Charge and substituent effects on the stability of porphyrin/G-quadruplex adducts

The adduct ions of two tetramolecular G-quadruplexes formed from the d(TGGGGT) and d(TTGGGGGT) single strands with a group of cationic porphyrins, with different charges and substituents, and one neutral porphyrin, were investigated by ESI-MS and ESI-MS/MS in the negative ion mode. Formation of [Q?+?nNH4++Pp+-(z?+?n?+?p)H+]z- adduct ions (where Q?=?quadruplex, n?=?number of quartets minus 1, P?=?porphyrin and p+ =0,1,2,3,4) indicates that the porphyrins are bound outside the quadruplexes providing an additional stabilization to those structures. The fragmentation pathways of the [Q + nNH(4)(+)+ Pp+-(z + n + p) H+](z-) adduct ions depend on the number of positive charges (p(+)) of the porphyrins and on the overall complex charge (z-), but do not show a significant dependence on the type of the substituent groups in the porphyrins. Formation of the 'unfilled' ions [Q + Pp+-(z + p)(H+)](z-) predominates for porphyrins with a higher number of positive charges. Strand separation with the formation of [T + Pp+-(z-2 + p)H+]((z-2)-) and (SS- 2H+) 2- ions, where T = [d(TG4T)] 3 and [d(T2G5T)] 3 and SS = d(TG4T) and d(T2G5T) is only observed for the complexes with a higher overall negative charge. Porphyrin loss with the formation of [Q + nNH4 +-(z + n) H+] z- ions occurs predominantly for the neutral and monocharged porphyrins. The predominant formation of the ` unfilled' ions, [Q + Pp+-(z + n) H+] z-, for porphyrins with a higher number of charges shows that these porphyrins can prevent strand separation and preserve, at least partially, the quadruplex structure. Copyright c 2012 John Wiley & Sons, Ltd.