Stephen A. Moggach

A potent cytotoxic photoactivated platinum complex

We show by x-ray crystallography that the complex trans, trans, trans-[Pt(N3)2(OH)2(NH3)(py)] (1) contains an octahedral PtIV center with almost linear azido ligands. Complex 1 is remarkably stable in the dark, even in the presence of cellular reducing agents such as glutathione, but readily undergoes photoinduced ligand substitution and photoreduction reactions. When 1 is photoactivated in cells, it is highly toxic: 13–80 x more cytotoxic than the PtII anticancer drug cisplatin, and ca. 15 x more cytotoxic toward cisplatin-resistant human ovarian cancer cells. Cisplatin targets DNA, and DNA platination levels induced in HaCaT skin cells by 1 were similar to those of cisplatin. However, cisplatin forms mainly intrastrand cis diguanine cross-links on DNA between neighboring nucleotides, whereas photoactivated complex 1 rapidly forms unusual trans azido/guanine, and then trans diguanine PtII adducts, which are probably mainly intrastrand cross-links between two guanines separated by a third base. DNA interstrand and DNA–protein cross-links were also detected. Importantly, DNA repair synthesis on plasmid DNA platinated by photoactivated 1 was markedly lower than for cisplatin or its isomer transplatin (an inactive complex). Single-cell electrophoresis experiments also demonstrated that the DNA damage is different from that induced by cisplatin or transplatin. Cell death is not solely dependent on activation of the caspase 3 pathway, and, in contrast to cisplatin, p53 protein did not accumulate in cells after photosensitization of 1. The trans diazido PtIV complex 1 therefore has remarkable properties and is a candidate for use in photoactivated cancer chemotherapy.

Mechanical Properties of Dense Zeolitic Imidazolate Frameworks (ZIFs): A High-Pressure X-ray Diffraction, Nanoindentation and Computational Study of the Zinc Framework Zn(Im)(2), and its Lithium-Boron Analogue, LiB(Im)(4)

The dense, anhydrous zeolitic imidazolate frameworks (ZIFs), Zn(Im)(2) (1) and LiB(Im)(4) (2), adopt the same zni topology and differ only in terms of the inorganic species present in their structures. Their mechanical properties (specifically the Youngs and bulk moduli, along with the hardness) have been elucidated by using high pressure, synchrotron X-ray diffraction, density functional calculations and nanoindentation studies. Under hydrostatic pressure, framework 2 undergoes a phase transition at 1.69 GPa, which is somewhat higher than the transition previously reported in 1. The Youngs modulus (E) and hardness (H) of 1 (E≈8.5, H≈1 GPa) is substantially higher than that of 2 (E≈3, H≈0.1 GPa), whilst its bulk modulus is relatively lower (≈14 GPa cf. ≈16.6 GPa). The heavier, zinc-containing material was also found to be significantly harder than its light analogue. The differential behaviour of the two materials is discussed in terms of the smaller pore volume of 2 and the greater flexibility of the LiN(4) tetrathedron compared with the ZnN(4) and BN(4) units.

High-pressure polymorphism in amino acids

Pressure up to 10 GPa is a powerful method for studying polymorphism in organic crystal structures, and this review surveys work carried out on high-pressure polymorphism in amino acids. High-pressure polymorphs have been established crystallographically for glycine, alanine, serine, cysteine and leucine. Phase transitions can be driven by the avoidance of very short intermolecular contacts or by promotion of a more stable molecular conformation. Experimental methods are also briefly surveyed, along with three methods that have proved very helpful in the analysis of high-pressure polymorphs, namely the PIXEL method for calculation of intermolecular energies, topological analysis with Voronoi–Dirichlet partitioning and Hirshfeld surfaces for gaining a graphical overview of intermolecular interactions.

High-pressure polymorphism in L-cysteine: the crystal structures of L-cysteine-III and L-cysteine-IV.

The crystal structure of the orthorhombic phase of L-cysteine (hereafter L-cysteine-I) consists of chains of molecules linked via NH...O hydrogen bonds. The chains are linked into a layer by other NH...O hydrogen bonds, forming R4(4)(16) ring motifs. The layers are linked by further NH...O and disordered SH...S/SH...O interactions. The main effects of compression to 1.8 GPa are to contract voids in the middle of the R4(4)(16) rings and to reduce S...S distances from 3.8457 (10) to 3.450 (4) angstroms. The latter is at the lower limit for S...S distances and we suggest that strain about the S atom is responsible for the formation of a new phase of L-cysteine, L-cysteine-III, above 1.8 GPa. The phase transition is accompanied by a change in the NCCS torsion angle from ca 60 to ca -60 degrees and small positional displacements, but with no major changes in the orientations of the molecules. The structure of L-cysteine-III contains similar R-type ring motifs to L-cysteine-I, but there are no S...S contacts within 3.6 angstroms. L-Cysteine-III was found to be stable to at least 4.2 GPa. On decompression to 1.7 GPa, another single-crystal to single-crystal phase transition formed another previously uncharacterized phase, L-cysteine-IV. This phase is not observed on increasing pressure. The structure consists of two crystallographically independent cysteine molecules in the same conformations as those found in L-cysteine-I and L-cysteine-III. The structure separates into zones with are alternately phase I-like and phase III-like. L-Cysteine-IV can therefore be thought of as an unusual example of an intermediate phase. Further decompression to ambient pressure generates L-cysteine-I.

