We report the effects induced by near-infrared apoferritin-PbS (AFt-PbS) nanocomposites on cell cycle progression in non-tumorigenic and cancerous human cells. By using flow cytometry and Annexin V assay, we show that the cell cycle of non-tumorigenic cells is not altered by exposure to AFt-PbS nanoparticles at concentrations up to 1 mg mL−1. In contrast, exposure of human-derived breast cancer cell lines to AFt-PbS at concentrations > 0.2 mg mL−1 triggers apoptotic cell death. The selective death of cancerous cells and the near-infrared fluorescence properties of AFt-PbS could be exploited in both nanomedicine and in vivo imaging studies.

Hydrophobic ion-pairing (HIP) with the fluorinated surfactant KDP 4606 (KDP) was used to extract the protein α-chymotrypsin (CMT) into perfluoromethylcyclohexane (PFMC). The diameter of the solubilised CMT-KDP complexes formed in PFMC was determined by dynamic light scattering (DLS) to be 25 nm which suggested the formation of a protein aggregate containing ∼100 protein molecules surrounded by KDP 4606 surfactant molecules per particle. The catalytic activity of the protease CMT either solubilised by HIP or as the suspended native enzyme has been investigated in both a fluorous biphasic system (FBS) and a supercritical carbon dioxide (scCO2) batch reactor. Transesterification of N-acetyl-L-phenylalanine ethyl ester (APEE) with n-butanol or rac-2-butanol was catalysed by the protease in the FBS hexane-PFMC or scCO2 at 40 °C. Under comparable conditions, the amount of transesterification of the solubilised protease–surfactant (CMT-KDP) complex in PFMC (6–10%) was shown to be significantly higher than that of the suspended protease (1–3%) in either hexane–PFMC or scCO2. This suggested the formation of a catalytically active CMT-KDP aggregate in PFMC. The CMT-KDP complex which is retained in the fluorous phase on cooling the solution was successfully reused over four cycles with no loss of activity.

The synthesis of 1,4-anhydro-β-D-galactopyranose (1,5-anhydro-α-D-galactofuranose), a proposed intermediate in the ring contraction isomerisation catalyzed by UDP-galactopyranose mutase, together with its [2.2.2] bicyclic methylene homologue, synthesised as a possible competitive inhibitor or alternative substrate, are reported. Neither compound was found to be an inhibitor or substrate for UDP-galactopyranose mutase from Klebsiella pneumoniae.

Frederic Stanley Kipping FRS is regarded as one of the founding fathers of silicon chemistry. In 57 research papers published between 1899 and 1944 he reported the first use of Grignard reagents to make alkylsilanes and arylsilanes and the prepartion of silicone oligomers and polymers. He coined the term ‘silicone’ in relation to these materials in 1904. His research formed the foundation for James Franklyn Hyde’s development of the first silicon based insulation materials at Corning Glass Works and then Dow Corning Corp., as well as inspiring Eugene G. Rochow’s work at General Electric Company in the development of the ‘direct method’ of silicone synthesis using silicon hydrides. Kipping was the first Sir Jesse Boot Professor of Chemistry at Nottingham University College and was married to Lily Holland whose sisters, Mina and Kathleen were married to two other prominent early 20th century British Chemists, William H. Perkin Jr. FRS and Arthur Lapworth FRS. This paper provides an insight into Professor Kipping’s life, personality and career.

The kinetic resolution (KR) and dynamic kinetic resolution (DKR) of racemic 1-phenylethanol with the acyl donor vinyl acetate catalysed by Pseudomonas cepacia lipase ATCC 21808 (PCL) (this has recently been reclassified as Burholderia cepacialipase), either as the suspended native protein (PCL) or immobilised on ceramic particles (commercial lipase Amano PS CI) has been examined, as batch reactions, in supercritical carbon dioxide (scCO2). The yields and enantioselectivities achieved in these reactions were comparable to experiments conducted in hexane. The immobilised lipase PS CI displayed excellent yields (48–49%) and enantioselectivities (98–99%) to give (R)-phenylethyl acetate after 2.5 hours reaction at 40 °C in scCO2. The acylated product was obtained in higher yield in scCO2 compared to the reaction carried out in hexane (yield 30–35%; ee 98–99%) under comparable conditions. Unlike PCL, the immobilised lipase PS CI could then be successfully reused with no loss of activity or selectivity observed over four reaction cycles. Combining lipase PS CI with a chemical catalyst (either the metal catalyst [Ru(p-cymene)Cl2]2 or the acid catalyst Nafion SAC 13) to catalyse the racemisation of the unreacted alcohol caused an increase in the yield of the (R)-acyl phenylethanol product to 70 and 85%, respectively, in scCO2 indicating a viable dynamic kinetic resolution system had been established. The enantioselectivities of the products in these reactions were slightly higher in scCO2 (96% Ru-catalyst; 85% Nafion) compared to those observed in hexane (91%; 81%). The lower enantioselectivity with the acidic Nafion SAC 13 catalyses indicates that some non-enzymic acid catalysed esterification was occurring.

