Chemistry Reference
In-Depth Information
mismatch. Indeed, a direct correlation was observed between the extent to which a
mismatch is destabilized (which depends on the bases involved) and the binding
affi nity of the complex for that mismatch.
61
The complexes exhibited remarkably
specifi c mismatch recognition, with photoactivated DNA cleavage observed at over
80% of mismatch sites, irrespective of the sequence of the mispaired bases involved.
62
Signifi cantly, cleavage was observed at a single-base mismatch in a 2725 base pair
plasmid heteroduplex.
61
Such high specifi city has led to many applications of such
complexes, including investigations into the correlation between defi ciencies in
mismatch repair and cancerous transformations, and towards the development of
novel cancer treatments.
56
Related complexes have also been employed as probes for mismatch occur-
rence;
63,64
as targeting agents for conventional cisplatin chemotherapeutic proto-
cols;
65,66
and as site-specifi c delivery agents for metal-binding peptide conjugates.
67
The complexes developed also inhibit cellular proliferation in mismatch-repair-
defi cient cells (such as those associated with cancerous growth) in preference to
healthy, mismatch - profi cient cells.
68
Such observations have led to complexes
designed for selective chemotherapeutic agents that target mismatches in cancerous,
rather than healthy cells.
68
Recent work has determined the mode of DNA binding involved in mismatch
recognition. The crystal structure of [Rh(bpy)
2
(chrysi)]
3+
bound to a CA mismatch
in a DNA oligonucleotide revealed that, in contrast to earlier reports on the mode
of intercalation, wherein DNA does not unwind to allow intercalation of the new
ligand, the complex inserted into the double helix specifi cally at the mismatch site,
ejecting both mismatched bases, to accommodate the new ligand.
69
Such results
again corroborate the ability of the bulky complex to specifi cally recognize mis-
matches over normal base pairing. Very recently the intercalation of a complex into
a DNA cytosine-cytosine mismatch was identifi ed using NMR solution studies.
70
10.4 Tin - DNA Interactions
10.4.1 Introduction
Tin complexes, in particular organotin species, where a direct C-Sn bond is present
within the complex, have found application in many industries. The widespread use
of organotin complexes in the food, agricultural, paints and polymer industries has
resulted in their accumulative distribution in the environment and in biological
systems. The biological toxicity of tin species is well known, and such species exhibit
a particular toxicity towards the central nervous system. The ability of inorganic
divalent tin to interact with DNA has been established.
71 - 73
Such species were found
to enter human white blood cells, and cause extensive damage to DNA through
oxidative mechanisms. As a consequence, much research has focused on the biologi-
cal effects of organotin complexes.
2,8,23,74,75
Despite the associated toxicity issues,
organotin compounds have found many pharmacological applications, as potential
antiinfl ammatory, antimicrobial and antitumour agents. Understanding the interac-
