Biomedical subjects
Publications and source records attributed to Roger Taylor.
Trifluoromethylation of [60]- and [70]fullerenes occurs across both 6:6- and 5:6-bonds giving unsymmetrical tetramethyl adducts having four contiguous CF3 groups; both fullerenes give bis adducts which do not involve 6:6-addition, and unsymmetrical hexa-adducts (with contiguous CF3 groups) are also obtained from [60]fullerene.
A range of tertiary carbanions XCH(CO2Et)2 of differing sizes have been reacted with C60F18 to assess the steric effect of X on the position of nucleophilic substitution. For X = CO2Et, NO2, P(O)(OMe)2, SO2CH2Ph, the all trans annulenes (trannulenes) were obtained as a result of extended S(N)2' (i.e. S(N)2'') substitution; in the case of the phosphorus compound, with reduced amounts of base (DBU) dephosphonylation of one or more P(O)(OMe)2 groups by hydrogen occurred. Trannulene formation did not occur for X = F, CN due to the smaller size of the nucleophile, and in the latter case substitution was shown to take place by an S(N)2' mechanism, resulting in the addend being adjacent to a fluorine addend. Trannulenes (X = CO2Et, Br, Cl) exhibited reversible one-electron reductions at potentials (-0.02 to -0.09 V) significantly more positive than for [60]fullerene. Trannulene (X = NO2) exhibited an irreversible one-electron reduction (0.08 V); the irreversibility may be associated with fluorine loss. Conformational isomerism at temperatures below 298 K was observed for all trannulene derivatives as a result of eclipsing addend-addend interactions. Minimum energy conformations with a rotational energy barrier of 12-15 kcal mol(-1) were observed when these interactions are calculated using molecular mechanics.
The reaction of C60F18 with phenol, 2-naphthol and quinol in the presence of ferric chloride leads to initial electrophilic substitution (aryldefluorination). This occurs at both ortho and para positions for phenol, at the ortho position for quinol, and at the relatively hindered but most reactive 1-position for 2-naphthol. It is followed, where sterically favourable, by HF loss either between the OH group and F (rendered adjacent as a result of a 1,3-shift) or to attack of the OH group at an adjacent double bond with loss of a beta-fluorine, giving benzofurano[2',3':10,26]hexadecafluoro[60]fullerene derivatives. The reaction is accompanied by some complete defluorination leading, in reaction with phenol and with 2-naphthol, to the formation of benzofurano[2',3':1,2][60]fullerene and naphtho[2,1:b]furano[d:1,2][60]-fullerene, respectively. The mechanism of base-catalysed reaction of phenols with C60Cl6 is re-evaluated.
Co-evaporation of solutions of C(60)F(18) and tetrathiafulvalene in toluene produces an unsymmetrical C(60)F(16):tetrathiafulvalene adduct through a unique six-electron cycloaddition involving displacement of two fluorine atoms by a terminal Cdbond;C double bond of the fulvalene. The adduct rearranges into two further adducts, one of which is characterised as a new type of fullerene derivative, a thiiranofullerene, formed by elimination of a thioketene moiety from the tetrathiafulvalene adduct. The initial addition also produces a bisadduct in which the addends comprise one tetrathiafulvalene molecule and one in which carbon disulfide has been eliminated. The latter adduct involves cycloaddition of an unsaturated aromatic dithiolactone moiety.
On standing in organic solvents containing traces of water, C3 and C1 isomers of C60F36 slowly convert to C1 isomers of C60F35OH. Both fluorofullerenols eliminate HF during EI mass spectrometry to give C60F34O epoxides, one fullerenol being much less stable than the other to the extent that the mass spectrum shows only the epoxide. Both C60F35OH isomers have C1 symmetry, one being identified by the remarkable linear relationship between chemical shifts in its 19F NMR spectrum and those in the spectrum of C1 C60F36; the spectrum of the other shows the pattern of C3 C60F36 rendered asymmetrical by the replacement of one F by OH. The reactions are facilitated by the presence of isolated double bonds, and provide the first proven examples of an SN2' reaction of a fullerene derivative. Our observation explains why only a limited number of fluorines are readily replaced in C60F36 and why C60F18 is by contrast much more resistant to hydrolysis. We have isolated also a pure isomer of C60F36O, which is shown to be an oxahomofullerene (ether) apparently derived from C1 C60F36, and an impure fraction comprising a fourth isomer of C60F36, a trifluoromethyl derivative of C60F36, a second isomer of C60F36O, and an unknown species of 1392 u.
