Pure and Applied Chemistry Department

Developed and delivered a workshop entitled Developing a Social Media Plan for Graduate Job Searching as part of a Higher Education Academy (HEA) project led by Debbie Willison, University of Strathclyde to develop a toolkit of resources to support students to develop self marketing and personal awareness skills.

Developed and delivered a workshop entitled Developing Communicating your research through social media - Social media for researchers as part of the Becoming an Engaging Researcher module organised by the Rseearcher Development Programme, University of Strathclyde.

The isomerisation of readily available (Z)-4-(para-methoxybenzyloxy)-1-chloro-2-butene was achieved under mild conditions to afford the much less accessible E-diastereoisomer. This was an effective substrate in Sharpless asymmetric dihydroxylation (AD) reactions, delivering highly enantiomerically enriched fluorinated butene triol building blocks.

The dyes Nile Blue (C. I. Basic Blue 12) and Thionine (C. I. 52000) were examined in both ionic and neutral forms in different solvents using NMR and UV–visible spectroscopy to firmly establish the structures of the molecules and to assess the nature and extent of their aggregation. 1H and 13C NMR assignments and chemical shift data were used, together

The use of two-dimensional diffusion-edited total-correlation NMR spectroscopy (DETOCSY) to measure diffusion coefficients of molecules in biofluids is demonstrated. The method takes advantage of the increased peak dispersion in a two-dimensional spectrum and allows the measurement of diffusion coefficients of individual molecules in complex biofluid samples in a condition close to their natural state. The NMR spectra can be edited on the basis of diffusion coefficient, and hence, approximate molecular size and this provides a qualitative means of simplifying the spectra for assignment purposes. The use of two-dimensional DETOCSY NMR spectra increases the probability that the individual cross-peaks arise from single components and hence allows single-exponential fitting of the magnetic field gradient dependence of cross-peak volumes. Interpretation of the derived diffusion coefficients improves the NMR resonance assignment process in complex biofluid mixtures by giving additional information on the molecular size. The DETOCSY approach also provides information on small molecule-macromolecule interactions such as the binding of drugs or endogenous species to serum proteins such as albumin.

Organometallic ruthenium(II) arene anticancer complexes of the type [(η 6 -arene)Ru(II)(en)Cl ][PF 6 ] (en = ethylenediamine) specifically target guanine bases of DNA oligomers and form monofunctional adducts (Morris, R., et al. J. Med. Chem. 2001). We have determined the ...

Human albumin (studied here as the recombinant protein rHA), a copper-binding protein in blood plasma, is shown to reduce Cu(II) to Cu(I) in the presence of a Cu(I) chelator, bathocuproinedisulfonate (BD). This reaction was accelerated at low pH, when there was little binding of Cu(II) to rHA. The addition of a competitive metal ion, Ni(II), or an increase in the concentration of BD, enhanced the reduction of Cu(II) to Cu(I). It was concluded that the oxidant was the Cu(II) complex of BD, which is likely to bind strongly to albumin. The free thiol at Cys34 was ruled out as the sole reducing agent, since Cys34-blocked albumin also gave rise to Cu(I) in the presence of BD. Reactions with amino acids and peptides suggested that Tyr and possibly His side-chains are potential reductants. BD and its homologues are frequently used as Cu(I)-specific chelators in biological experiments, but the strong oxidant activity of [Cu(II)(BD)2]2- and its ability to bind to biological macromolecules should not be overlooked, and may artificially trigger/accelerate Cu(II) reduction.

