Amide complexes of (diethylenetriamine)platinum(II)

The coordination of acetamide and formamide to dienPtII is described. Both O- and N-bonded amide complexes are stable and have been isolated. As oxygen donor ligands for dienPtII, the binding affinity of amides lies between water and the very weakly coordinating acetone. The O-bonded amide complexes [dienPtOC(R)NH2]2+ are the kinetically preferred isomers in acetone but they rearrange very slowly (t1/2 ∼ 30 h, 20°C) and intramolecularly to the thermodynamically more stable N-bonded amide complexes (K = [N]/[O] ∼ 30). This is the reverse of relative amide affinities for harder metal ions (e.g. (NH3)5M3+, M = Co(III), Cr(III), Ru(III)) despite comparable polarizing power for dienPtII. The N-bonded amide isomers exist in solution (acetone, DMSO, water) as the imidol, [dienPtNH=C(OH)R]2+, rather than the amide tautomer, [dienPtNH2COR]2+, whereas the opposite has been observed for N-bonded ureas. The N-bonded amides adopt only one of the two possible geometric isomers which could result from restricted rotation about the amide N=C bond, and they are appreciably acidic (pKa 3.8, 20°C, H2O, I = 0.1 M; R = Me). Complexes of both O- and N-bonded amides are unstable in coordinating solvents (f1/2 40 h, N-isomers; 20°C, H2O), but no decomposition of the amide ligands was detected during solvolysis (amide release) in either DMSO or water, nor was the Pt(II) susceptible to aerial oxidation as reported for mixtures of amides with cis-diammineplatinum(II). Coordination preferences of amides to "soft" versus "hard" metals are compared

Inhibition of HIV-1 proteinase by metal ions

1. 1. Certain metal ions have been identified as inhibitors (IC50 1-20 μM) of the aspartic proteinase of Human Immunodeficiency Virus Type 1 (HIV-PR). 2. 2. By contrast most simple metal ions do not inhibit this enzyme. 3. 3. Those that did inhibit have in common a high charge/size ratio or "hard" acidic nature, preferring to combine covalently with oxygen donor ligands. 4. 4. Some evidence from independent X-ray crystal structure determinations suggests that the metalloinhibitors identified here may bind in the active site of the enzyme via coordination to the carboxylate side chains of the essential active site residues Asp 25 and 125. 5. 5. Although the measured inhibition is only μM, very few enzyme-inhibitor interactions can be taking place and so more complex metalloinhibitors with ligands that can also bind to peptide side chains of the enzyme might be significantly more potent inhibitors of HIV-PR and of viral replication

Changing Landscapes of Singapore: Old Tensions, New Discoveries

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Critical care usage after major gastrointestinal and liver surgery: a prospective, multicentre observational study

Background Patient selection for critical care admission must balance patient safety with optimal resource allocation. This study aimed to determine the relationship between critical care admission, and postoperative mortality after abdominal surgery. Methods This prespecified secondary analysis of a multicentre, prospective, observational study included consecutive patients enrolled in the DISCOVER study from UK and Republic of Ireland undergoing major gastrointestinal and liver surgery between October and December 2014. The primary outcome was 30-day mortality. Multivariate logistic regression was used to explore associations between critical care admission (planned and unplanned) and mortality, and inter-centre variation in critical care admission after emergency laparotomy. Results Of 4529 patients included, 37.8% (n=1713) underwent planned critical care admissions from theatre. Some 3.1% (n=86/2816) admitted to ward-level care subsequently underwent unplanned critical care admission. Overall 30-day mortality was 2.9% (n=133/4519), and the risk-adjusted association between 30-day mortality and critical care admission was higher in unplanned [odds ratio (OR): 8.65, 95% confidence interval (CI): 3.51–19.97) than planned admissions (OR: 2.32, 95% CI: 1.43–3.85). Some 26.7% of patients (n=1210/4529) underwent emergency laparotomies. After adjustment, 49.3% (95% CI: 46.8–51.9%, P<0.001) were predicted to have planned critical care admissions, with 7% (n=10/145) of centres outside the 95% CI. Conclusions After risk adjustment, no 30-day survival benefit was identified for either planned or unplanned postoperative admissions to critical care within this cohort. This likely represents appropriate admission of the highest-risk patients. Planned admissions in selected, intermediate-risk patients may present a strategy to mitigate the risk of unplanned admission. Substantial inter-centre variation exists in planned critical care admissions after emergency laparotomies

Body mass index and complications following major gastrointestinal surgery: A prospective, international cohort study and meta-analysis

Aim Previous studies reported conflicting evidence on the effects of obesity on outcomes after gastrointestinal surgery. The aims of this study were to explore the relationship of obesity with major postoperative complications in an international cohort and to present a metaanalysis of all available prospective data. Methods This prospective, multicentre study included adults undergoing both elective and emergency gastrointestinal resection, reversal of stoma or formation of stoma. The primary end-point was 30-day major complications (Clavien–Dindo Grades III–V). A systematic search was undertaken for studies assessing the relationship between obesity and major complications after gastrointestinal surgery. Individual patient meta-analysis was used to analyse pooled results. Results This study included 2519 patients across 127 centres, of whom 560 (22.2%) were obese. Unadjusted major complication rates were lower in obese vs normal weight patients (13.0% vs 16.2%, respectively), but this did not reach statistical significance (P = 0.863) on multivariate analysis for patients having surgery for either malignant or benign conditions. Individual patient meta-analysis demonstrated that obese patients undergoing surgery formalignancy were at increased risk of major complications (OR 2.10, 95% CI 1.49–2.96, P < 0.001), whereas obese patients undergoing surgery for benign indications were at decreased risk (OR 0.59, 95% CI 0.46–0.75, P < 0.001) compared to normal weight patients. Conclusions In our international data, obesity was not found to be associated with major complications following gastrointestinal surgery. Meta-analysis of available prospective data made a novel finding of obesity being associated with different outcomes depending on whether patients were undergoing surgery for benign or malignant disease