[1H,15N] N.M.R. Kinetic Studies of Reactions of cis- and trans-[PtCl2(15NH3)(c-C6H1115NH2)] with Guanosine 5'-Monophosphate

cis-[PtCl2(15NH3)(c-C6H11NH2)] is an active metabolite of the oral platinum(IV) anticancer drug cis,trans,cis-[PtCl2(CH3CO2)2(NH2)(c-C6H11NH2)]. Since it is likely that guanine bases on DNA are targets for this drug, we have analysed the kinetics of reaction of this platinum(II) metabolite with guanosine 5′-monophosphate (5′-GMP) at 310 K, pH 7, using [1H, 15N] n.m.r. methods. Reactions of the trans isomer are reported for comparison. The reactions proceed via aquated intermediates, and, for the cis isomer, the rates of aquation and substitution of H2O by 5′-GMP are 2-5 times faster trans to the amine ligand (c-C6H11NH2) compared to trans to NH3 for both the first and second steps. For the trans complex, the first aquation step is c. 3 times faster than for the cis complex, as expected from the higher trans influence of Cl¯, whereas the rate of the second aquation step (trans to N7 of 5′-GMP) is comparable to that trans to NH3. These findings have implications for the courses of reactions with DNA.

[Book review] Barry Mazur, Imagining Numbers: (Particularly the Square Root of Minus Fifteen)

Tony Mann provides a review of the book: Barry Mazur, Imagining Numbers: (Particularly the Square Root of Minus Fifteen), London: Allen Lane, 2003, ISBN: 0713996307

Numerical optimisation techniques applied to evacuation analysis

A common problem faced by fire safety engineers in the field of evacuation analysis concerns the optimal design of an arbitrarily complex structure in order to minimise evacuation times. How does the engineer determine the best solution? In this study we introduce the concept of numerical optimisation techniques to address this problem. The study makes user of the buildingEXODUS evacuation model coupled with classical optimisation theory including Design of Experiments (DoE) and Response Surface Models (RSM). We demonstrate the technique using a relatively simple problem of determining the optimal location for a single exit in a square room.