The Ru(II) organometallic antitumor complex [(eta(6)-biphenyl)RuCl(en)][PF(6)] (1) reacts slowly with the amino acid L-cysteine (L-CysH(2)) in aqueous solution at 310 K. Reactions were followed over periods of up to 48 h using HPLC, electronic absorption spectroscopy, LC-ESI-MS, and 1D or 2D (1)H and (15)N NMR spectroscopy. Reactions at a 1 mM/2 mM (Ru/L-CysH(2)) ratio were multiphasic in acidic solutions (pH 5.1) and appeared to involve aquation as the first step. Initially, 1:1 adducts involving substitution of Cl by S-bound or O-bound L-CysH(2), [(eta(6)-biphenyl)Ru(S-L-CysH)(en)](+) (4a) and [(eta(6)-biphenyl)Ru(O-L-CysH(2))(en)](2+) (4b) formed, followed by the cystine adduct [(eta(6)-biphenyl)Ru(O-Cys(2)H(2))(en)](2+) (3), and two dinuclear complexes from which half or all of the chelated ethylenediamine had been displaced, [(eta(6)-biphenyl)Ru(H(2)O)(microS,N-L-Cys)Ru(eta(6)-biphenyl)(en)](2+) (5) containing one bridging cysteine, and [(eta(6)-biphenyl)Ru(O,N-L-Cys-S)(S-L-Cys-N)Ru(eta(6)-biphenyl)(H(2)O)] (6) containing two bridging cysteines. The unusual cluster species [(biphenyl)Ru](8) (7a) was also detected by MS and was more prevalent in reactions at higher L-CysH(2) concentrations. Complex 5 was the dominant product at pH 2-5, but overall, only ca. 50% of 1 reacted with L-CysH(2) in these conditions. The reaction between 1 and L-CysH(2) was suppressed in 50 mM triethylammonium acetate solution at pH > 5 or in 100 mM NaCl. Only 27% of complex 1 reacted with L-methionine (L-MetH) at an initial pH of 5.7 after 48 h at 310 K and gave rise to only one adduct [(eta(6)-biphenyl)Ru(S-L-MetH)(en)](2+) (8).

Esters of crotonic acid were brominated on a multigramme scale using a free radical procedure. A phase transfer catalysed fluorination transformed these species to the 4-fluorobut-2E-enoates reproducibly and at scale (48-53%, ca. 300 mmol). Asymmetric dihydroxylation reactions were then used to transform the butenoate, ultimately into all four diastereoisomers of a versatile fluorinated C4 building block at high enantiomeric-enrichment. The (DHQ)2AQN and (DHQD)2AQN ligands described by Sharpless were the most effective. The development and optimisation of a new and facile method for the determination of ee is also described; (19)F{(1)H} spectra recorded in d-chloroform/diisopropyl tartrate showed distinct baseline separated signals for different enantiomers.

We have investigated the recognition of nucleic acid derivatives by organometallic ruthenium(II) arene anticancer complexes of the type [(eta(6)-arene)Ru(II)(en)X] where en = ethylenediamine, arene = biphenyl (Bip), tetrahydroanthracene (THA), dihydroanthracene (DHA), p-cymene (Cym) or benzene (Ben), X = Cl(-) or H(2)O using (1)H, (31)P and (15)N ((15)N-en) NMR spectroscopy. For mononucleosides, [(eta(6)-Bip)Ru(en)](2+) binds only to N7 of guanosine, to N7 and N1 of inosine, and to N3 of thymidine. Binding to N3 of cytidine was weak, and almost no binding to adenosine was observed. The reactivity of the various binding sites of nucleobases toward Ru at neutral pH decreased in the order G(N7) > I(N7) > I(N1), T(N3) > C(N3) > A(N7), A(N1). Therefore, pseudo-octahedral diamino Ru(II) arene complexes are much more highly discriminatory between G and A bases than square-planar Pt(II) complexes. Such site-selectivity appears to be controlled by the en NH(2) groups, which H-bond with exocyclic oxygens but are nonbonding and repulsive toward exocyclic amino groups of the nucleobases. For reactions with mononucleotides, the same pattern of site selectivity was observed, but, in addition, significant amounts of the 5'-phosphate-bound species (40-60%) were present at equilibrium for 5'-TMP,…