[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.

Simulation of ship evacuation and passenger circulation

This paper describes work carried out in the FIRE EXIT research project. FIRE EXIT aims to develop an Evacuation Simulator, capable of addressing issues of mustering, ship motions, fire and abandonment. In achieving these aims, FIRE EXIT took as its starting point the state-of-the-art in ship evacuation simulation (the maritimeEXODUS software), fire simulation (the SMARTFIRE software) and large-scale experimental facilities (the SHEBA facility). It then significantly enhanced these capabilities. A number of new technologies have been developed in achieving these objectives. The innovations include directly linking CFD fire simulation with evacuation and abandonment software and automatic data transfer from concept design software allowing rapid generation of ship simulation models. Software usability was augmented by a module for interpretation of evacuation software output. Enhancements to a ship evacuation testing rig have resulted in a unique facility, capable of providing passenger movement data for realistic evacuation scenarios and large scale tests have provided meaningful data for the evacuation simulation.