0113 343 3725
Clothworkers' Building South, Room 3.07
MChem PhD MRSC
Dr Hebden obtained a Masters’ degree in Chemistry before studying for a PhD in Chemistry both at University of Leeds. Subsequently he worked for a university spin-out company called DyeCat ltd specialising in in-situ coloration of sustainable polymers and catalysed dyeing.
Dr Hebden works in the Fibre and Fabric Functionalisation Research Group at the University of Leeds.
(2017) “Single step assembly of biomolecule-loaded sub-micron polysulfone fibers”, Textile Research Journal. 87.3: 340-350.
DOI: 10.1177/0040517516629148, Repository URL: http://eprints.whiterose.ac.uk/93121/
© 2016, © The Author(s) 2016. Enrichment of chemically resistant hydrophobic polymers with polar biomolecules is relevant to the production of fiber-based drug delivery devices and adsorptive filtration media, as well as fibers for selective molecular recognition of antibodies, enzymes and nucleic acids. Polysulfone (PSU) is an amorphous polymer possessing high-strength, rigidity and excellent thermal stability. The preparation of PSU spinning solutions requires lengthy dissolution times at elevated temperature that tends to degrade commixed polar biomolecules. Using the highly polar metabolite creatinine, as a model system, a variety of co-solvents was evaluated for electrospinning commixed solutions of PSU and creatinine at room temperature. The selection of solvent systems was informed by Hansen solubility parameters. A binary system of N, N-dimethylacetamide (DMAc):methanol (4:1) was not found to be a suitable solvent because of the need for elevated temperature (80℃) to facilitate dissolution, and a binary solvent system of N, N-dimethylformamide (DMF):dimethyl sulfoxide (DMSO) (3:2) resulted in nozzle blockage during spinning. A binary system of DMAc:DMSO (13:7) enabled preparation of PSU with creatinine at ambient temperature, and sub-micron fibers substantially free of beads were produced continuously via electrospinning, yielding fiber diameters in the range 470–870 nm. The presence of creatinine was confirmed by high performance liquid chromatography (HPLC), and fiber morphology was examined by scanning electron microscopy (SEM).
(2015) “Hypoxia-Sensitive Metal β-Ketoiminato Complexes Showing Induced Single-Strand DNA Breaks and Cancer Cell Death by Apoptosis”, Journal of Medicinal Chemistry. 58.12: 4940-4953.
DOI: 10.1021/acs.jmedchem.5b00455, Repository URL: http://eprints.whiterose.ac.uk/87261/
© 2015 American Chemical Society. A series of ruthenium and iridium complexes have been synthesized and characterized with 20 novel crystal structures discussed. The library of β-ketoiminato complexes has been shown to be active against MCF-7 (human breast carcinoma), HT-29 (human colon carcinoma), A2780 (human ovarian carcinoma), and A2780cis (cisplatin-resistant human ovarian carcinoma) cell lines, with selected complexes' being more than three times as active as cisplatin against the A2780cis cell line. Selected complexes were also tested against the noncancerous ARPE-19 (retinal pigment epithelial cells) cell line, in order to evaluate the complexes selectivity for cancer cells. Complexes have also been shown to be highly active under hypoxic conditions, with the activities of some complexes increasing with a decrease in O < inf > 2 < /inf > concentration. The enzyme thioredoxin reductase is overexpressed in cancer cells, and complexes reported herein have the advantage of inhibiting this enzyme, with IC < inf > 50 < /inf > values measured in the nanomolar range. The anticancer activity of these complexes was further investigated to determine whether activity is due to effects on cellular growth or cell survival. The complexes were found to induce significant levels of cancer cell death by apoptosis with levels induced correlating closely with activity in chemosensitivity studies. As a possible cause of cell death, the ability of the complexes to induce damage to cellular DNA was also assessed. The complexes failed to induce double-strand DNA breaks or DNA cross-linking but induced significant levels of single-strand DNA breaks, indicating a mechanism of action different from that of cisplatin.
Group IV metal complexes have previously shown promise as novel anticancer agents. Here, we discuss the mechanistic and cytotoxic nature of a series of group IV β-diketonate coordination complexes. Clear evidence that the ligands are exchangeable on the metal centre and that the β-diketonate ligands can act as potential drug delivery vehicles of the group IV metal ions was obtained. When evaluated for the cytotoxicity against human colon adenocarcinoma (HT-29) and human breast adenocarcinoma (MCF-7) cell lines, a general trend of decreasing potency down the group IV metals was observed. The most promising results obtained were for the hafnium complexes, with the tris diphenyl β-diketonate hafnium complex exhibiting IC50 values of 4.9 ± 0.9 μM and 3.2 ± 0.3 μM against HT-29 and MCF-7, respectively, which are comparable with the activity of cisplatin against the same cell lines. This tri β-diketonate hafnium complex is the first to show potent in vitro cytotoxic activity. The results reported show that ligand design has a significant effect on the cytotoxic potential of the complexes, and that these group IV complexes warrant further evaluation as novel metal-containing anticancer agents.
(2014) “Rhodium, iridium, and ruthenium half-sandwich picolinamide complexes as anticancer agents.”, Inorg Chem. 53.2: 727-736.
DOI: 10.1021/ic401529u, Repository URL: http://eprints.whiterose.ac.uk/126829/
Novel rhodium, iridium, and ruthenium half-sandwich complexes containing (N,N)-bound picolinamide ligands have been prepared for use as anticancer agents. The complexes show promising cytotoxicities, with the presence, position, and number of halides having a significant effect on the corresponding IC50 values. One ruthenium complex was found to be more cytotoxic than cisplatin on HT-29 and MCF-7 cells after 5 days and 1 h, respectively, and it remains active with MCF-7 cells even under hypoxic conditions, making it a promising candidate for in vivo studies.
(2010) “Studies in micelle-mediated Pd nucleation.”, Chem Commun (Camb). 46.36: 6663-6665.
Manipulation of metal atom nucleation and particle growth in solution is virtually unexplored, but highly sought after for the creation of functional materials and rational design of supramolecular structures. We therefore decided to explore this area through the self-assembly of block copolymer micelles and Pd atoms without using a chemical reduction reaction.
(2009) “Amide Linkage Isomerism As an Activity Switch for Organometallic Osmium and Ruthenium Anticancer Complexes”, J MED CHEM. 52.23: 7753-7764.