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Biomedical subjects

Andrew Houlton

Publications and source records attributed to Andrew Houlton.

8 recordsLinked to original sources
PubMed2007

Synthesis, manipulation and conductivity of supramolecular polymer nanowires.

The synthesis of supramolecular conducting nanowires can be achieved by using DNA and pyrrole. Oxidation of pyrrole in DNA-containing solutions yields a material that contains both the cationic polypyrrole (PPy) and the anionic DNA polymers. Intimate interaction of the two polymer chains in the self-assembled nanowires is indicated by FTIR spectroscopy. AFM imaging shows individual nanowires to be continuous, approximately 5 nm high and conformationally flexible. This feature allows them to be aligned by molecular combing in a similar manner to bare DNA and provides a convenient method for fabricating a simple electrical device by stretching DNA/PPy strands across an electrode gap. Current-voltage measurements confirm that the nanowires are conducting, with values typical for a polypyrrole-based material. In contrast to polymerisation of pyrrole on a DNA template in bulk solution, attempts to form similar wires by polymerisation at surface-immobilised DNA do not give a continuous coverage; instead, a beads-on-a-string appearance is observed suggesting that immobilisation inhibits the assembly process.

DNA↗
PubMed2006

Multiple metal binding to 6-oxopurine nucleobases as a source of deprotonation. The role of metal ions at N7 and N3.

Simultaneous metal coordination to N7 (Pt(II)) and N3 (Pd(II)) of N9-blocked guanine leads to a 10(4) fold acidification of the guanine-N(1)H position and hence to a virtual complete deprotonation of the N(1)H position at neutral pH. The chelate-tethered nucleobase ethylenediamine-N9-ethylguanine was employed and relevant acid-base equilibria were studied by pD dependent 1H NMR spectroscopy. CH2 resonances of the tether were assigned on the basis of NOESY and COSY experiments. Our findings suggest a plausible method of formation of a previously reported trinuclear Pt(II) complex of 9-ethylguanine with metals coordinated to N1, N3 and N7. According to this, a sequence with the first metal binding to N7, the second one binding to N3, and only the third one binding to N1 with deprotonation of this site is proposed.

Binding Sites↗
PubMed2005

Mechanism of the hydrosilylation reaction of alkenes at porous silicon: experimental and computational deuterium labeling studies.

The mechanism of the formation of Si-C bonded monolayers on silicon by reaction of 1-alkenes with hydrogen-terminated porous silicon surfaces has been studied by both experimental and computational means. We propose that monolayer formation occurs via the same radical chain process as at single-crystal surfaces: a silyl radical attacks the 1-alkene to form both the Si-C bond and a radical center on the beta-carbon atom. This carbon radical may then abstract a hydrogen atom from a neighboring Si-H bond to propagate the chain. Highly deuterated porous silicon and FTIR spectroscopy were used to provide evidence for this mechanism by identifying the IR bands associated with the C-D bond formed in the proposed propagation step. Deuterated porous silicon surfaces formed by galvanostatic etching in 48% DF/D2O:EtOD (1:1) electrolytes showed a 30% greater density of Si-D sites on the surface than Si-H sites on hydrogen-terminated porous silicon surfaces prepared in the equivalent H-electrolyte. The thermal reaction of undec-1-ene and the Lewis acid catalyzed reaction of styrene on a deuterated surface both resulted in alkylated surfaces with the same C-C and C-H vibrational features as formed in the corresponding reactions at a hydrogen-terminated surface. However, a broad band around 2100 cm(-1) was observed upon alkylating the deuterated surfaces. Ab initio and density functional theory calculations on small molecule models showed that the integrated absorbance of this band was comparable to the intensity expected for the C-D stretches predicted by the chain mechanism. The calculations also indicate that there is substantial interaction between the hydrogen atoms on the beta-carbons and the hydrogen atoms on the Si(111)-H surface. These broad 2100 cm(-1) features are therefore assigned to C-D bands arising from the involvement of surface D atoms in the hydrosilylation reactions, while the line broadening can be explained partly by interaction with neighboring surface atoms/groups.

Journal Article↗
PubMed2004

Ferrocenyl-modified DNA: synthesis, characterization and integration with semiconductor electrodes.

