Designing Infrared Probes of DNA
Joanne Dyer
School of Chemistry, University of Nottingham, Nottingham, NG7 2RD, UK.
A great deal of attention has been focused on the structural features and electron transfer processes, which occur along the DNA helix and their role in DNA damage. This has resulted in the creation of a wide range of complexes designed to provide an insight into the mechanism of this damage and aid the development of novel diagnostic and chemotherapeutic tools. Transition metal complexes of Ru(II), Rh(III) and Cu(I) with polypyridine ligands which interact strongly with DNA, have been at the forefront of such investigations.[1] Reports on the interactions of related Re(I) complexes with DNA however, have been very limited.[2,3] The latter have highlighted the potential of complexes of the type fac-[(dppz-R'R'')Re(CO)3(L)]+ as DNA probes but their photophysical and photochemical properties remain ambiguous.
Our approach towards the investigation of fac-[(dppz-R'R'')Re(CO)3(L)]+ complexes and their interactions with DNA, invokes the spectroscopic handle provided by the tricarbonyl moiety; infrared vibrational spectroscopy. The sensitivity of the position and bandwidth of n (CO) stretches to their electronic environment is well known, and as a result these are able to act not only as efficient chemical reporters of the photophysical properties of the complex but also of the character of the DNA binding site. Nanosecond and picosecond time-resolved infrared (TRIR) spectroscopy can be used to detect the response of these infrared DNA probe complexes to changes in electronic environment.[4]
A series of fac-[(dppz-R'R'')Re(CO)3(L)]+ complexes have been synthesised and the nature of their excited state properties elucidated by the above methodology, in order to assess their suitability as DNA probes. Of these, fac-[(dppz-NO2)Re(CO)3(4-Me2Npy)]+ has emerged as the most successful candidate as the first infrared DNA probe.[5] A summary of the results leading to the development of this probe and its interaction with DNA will be presented. In addition the interpretation of these results, aided by a study of the infrared spectroelectrochemical properties of the probe, will be discussed.
References
[1]. K. E. Erkkila, D. T. Odom and J. K. Barton, Chem. Rev., 1999, 99, 2777.
[2]. V. W. W. Yam, K. K. W. Lo, K. K. Cheung and R. Y. C. Kong, J. Chem. Soc., Dalton Trans., 1997, 2067.
[3]. H. D. Stoeffler, N. B. Thornton, S. L. Temkin and K. S. Schanze, J. Am. Chem. Soc., 1995, 117, 7119.
[4]. M. W. George and J. J. Turner, Coord. Chem. Rev., 1998, 177, 201.
[5]. J. Dyer, D.C. Grills, P. Matousek, A. W. Parker, M. Towrie, J. A. Weinstein, M. W. George, Chem. Commun., 2002, in press.