Experimental and computational studies of two new mono- and dinuclear iridium complexes containing a Buchwald biphenyl phosphine ligand

The reaction of [(η⁴-1,5-C₈H₁₂)₂Ir₂(μ-Cl)₂] with 2-di-t-butylphosphino-2′-methylbiphenyl (t-Bu₂Pbiph^Me) in the presence of AgBF₄ afforded the dichlorido-bridged Ir–Ag complex [(η⁴-1,5-C₈H₁₂)Ir(μ-Cl)₂Ag(t-Bu₂Pbiph^Me)] (1) which was fully characterized by a single crystal X-ray diffraction study. Sequential treatment of the diiridium precursor first with the silver salt and then with the phosphine yielded cyclometalated [(η⁴-1,5-C₈H₁₂)Ir(t-Bu₂Pbiph^Me–H⁺)] (2). Detailed DFT calculations gave evidence that the phosphine ligand of 2 forms a strained four-membered iridaheterocycle through orthometalation rather than a sterically congested six-membered chelate structure through C–H activation on the remote phenyl ring. The phosphonium salt [t-Bu₂P(H)biph^Me]BF₄ was isolated as a by-product of the preparations of 1 and 2; its crystal structure was determined.     

Experimental studies on continuous hypothermic liver perfusion with a synthetic solution containing gelatin polypeptides (Haemaccel)

A rat liver model has been developed for studying preservation by continuous hypothermic perfusion. Perfusion for 5 and 24 hr with a defined solution containing Haemaccel as colloid at a temperature of 5–7 °C was found to result in good preservation of the metabolic activity of the livers as assessed by the ability of the tissue to synthesize urea and take up galactose. In common with other continuous perfusion methods, there was increasing evidence of cell damage as perfusion progressed, and there was an associated depletion of cellular K⁺ and an increase in tissue water content. There was a considerable increase in vascular resistance, as indicated by a fall in flow rate at a constant pressure in the later stages of perfusion, similar to that which has been reported in other liver preservation experiments using plasma derivatives or Dextran. Further studies are envisaged to attempt to analyze, in a controlled fashion, the nature of the damage incurred by the liver during storage and the requirements for maintenance of a viable graft at hypothermia.     

Conformational studies on beta-bend containing a cis peptide unit.

Conformational studies have been carried out on the X-cis-Pro tripeptide system (a system of three linked peptide units, in the trans-cis-trans configuration) using energy minimization techniques. For X, residues Gly, L-Ala, D-Ala and L-Pro have been used. The energy minima have been classified into different groups based upon the conformational similarity. There are 15, 20, 18 and 6 minima that are possible for the four cases respectively and these fall into 11 different groups. A study of these minima shows that, (i) some minima contain hydrogen bonds--either 4-->1 or 1-->2 type, (ii) the low energy minima qualify themselves as bend conformations, (iii) cis' and trans' conformations are possible for the prolyl residue as also the C gamma-endo and C gamma-exo puckerings, and (iv) for Pro-cis-Pro, cis' at the first prolyl residue is ruled out, due to the high energy. The available crystal structure data on proteins and peptides, containing cis-Pro segment have been examined with a view to find the minima that occur in solid state. The data from protein show that they fall under two groups. The conformation at X in X-cis-Pro is near extended when it is a non-glycyl residue. In both peptides and proteins there exists a preference for trans' conformation at prolyl residue over cis' when X is a non-glycyl residue. The minima obtained can be useful in modelling studies.     

