Bis-intercalation of homodimeric thiazole orange dye derivatives in DNA

The thiazole orange dye 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundeeamethylene) -bis-4-[(3-methyl-2,3-dihydro-2 (3H)-benzo-1,3-thiazolylidene)methyl] quino linium tetraiodide (TOTO) binds to double-stranded DNA (dsDNA) in a sequenc e selective bis-intercalation. We have examined the binding of derivatives of TOTO with different substituents on the benzothiazole ring. The analogue s are the following: 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-[4 -[3-(benzyl-2,3-dihydro-2-(3H)-benzothiazolylidene)methol]quinolinium]-[4-[ 3-(methyl-2,3-dihydro-2-(3H)-benzothiazolylidene)methyl]quniolinium]tetraio dide (TOTOBzl) and 1,1'-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis- 4-[(3-ethyl-2,3-dihydro-2(3H)-benzo-1,3-thiazole)methyl]quinolinium tetraio dide (TOTOEt). In this paper, we report the synthesis of TOTOBzl and TOTOEt together with the one- and two-dimensional H-1 NMR investigations of compl exes between these TOTO analogues and the dsDNA oligonucleotide d(CGCTAGCG) (2). Both analogues yield extremely stable complexes in which each chromoph ore is sandwiched between two base pairs in a (5'-CpT-3'):(5'-ApG-3') site. The linker spans over two base pairs in the minor groove. The benzyl group in TOTOBzl and the ethyl groups in TOTOEt is pointing outward in the major groove.