Solution studies on trace metal ion interactions with adenine as primary ligand and 5-halouracils as secondary ligands Sudha Singh Department of Chemistry, Banaras Hindu University, Varanasi-221005, India Rajender Singh, Preeti Babbar and Udai P. Singh* Department of Chemistry, University of Roorkee, Roorkee-247667, India Received 22 January 1999; accepted 25 March 1999 Abstract The interaction of trace metal ions, viz. Mn II , Co II , Ni II , Cu II , Zn II and Cd II with adenine (A) as primary ligand and 5-halouracils, viz. 5-bromouracil (5BrU) and 5-iodouracil (5IU) as secondary ligands (L) has been studied at 25  0.1 °C and at constant ionic strength (l = 0.1 M NaNO 3 ), in an aqueous medium using Bjerrum±Calvin's pH-titration technique as adopted by Irving and Rossotti for binary (ML), and by Chidambaram and Bhattacharya for ternary (MAL) systems respectively. The experimental pH-titration data were analyzed with the aid of the BEST computer program in order to evaluate formation constants of various intermediate complex species formed in binary and ternary systems involving nucleobases (viz. A, 5BrU and 5IU). The relative stability of each ternary complex was compared with that of the corresponding binary complexes in terms of Dlog K values. Introduction 5-Halouracils (5XU, where X = F, Cl, Br and I) are best known as DNA base analogs. 5XUs act as chemical mutagens causing mutation in human as well as animals [1±8], inhibitors of protein and nucleic acid synthesis, and are consequently cancerostatic and can act as antiviral agents [9±11]. 5XU compounds have also been extensively investigated as potential anticancer drugs [12, 13], each exhibiting a dierent spectrum of inhibitory eects in dierent animals. Some of these chemotherapeutic compounds have been increasingly employed alone, or in combination with other cytotoxic drugs and hormones in the medical treatment of dierent kinds of tumours [14]. The antitumour activity of 5XU against dierent tumour systems have also been reported to be markedly enhanced by the co-adminis- tration of purine derivatives, resulting in therapeutic synergism [15]. Adenine (A) is one of the most common naturally occurring purine derivatives, found invariably in almost all the living tissues as components of nucleic acids, many antibiotics and various coenzyme systems. It is also found in all the living cells as the mono-, di- and triphosphate of A-nucleosides, viz. adenosine monopho- sphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) which play vital roles in many metabollic processes. (A) has also been reported to possess chelating properties. Many of these drugs have an increased anticancer activity when administered as metal complexes [16±22]. In spite of numerous papers describing the antitumour and antirheumatic eects of 5XU [23±26] and its metal complexes [23, 27, 28] in a number of animals and men, information on the chemotherapeutic properties of 5XU in the presence of its complementary nucleobases (i.e. A and G), and metal-base pair complexes is not available in the literature. Hence, the studies on the formation of metal complexes of 5XU in the presence of its complementary purine base (A) are of considerable importance. Moreover, in living systems, almost all the biochem- ical processes are known to proceed mostly in the solution phase where several metal ions are present in trace quantities. Most of the physiological activities regarding nucleic acid interactions are promoted by metal ions through the formation of ternary (mixed- ligand) complexes [29±34]. Whenever a metal ion exists in solution together with two or more dierent ligands, the formation of various simple as well as ternary (mixed-ligand) complexes is always possible, depending on the pH of the system. The actual complex-formation depends on the anity of the metal ion towards the various ligands present, and the relative concentrations thereof. Therefore, keeping the chemotherapeutic and mutagenic properties of 5XU and importance of their complexation with metal ions under physiological conditions in mind, in this paper the formation of binary and ternary complexes of manganese(II), cobalt(II), * Author for correspondence Transition Metal Chemistry 25: 9±16, 2000. 9 Ó 2000 Kluwer Academic Publishers. Printed in the Netherlands.