Incorporation of a new design of backing seat and anvil in a Merrill–Bassett diamond anvil cell

A modification to the Merrill–Bassett miniature diamond anvil cell is reported here, with the inclusion of tungsten carbide backing seats with Boehler–Almax-cut diamonds to replace the previously used beryllium seats and (typically) modified brilliant-cut anvils. This has led to the removal of troublesome beryllium powder lines from diffraction images, while maintaining the pressure range and opening angle of the original design.

Temperature- and Pressure-induced Proton Transfer in the 1:1 Adduct Formed between Squaric Acid and 4,4 '-Bipyridine

We have applied a combination of spectroscopic and diffraction methods to study the adduct formed between squaric acid and bypridine, which has been postulated to exhibit proton transfer associated with a single-crystal to single-crystal phase transition at ca. 450 K. A combination of X-ray single-crystal and very-high flux powder neutron diffraction data confirmed that a proton does transfer from the acid to the base in the high-temperature form. Powder X-ray diffraction measurements demonstrated that the transition was reversible but that a significant kinetic energy barrier must be overcome to revert to the original structure. Computational modeling is consistent with these results. Modeling also revealed that, while the proton transfer event would be strongly discouraged in the gas phase, it occurs in the solid state due to the increase in charge state of the molecular ions and their arrangement inside the lattice. The color change is attributed to a narrowing of the squaric acid to bipyridine charge-transfer energy gap. Finally, evidence for the possible existence of two further phases at high pressure is also presented.

[Mn6] under Pressure: A Combined Crystallographic and Magnetic Study†

Folding under pressure: Crystallographic studies on a Mn6 single-molecule magnet under high pressure conditions show the drastic structural changes of the magnetic core (see picture, Mn purple, O red, N blue), which impact on the magnetic properties of ferromagnetic exchange between the metal atoms will be in booster weaker, and under extremely high pressure, a transition to antiferromagnetic behavior.

A Computational and Experimental Approach Linking Disorder, High-Pressure Behavior, and Mechanical Properties in UiO Frameworks

Abstract Whilst many metal–organic frameworks possess the chemical stability needed to be used as functional materials, they often lack the physical strength required for industrial applications. Herein, we have investigated the mechanical properties of two UiO‐topology Zr‐MOFs, the planar UiO‐67 ([Zr6O4(OH)4(bpdc)6], bpdc: 4,4′‐biphenyl dicarboxylate) and UiO‐abdc ([Zr6O4(OH)4(abdc)6], abdc: 4,4′‐azobenzene dicarboxylate) by single‐crystal nanoindentation, high‐pressure X‐ray diffraction, density functional theory calculations, and first‐principles molecular dynamics. On increasing pressure, both UiO‐67 and UiO‐abdc were found to be incompressible when filled with methanol molecules within a diamond anvil cell. Stabilization in both cases is attributed to dynamical linker disorder. The diazo‐linker of UiO‐abdc possesses local site disorder, which, in conjunction with its longer nature, also decreases the capacity of the framework to compress and stabilizes it against direct compression, compared to UiO‐67, characterized by a large elastic modulus. The use of non‐linear linkers in the synthesis of UiO‐MOFs therefore creates MOFs that have more rigid mechanical properties over a larger pressure range.

Pressure-induced Jahn–Teller switching in a Mn12 nanomagnet

Pressure-induced switching of a fast-relaxing single-molecule magnet to a slow-relaxing isomer is observed for the first time by using a combination of high pressure single-crystal X-ray diffraction and high pressure magnetic measurements.

Amino acids as highly efficient modulators for single crystals of zirconium and hafnium metal–organic frameworks

The synthesis of zirconium and hafnium metal–organic frameworks (MOFs) often relies on coordination modulation – the addition of competing monotopic modulators to reaction mixtures – to reproducibly generate highly crystalline material. Typically, large excesses of monocarboxylic acids such as formic, acetic and benzoic acid are applied, but access to diffraction quality single crystals, particularly of UiO-66 topology MOFs, remains troublesome. Herein, we show that amino acids, in particular L-proline, are highly efficient modulators of Zr and Hf MOFs of the UiO-66 series, with as little as four equivalents affording access to large, diffraction quality single crystals that are free of defects. Five crystal structures are reported, including MOFs which previously could not be characterised in this manner, with molecular dynamics simulations utilised to understand dynamic disorder. Additionally, a series of MOFs are characterised in depth, allowing a comparison of the thermal stabilities and porosities for Zr and Hf analogues. We also show that the protocol can be extended to microwave synthesis, and that modulating ability varies dramatically across a series of amino acids. Access to single crystals has facilitated our own in depth study of the mechanical properties of these MOFs, and we expect that our protocols will enable the discovery of new Zr and Hf MOFs as well as offer new insights into their materials properties.