by non-covalent interactions and proton transfer. A well known application is the tuning of solubility, bioavailability and stability of pharmaceutical actives through co-crystal (hydrogenbonding) or salt (ionic, Brønsted acceptors) formation. X-ray Photoelectron Spectroscopy (XPS) is an intrinsically local structural probe, providing information on the chemical state and chemical environment of atoms in molecules and crystals through the photoemission of core level electrons. We have recently studied a wide range of acid-base complexes in molecular crystals and found that analyzing the chemical shifts of N1s core level binding energies provides a facile route for characterizing the chemical and structural changes at functional groups involved in hydrogen bonding and proton transfer [1]. Very importantly, XPS unequivocally distinguishes protonated (salt) from hydrogen-bonded (co-crystal) nitrogen moieties. We have complemented our results for nitrogen species with 15N SolidState Nuclear Magnetic Resonance (ssNMR) chemical shifts, which reveal low frequency shifts with protonation, but the magnitude of these shifts is additionally influenced by the wider chemical environment [2]. When crystallographic structure information is available, ssNMR shifts can be computationally predicted and thereby related to H-bond lengths, giving a measure of H-bond strength (NMR crystallography). The wide variety of donor/acceptor systems we have investigated has covered a large range of pKa values and demonstrates the generic nature of taking an XPS/ssNMR/XRD approach to organic molecule crystallography (Fig 1). The excellent agreement between the conclusions drawn by XPS and combined ssNMR/CASTEP investigations opens up a reliable avenue for local structure characterization in molecular systems even in the absence of crystal structure information, for example with non-crystalline or amorphous matter.

Core level crystallography: Probing H-bonding through nitrogen XPS and NEXAFS

J. Stevens, S. Byard, L. Newton, C. Jaye, C. Seaton, G. Sadiq, D. Fischer, R. Davey, S. Schroeder The University of Manchester, School of Chemical Engineering and Analytical Science, Manchester, UK, Covance, Analytical Sciences, Alnwick, UK, National Institute of Standards and Technology, Synchrotron Methods Group, Gaithersburg, USA, The University of Manchester, School of Chemistry, Manchester, UK