Efficient inhibition of photo[2 + 2]cycloaddition of thymidilyl(3'- 5')thymidine and promotion of photosplitting of the cis-syn-cyclobutane thymine dimer by dimeric zinc(II)-cyclen complexes containing m- and p-xylyl spacers

Monomeric and dimeric zinc(II) complexes of cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) inhibited the photo[2 + 2]cycloaddition of thymidilyl(3‘−5‘)thymidine (d(TpT)) at neutral pH in aqueous solution for a novel mechanism. Comparison of the initial rates and the product yields of the photodimerization of d(TpT) (in Tris buffer at pH 7.6 with I = 0.10 (NaNO3)) at 3−5 °C by high-pressure mercury lamp indicates that the dimeric zinc(II) complexes, p- and m-xylyl-bis(Zn2+−cyclen) (Zn2L2 and Zn2L3), are effective inhibitors (70−85% inhibition compared with the control reaction at [d(TpT)] = [bis(Zn2+−cyclen)] = 0.2 mM after 20 min irradiation). This inhibition is due to the extremely strong 1:1 complexation of two deprotonated thymidine (dT-) moieties with two Zn2+−cyclen moieties (apparent complexation constants, log Kapp (Kapp = [Zn2L2 (or Zn2L3)−d(T-pT-)]/[Zn2L2free (or Zn2L3free)][d(TpT)free] (M-1)), of 6.4 ± 0.1 at pH 7.6 (50 mM HEPES, I = 0.1 (NaNO3)) and 25 °C, as determined by the isothermal calo...