Two new and complementary synthetic strategies for 5′-N-chloroethylamino-5′-deoxyadenosines are presented. Additionally, the reaction kinetics of their conversion into aziridines under typical enzyme assay conditions is reported using time-resolved NMR spectroscopy. A stable photocaged derivative of 5′-N-chloroethylamino-5′-deoxyadenosine has also been synthesized, and its stability and activation in aqueous solution at physiological pH have been examined.

We have engineered a variant of the β-clam shell protein ILBP which lacks the α-helical motif that caps the central binding cavity; the mutant protein is sufficiently destabilised that it is unfolded under physiological conditions, however, it unexpectedly binds its natural bile acid substrates with high affinity forming a native-like β-sheet rich structure and demonstrating strong thermodynamic coupling between ligand binding and protein folding.

Lysostaphin (EC. 3.4.24.75) is a protein secreted by Staphylococcus simulans biovar staphylolyticus and has been shown to be active against methicillin resistant S. aureus (MRSA). The design and synthesis of three internally quenched substrates for lysostaphin based on the peptidoglycan crossbridges of S. aureus, and their use in fluorescence resonance energy transfer (FRET) assays is reported. These substrates enabled the gathering of information about the endopeptidase activity of lysostaphin and the effect that mutations have on its enzymatic ability. Significant problems with the inner filter effect and substrate aggregation were encountered; their minimisation and the subsequent estimation of the kinetic parameters for the interaction of lysostaphin with the substrates is described, as well as a comparison of substrates incorporating two FRET pairs: Abz–EDDnp and DABCYL–EDANS. In addition to this, the points of cleavage caused by lysostaphin in Abz-pentaglycine-EDDnp have been determined by HPLC and mass spectrometry analysis to be between glycines 2 and 3 (∼60%) and glycines 3 and 4 (∼40%).

Two iminosugars have been designed and synthesized as potential inhibitors of UDP-Galf transferase, an enzyme involved in Mycobacterium tuberculosis cell wall biosynthesis. The design is based on a proposed model of the transition state for the transferase reaction. One of the two racemic compounds is the first reported inhibitor of the target enzyme from M. smegmatis.

The retroracemisation procedure developed by Belokon and coworkers has been re-examined using a variety of new (S)-2-[(N-alkylprolyl)amino]benzophenones chiral auxiliaries. It has been found that (S)-2-[(N-benzylprolyl)amino] and (S)-2-[(N-1-(naphthalenyl-1-methyl)prolyl)amino] benzophenones ((S)-BPB and (S)-NPB) when used in conjunction with Ni(NO3)2 · 6H2O and a racemic α-amino acid preferentially form a single diastereoisomer in the presence of a mild base such as sodium methoxide. Decomposition of this complex under acidic conditions leads to the isolation of the (S)-amino acid in good yield, and in 55 to 99% e.e. The retroracemisation abilities of a polymer supported form of the (S)-BPB ligand have also been investigated and preliminary results for this are presented here.Graphic

The intracellular ileal lipid binding proteins (ILBPs) are involved in the transport and enterohepatic circulation of bile acids. ILBPs from different species show high sequence and structural homology and have been shown to bind multiple bile acid ligands with differing degrees of selectivity and positive co-operativity. Human ILBP binds bile acid derivatives in a well-characterised 2:1 ligand:protein complex, however, we show that the highly homologous rabbit ILBP (82% sequence identity) with seven conservative substitutions preferentially binds multiple conjugated deoxycholate ligands in a novel 3:1 binding mode essentially within the same β-clam shell structure. We have extended these studies to investigate the role of the α-helical capping motif (residues 9–35) in controlling the dimensions of the binding cavity and ligand uptake. Substituting the α-helical motif (residues 9–35) with a short Gly-Gly-Ser-Gly linker dramatically affects the protein stability such that under physiological conditions the mutant (Δα–ILBP) is highly disordered. However, we show that the inability of the mutant to adopt a stable three-dimensional structure under these conditions is no barrier to binding ligands with near-native affinity. These structural modifications not only demonstrate the possibility of strong coupling between ligand binding and protein folding, but result in changes in bile acid selectivity and binding stoichiometry, which we characterise in detail using isothermal calorimetry and mass spectrometry.

The synthesis of 1,4-anhydro-β-D-galactopyranose (1,5-anhydro-α-D-galactofuranose), a proposed intermediate in the ring contraction isomerisation catalyzed by UDP-galactopyranose mutase, together with its [2.2.2] bicyclic methylene homologue, synthesised as a possible competitive inhibitor or alternative substrate, are reported. Neither compound was found to be an inhibitor or substrate for UDP-galactopyranose mutase from Klebsiella pneumoniae.