Speciation 98: Abstracts

Aminoglycoside antibiotics play an important role in modern therapy, ranging from household skin ointments to general sepsis treatments in intensive therapy wards. They are very efficient against a broad range of bacterial pathogens. Their usage is limited, however, by very narrow windows of therapeutical concentrations and severe oto- and nephrotoxicity when threshold concentrations are exceeded.

Molecules of aminoglycosides are a combination of aminosugar and aminocyclitol rings. They usually contain 4-6 amino groups, which are essential for their biological activities. Our previous studies ¹ indicated that aminosugars are very good {N,O} ligands for Cu(II) ions. We also provided evidence that such co-ordination results in strong oxygen activation. ² Having these results in mind, we performed studies of Cu(II) binding by several aminoglycosides ^3-6 and investigated the oxygen activation using 2'-deoxyguanosine as reporter molecule. ^3,4 The results of these studies can be summarised as follows:

(i) unsubstituted aminoglycosides ^4-6 use aminosugar-like {N,O}chelates to bind Cu(II), despite the presence of a pair of suitably located amino groups in their deoxystreptamine (B) ring. However, amidation of one of these nitrogens in amikacin ³ makes B ring the sole binding site;
(ii) the C-ring is the anchoring site for Cu(II) in unsubstituted aminoglycosides at pH 5-6. At higher pH the A-ring donors participate in the binding of the same Cu(II) ion, forming a macrochelate assembly;
(iii) oxygen activation is a common feature of Cu(II) complexes of aminoglycosides. ^2-4 These properties, together with model biospeciation studies performed for amikacin,³ suggest that the Cu(II) binding may be an element of bioactivity of aminoglycosides.

References

1. M. Jezowska-Bojczuk, S. Lamotte, and T. Trnka, J. Inorg. Biochem. 61, 213-219 (1996) and references therein.
2. M. Jezowska-Bojczuk, W. Bal, and K. S. Kasprzak, J. Inorg. Biochem. 64, 231-246 (1996).
3. M. Jezowska-Bojczuk and W. Bal, J. Chem. Soc. Dalton Trans. 153-159 (1998).
4. M. Jezowska-Bojczuk, W.Bal and H. Kozlowski, Inorg. Chim. Acta, in the press.
5. M. Jezowska-Bojczuk, A. Karaczyn and H. Kozlowski, Polyhedron, submitted.
6. M. Jezowska-Bojczuk, A. Karaczyn and W. Bal, J. Inorg. Biochem., submitted.

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