| Abstract
| - The thiazole orange dye1,1‘-(4,4,8,8-tetramethyl-4,8-diazaundecamethylene)-bis[4-[3-methyl-2,3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinoliniumtetraiodide (TOTO) binds to double-strandedDNA (dsDNA) in a sequence selective bisintercalation. Eachchromophore is sandwiched betweentwo base pairs in a (5‘-CpT-3‘):(5‘-ApG-3‘) site, and the linker spansover two base pairs in the minorgroove. The binding of analogs of TOTO in which the linker hasbeen modified is examined. The aimof the study is to utilize the sequence selectivity of the TOTOchromophores to enhance and/or alterthe overall selectivity of the binding. One- and two-dimensional1H-NMR investigations of complexesbetween TOTO analogs and various dsDNA oligonucleotides are reported.The following analogs weresynthesized and used: 1,1‘-(4,4,8,8-tetramethyl-4,8-diazadodecamethylene)-bis[4-[3-methyl-2,3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinolinium tetraiodide(TOTO10), 1,1‘-(5,5,9,9-tetramethyl-5,9-diazatridecamethylene)-bis[4-[3-methyl-2,3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinoliniumtetraiodide (TOTO11), and1,1‘-(6,6,10,10-tetramethyl-6,10-diazapentadecamethylene)-bis[4-[3-methyl-2,3-dihydro(benzo-1,3-thiazole)-2-methylidene]]quinoliniumtetraiodide (TOTO13). The results showthat with a longer linker the dyes can bisintercalate into two(5‘-CpT-3‘):(5‘-ApG-3‘) sites separatedby one or two base pairs. Bisintercalation in two such“isolated” binding sites yields non-nearest-neighbor bisintercalation in which the linker spans over more than twobase pairs. The investigationsalso showed that an exact length of the linker is not crucial for thesite selectivity since TOTO, TOTO10,and TOTO11 are almost equally suitable in binding selectively to the(5‘-CTAG-3‘)2 sequence.Fluorescence measurements show that TOTO10, TOTO11, and TOTO13have higher fluorescencequantum yields than TOTO when bound to d(CGCTAGCG)2.This indicates that the length of thelinker in TOTO may not be the optimum one in terms of using the dye asa fluorescence marker.
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