In a first example of a trannulene-based donor-acceptor dyad visible light photoexcitation generates a long-lived (870 ns) charge-separated state.
The low density lipoprotein (LDL) receptor-related protein (LRP) is a multifunctional receptor involved in numerous biological processes relevant to vascular biology including lipoprotein metabolism. Several polymorphisms in the LRP gene have been described and in this study we examined their influence on coronary artery disease (CAD). We compared the frequencies of the exon 3 (C766T), exon 6 (C663T), exon 22 (C200T), and four rarer and more recently described polymorphisms in approximately 600 Caucasian subjects aged <50 years with angiographic CAD and approximately 700 similarly aged subjects without symptomatic CAD randomly selected from the community. We found the distribution of exon 22 C200T genotypes to differ significantly between the CAD (CC: 52%, CT: 39%, TT: 9%) and control subjects (CC: 43%, CT: 46%, TT: 11%, P=0.005), with the CC genotype conferring an odds ratio (OR) for CAD of 1.5 (95% CI: 1.2-1.8, P=0.001) despite a lack of significant influence on plasma cholesterol or triglyceride. The other LRP polymorphisms were less common. Two showed an association with CAD; for the exon 3 C766T polymorphism the TT genotype was significantly lower (1.0 vs. 2.7%; OR: 0.36; P=0.04) and, for the exon 6 C663T polymorphism, the heterozygote frequency was higher (6.2 vs. 3.4%; OR: 1.9; P=0.03) in CAD subjects. In conclusion, LRP gene polymorphisms, particularly the relatively common exon 22 C200T polymorphism, are a significant risk factor for premature CAD in Caucasians.
In a toluene/CDCl3 solution at room temperature, the C1 isomer of C60F36 rearranges into the C3 isomer over a period of four days, as a result of a unique 1,3-shift of fluorine; this rare example of addend migration across a fullerene cage surface is accelerated by air.
There is considerable disagreement over how hospital mortality rates should be measured. There are concerns that hospitals with a high number of geriatric beds and long-stay patients are bound to appear to do badly in terms of mortality rates. Analysis of death rates in English trusts shows mortality rates do vary for length of stay. After standardisation for age group and length of stay, the adjusted mortality rates show no bias against hospitals with more patients staying more than 28 days, or against hospitals with more geriatric beds.
From fluorination of [60]fullerene with MnF3/K2NiF6 at 480 degrees C we have isolated and characterized by both 19F NMR spectrum and single crystal X-ray analysis, a C1 isomer of C60F36; it has three planar delocalized aromatic rings, three short C=C bonds (due to compression from the adjacent fluorines), the longest FC-CF bond (1.684 A) yet found in a fluorofullerene, and its stability is predicted by calculations.
Tetrahedral C60F36 is shown by its single-crystal X-ray structure to be the most aromatic (and distorted) fullerene derivative, having four planar hexagons with almost equal bond lengths, the average of which (1.373 A) is the same as in C60F18; one exceptionally long FC-CF bond (1.665 A) corresponds to the similarly long bond in C60F18 (a motif of T C60F36) and is likely to be the site of oxygen insertion in C60F36O.
Electron transfer reduction of a highly electron-deficient fullerene, C60F18, to the defluorinated anion, C60F17- occurs efficiently by a relatively weak one-electron reductant, p-chloranil radical anion; the one-electron reduction potential of C60F18 is evaluated as 0.04 V (vs. SCE) by comparison of the rate constant for electron-transfer from 10,10'-dimethyl-9,9',10,10'-tetrahydro-9,9'-biacridine to C60F18 with those of other one-electron reductants.