The ferrocenyl-nucleoside, 5-ethynylferrocenyl-2'-deoxycytidine (1) has been prepared by Pd-catalyzed cross-coupling between ethynylferrocene and 5-iodo-2'-deoxycytidine and incorporated into oligonucleotides by using automated solid-phase synthesis at both silica supports (CPG) and modified single-crystal silicon electrodes. Analysis of DNA oligonucleotides prepared and cleaved from conventional solid supports confirms that the ferrocenyl-nucleoside remains intact during synthesis and deprotection and that the resulting strands may be oxidised and reduced in a chemically reversible manner. Melting curve data show that the ferrocenyl-modified oligonucleotides form duplex structures with native complementary strands. The redox potential of fully solvated ferrocenyl 12-mers, 350 mV versus SCE, was shifted by +40 mV to a more positive potential upon treatment with the complement contrary to the anticipated negative shift based on a simple electrostatic basis. Automated solid-phase methods were also used to synthesise 12-mer ferrocenyl-containing oligonucleotides directly at chemically modified silicon <111> electrodes. Hybridisation to the surface-bound ferrocenyl-DNA caused a shift in the reduction potential of +34 mV to more positive values, indicating that, even when a ferrocenyl nucleoside is contained in a film, the increased density of anions from the phosphate backbone of the complement is still dominated by other factors, for example, the hydrophobic environment of the ferrocene moiety in the duplex or changes in the ferrocene-phosphate distances. The reduction potential is shifted >100 mV after hybridisation when the aqueous electrolyte is replaced by THF/LiClO(4), a solvent of much lower dielectric constant; this is consistent with an explanation based on conformation-induced changes in ferrocene-phosphate distances.

Cytidine↗
PubMed2003

Minor groove site coordination of adenine by platinum group metal ions: effects on basicity, base pairing, and electronic structure.

Dithioether- or diamine-tethered adenine derivatives react with Pt(II), Pd(II), and Rh(III) ions to give N3-coordinated complexes of the types [MCl(SSN)](+) (M = Pt or Pd), [RhCl(3)(SSN)], or [RhCl(3)(NNN)] (where SSN = 1-(N9-adenine)-3,6-dithia-heptane or 1-(N9-adenine)-4,7-dithia-octane; NNN = ethylenediamine-N,9-ethyladenine). Single-crystal X-ray analysis confirms the nature of the metal-nucleobase interaction and highlights a conserved intermolecular hydrogen-bonding motif for all the complexes, irrespective of the metal-ion geometry. Coordination significantly reduces the basicity of the adeninyl group, as indicated by a pK(a) value of -0.16 for [PtCl(N3-1-(N9-adenine)-3,6-dithia-heptane)]BF(4), compared to a pK(a) value of 4.2 for 9-ethyladenine. The site of proton binding, N1 or N7, could not be unambiguously assigned from the (1)H NMR data, because of the similar effect on the chemical shifts of the H2 and H8 protons. Density functional calculations at the BP-LACVP level suggest N1 as the site of protonation for this type of complex. This is in contrast to the N7-protonation reported for [Pt(dien)(N3-6,6',9-trimethyladenine)](2+), as reported elsewhere (Meiser et al., Chem.-Eur. J. 1997, 3, 388). However, further electronic structure calculations in the gas phase reveal that the preferred site for protonation for N3-bound complexes is conformationally dependent. N3 coordination was also found to reduce the extent of base pairing between adenine and thymine in dimethylsulfoxide for the self-complementary complex [PtCl(L3)](+) (L3 = 1-(N9-adenine)-3,6-dithia-9-(N1-thymine)nonane), compared to that for the uncomplexed ligand.

Adenine↗
PubMed2002

Metallocene-DNA: synthesis, molecular and electronic structure and DNA incorporation of C5-ferrocenylthymidine derivatives.

Ferrocenylthymidine derivatives have been prepared by Pd-catalysed cross-coupling between ethynylferrocene or vinylferrocene and 5-iodo-2'-deoxyuridine. In the latter case a mixture of trans (2a) and gem (2b) isomers was obtained. The cis-vinylferrocenyl (2c), and ethylferrocenyl (3) derivatives were obtained by catalytic hydrogenation of ethynylferrocenyl-dT (1a), and 2c respectively. Single-crystal X-ray data for 1a, the ferrocenyl-2'furano-pyrimidone 1b, and 2a show that the nucleobase is essentially co-planar with the substituted Cp ring of the metallocene. The selective reduction of the linkage between the ferrocenyl and thymidine moieties, from -C identical to C- to -CH2CH2-, causes a shift in the reduction potential of -124 mV. DFT calculations for the one-electron oxidised species indicate that the diminished conjugation reduces the spin transfer onto the bridging C2 group, but has less effect on the extent transferred to the nucleobase from the ferrocenyl group. Compound 1a was incorporated site-specifically into DNA oligonucleotides by using automated solid-phase methods. However, some interconversion of 1a-->1b occurs, even under rapid mild conditions of deprotection.

Base Pairing↗