Physico-chemical studies of a DNA triplex containing a new ferrocenemethyl-thymidine residue in the third strand

The stability of a 16-mer DNA triple helix containing a 3-N(ferrocenemethyl)-thymidine residue in the third strand has been investigated in comparison with the unmodified triplex of the same sequence. A complete physico-chemical characterization of the two triple helices on changing the pH by means of calorimetry, circular dichroism and molecular modeling is therefore reported. The thermodynamic parameters were obtained in the pH range 5.5-7.2 by differential scanning calorimetry (DSC). For both triplexes the T(m) and Delta H degrees (T(m)) values increase on decreasing the pH. In the pH range 7.2-6.0 the triplex containing the ferrocenemethyl nucleoside is less stable than the unmodified one, whereas the modified triplex becomes more stable at pH 5.5. Such difference in stability at each pH value is overwhelmingly enthalpic in origin. CD spectra show conformational changes on decreasing the pH for both the triplexes. By spectroscopic pH titration the apparent pK(a) values of the cytosines in the two triplexes could be estimated, with the cytosines in the TFO containing the ferrocenemethyl residue having lower apparent pK(a) values. These results are consistent with the calorimetric data, showing a decrease of the thermodynamic parameters in the pH range 7.2-6.0 and an increase at pH 5.5 for the ferrocenylated triplex with respect to the unmodified one. The thermodynamic and spectroscopic data are also discussed in relation to molecular models.     

The safety of a new chemical typhoid preparation containing a complex of Vi and K antigens in tests of its acute and chronic toxicity]

Acute and chronic toxicity of a new chemical typhoid preparation containing the complex of surface Vi- and K-antigens has been studied. The study has revealed that the preparation, when introduced subcutaneously and intravenously in immunizing doses in a single injection or in multiple injections, produces no toxic effect on the organs and tissues of experimental animals. In experiments of chronic toxicity the microscopic study has shown pronounced hyperplasia of the lymphoid system with enhanced macrophage reaction in the spleen, thymus, mesenteric lymph nodes and Peyer's patches in the small intestine.     

Experimental studies on toxicity of zinc to a freshwater teleost,rasbora daniconius (Hamilton)

Rasbora daniconius (Ham.) were exposed to zinc sulphate upto 15 days under static bioassay test conditions with renewal of the test solutions every 24 hours. Simultaneously control fish were also kept in water without zinc. The 96 and 240 hr LC₅₀ values were 38.1 and 33.3 PPm of zinc respectively. A reduced mortality rate was observed after 96 hr and LC₅₀ approached a constant value at 240 hr of exposure to the toxicant. Fish showed abnormal behaviour, deposition of mucus and appearance of haemorrhage on the body in case of higher concentrations of zinc, before death. The reported LC₅₀ values in the present study were comparatively higher than those reported by earlier investigators.See offprint requests to: Dr. V. K. Rajbanshi, Department of Limnology and Fisheries, University of Udaipur, Udaipur-313001, India.     

NMR studies of a DNA containing 8-hydroxydeoxyguanosine.

The effects of hydroxylation at the C8 of a deoxyguanosine residue in DNA were studied by NMR analysis of a self-complementary dodecanucleotide, d(C1-G2-C3-oh8G4-A5-A6-T7-T8-C9-G10-C11-G12), which has an 8-hydroxy-2'-deoxyguanosine (oh8dG) residue at the 4th position. NMR data indicate that the 8-hydroxyguanine (oh8G) base takes a 6,8-diketo tautomeric form and is base-paired to C with Watson-Crick type hydrogen bonds in a B-form structure. The thermal stability of the duplex is reduced, but the overall structure is much the same as that of the unmodified d(CGCGAATTCGCG) duplex. The structural changes caused by 8-hydroxylation of the deoxyguanosine, if any, are localized near the modification site.     

Phenacetin and the liver. The influence of phenacetin in acute and chronic doses on membrane-bound mitochondrial enzymes in the rat.

Following the administration of phenacetin in single and in multiple high doses, enzymes bound to the inner mitochondrial membrane of the liver were determined. Acute doses of phenacetin (75% of oral LD50) failed to produce any effect. The chronic administration of phenacetin provoked a small but statistically significant decrease in the TD-trnashydrogenase activity. This observation indicates that liver damage may occur in patients with phenacetin abuse.