We investigated the effect of an 8 week circuit training (CT) program, combining aerobic and resistance exercise, on indices of glycemic control, cardiorespiratory fitness, muscular strength and body composition in 16 subjects (age 52 +/- 2 years) with type 2 diabetes using a prospective randomised crossover protocol. Submaximal exercise heart rate and rate pressure product were significantly lower after training (P<0.05), whilst ventilatory threshold increased (11.8 +/- 0.7 vs 13.8 +/- 0.6 ml kg(-1)min(-1), P<0.001). Muscular strength also increased with training (403 +/- 30 to 456 +/- 31 kg, P<0.001), whilst skinfolds (148.7 +/- 11.5 vs 141.1 +/- 10.7 mm, P<0.05), % body fat (29.5 +/- 1.0 vs 28.7 +/- 1.1%, P<0.05) and waist:hip ratio (99.2 +/- 1.5 vs 97.9 +/- 1.4%, P<0.05) significantly decreased. Concurrently, peak oxygen uptake (P<0.05) and exercise test duration (P<0.001) increased following training, whilst glycated hemoglobin (P<0.05) and fasting blood glucose (P<0.05) decreased. CT is an effective method of training that improved functional capacity, lean body mass, strength and glycemic control in subjects with type 2 diabetes.
Tumour necrosis factor-alpha (TNF alpha) is a mediator of reactive oxygen species, which are implicated in endothelial dysfunction and atherosclerosis. Type II diabetes is associated with endothelial dysfunction and elevated circulating TNF alpha. We hypothesized that reducing serum levels of TNFalpha, using pentoxifylline, would improve endothelial function. Thirteen subjects [age 58+/-2 (S.E.M.) years] with Type II diabetes (disease duration 74+/-13 months) undertook a randomized, crossover study of 8 weeks pentoxifylline and 8 weeks placebo. Endothelium-dependent and-independent vasodilation in resistance arteries was assessed via bilateral forearm venous occlusion plethysmography during intra-brachial infusions of acetylcholine (ACh), sodium nitroprusside (SNP) and N(G)-monomethyl-L-arginine (L-NMMA). High-resolution ultrasound of the brachial artery in response to ischaemia was used to determine endothelium-dependent conduit vessel flow-mediated dilation (FMD), and endothelium-independent conduit function was assessed by sublingual administration of glyceryl trinitrate (GTN). Serum concentrations of TNF alpha were also determined. Pentoxifylline lowered serum TNF alpha from 4.1+/-0.7 to 2.9+/-0.6 pg x ml(-1) (P=0.001). Forearm blood flow (FBF) responses at each dose of ACh did not differ with treatment (P=0.4). Similarly, FBF responses to SNP (P=0.8) and L-NMMA (P=0.2) did not differ. There was also no significant difference in brachial artery diameter during FMD (P=0.2) or GTN administration (P=0.06). Despite lowering serum TNF alpha concentration, pentoxifylline at a dose of 400 mg three times a day for 8 weeks did not improve vascular function in either conduit or resistance vessels in this group of Type II diabetic subjects.
We examined vascular function in an inactive muscle bed, the forearm, during lower limb exercise and determined the contribution of endothelium-derived nitric oxide (NO) to the hyperemic response. Eight young males were randomized to participate in two studies, each consisting of two bouts of lower limb exercise, separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood flow (MFBF) were continuously recorded at baseline and during exercise using continuous high-resolution vascular ultrasound and Doppler flow velocity measurement. During one session, the brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase. The alternate session was performed to control for possible effects of repeated exercise. At 60, 100, and 160 W, L-NMMA significantly decreased both PFBF and MFBF compared with the saline infusion. These results suggest that systemic production of NO occurs during exercise in resting vessel beds, which do not feed metabolically active tissue. This finding provides a plausible explanation for the antiatherogenic benefits of exercise.
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