The sulfonylureas have a wide range use in biology, and many of their ramifications have been used as anti-diabetic medicine and herbicide.1,2) Sulfonylurea regulating biological functions of pancreatic islets, which has been used for the treatment of type 2 diabetes mellitus because of its insulin tropic activity on pancreatic islets.3) Subsequent interests were focused on the redox properties, structures and biological activity of their transition metal complexes.4) More recently, the lanthanide(III) complexes of sulfonylurea increasingly attracted attention, because of their certain anti-diabetic activities. Yet it is noticed that the DNA-binding investigation of such complexes have been done relatively few. Because the interaction between metal complexes and DNA is in close relationship with their potential biological and pharmaceutical activities, 5,6) studies on DNA-binding of metal complexes are very important in the development of new therapeutic reagents and DNA molecular probes. In order to find more effective and less toxic anti-diabetic drugs, thousands of analogues of sulfonlyureas were synthesized.
6,7)Here, we synthesized 1-cyclohexyl-3-tosylurea (H 2 L) and its two lanthanide(III) complexes. In addition DNA-binding property of two lanthanide(III) complexes with 1-cyclohexyl-3-tosylurea is reported in this paper. These lanthanide compounds possibly represent a new class of potential anti-diabetic agent.
ExperimentalMaterials Nitroblue tetrazolium (NBT), methionine (MET), vitamin B 2 (VitB 2 ) were purchased from Sigma Chemical Co. Calf thymus DNA (CT-DNA) was purchased from Sigma without further purification. EDTA and Ln 2 O 3 (LnϭNd, Eu) were produced in China. All chemicals used were of analytical grade. The lanthanide(III) nitrates were prepared by dissolving Ln 2 O 3 in HNO 3 , and then crystallizing to get the products. All the experiments involving interaction of the ligand and the complexes with CT-DNA were carried out in doubly distilled water buffer containing 5 mM Tris[Tris(hydroxymethyl)-aminomethane] and 50 mM NaCl, and adjusted to pH 7.2 with hydrochloric acid. A solution of CT-DNA gave a ratio of UV absorbance at 260 and 280 nm of about 1.8-1.9, indicating that the CT-DNA was sufficiently free of protein.8) The CT-DNA concentration per nucleotide was determined spectrophotometrically by employing an extinction coefficient of 6600 M Ϫ1 cm Ϫ1 at 260 nm.9) The ligand and the complexes were dissolved in a solvent mixture of 1% CH 3 OH and 99% Tris-HCl buffer (5 mM Tris-HCl, 50 mM NaCl, pH 7.2) at concentration 1.0ϫ10 Ϫ5 M. An absorption titration experiment was performed by maintaining 10 mM compounds and varying the concentration of nucleic acid. While measuring the absorption spectra, an equal amount of CT-DNA was added to both the compound solution and the reference solution to eliminate the absorbance of CT-DNA itself. EDTA-Fe(II) and Na 2 HPO 4 -KH 2 PO 4 buffers were prepared with twice distilled water.Physical Measurements The melting points of the compounds were determined on a B...