pKa values of aqua ligands of platinum (II) anticancer complexes: [1H, 15N] and 195Pt NMR Studies of cis- and trans- [PtCl2 (NH3) (Cyclohexylamine)]

Syntheses and NMR studies are reported of two 15N-labelled Pt(II) complexes of anticancer interest: cis-PtCl2(15NH3)(c-C6H1115NH2), a metabolite of the orally-active Pt(IV) complex cis,trans,cis-[PtCl2(acetate)2(c-C6H11NH2)(NH3), and trans-[PtCl2(15NH3)(c-C6H1115NH2), a reduction product of the active Pt(IV) complex trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2). For cis-[PtCl2(15NH3)(c-C6H1115NH2), hydrolysis was faster for the chloride ligand trans to cyclohexylamine, and the pKa values determined by [1H, 15N NMR spectroscopy for the two cis monoaqua isomers were the same (6.73). The trans monoaqua complex was a stronger acid with pKa of 5.4 (determined by 195Pt NMR). For the cis diaqua complex, pKa values of 5.68 and 7.68 were determined.

[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.

Research in statistical education — planning of an international survey

As announced in the November 2000 issue of MathStats&OR [1], one of the projects supported by the Maths, Stats & OR Network funds is an international survey of research into pedagogic issues in statistics and OR. I am taking the lead on this and report here on the progress that has been made during the first year. A paper giving some background to the project and describing initial thinking on how it might be implemented was presented at the 53rd session of the International Statistical Institute in Seoul, Korea, in August 2001 in a session on The future of statistics education research [2]. It sounded easy. I considered that I was something of an expert on surveys having lectured on the topic for many years and having helped students and others who were doing surveys, particularly with the design of their questionnaires. Surely all I had to do was to draft a few questions, send them electronically to colleagues in statistical education who would be only to happy to respond, and summarise their responses? I should have learnt from my experience of advising all those students who thought that doing a survey was easy and to whom I had to explain that their ideas were too ambitious. There are several inter-related stages in survey research and it is important to think about these before rushing into the collection of data. In the case of the survey in question, this planning stage revealed several challenges. Surveys are usually done for a purpose so even before planning how to do them, it is advisable to think about the final product and the dissemination of results. This is the route I followed.

Statistical analysis of extreme forest fires

Forest fires can cause extensive damage to natural resources and properties. They can also destroy wildlife habitat, affect the forest ecosystem and threaten human lives. In this paper extreme wildland fires are analysed using a point process model for extremes. The model based on a generalised Pareto distribution is used to model data on acres of wildland burnt by extreme fire in the US since 1825. A semi-parametric smoothing approach is adapted with maximum likelihood method to estimate model parameters.

Statistical investigations - drawing it all together

The author's approach to teaching an integrative unit to a small group of master’s level Applied Statistics students in 2000-2001 is described. Details of the various activities such as data analysis, reading and discussion of papers, and training in consultancy skills are given, as also are details of the assessment. The students’ and lecturer’s views of the unit are discussed.

The Royal Statistical Society and statistical education

This paper describes the role of the Royal Statistical Society in shaping statistical education within the UK and further afield. Until 2001 the Society had four agencies concerned with education at all levels. The work of these is discussed and recent new arrangements are outlined. The Society’s efforts to disseminate good practice through organising meetings and running a network of Associate Schools and College are explored in some detail.