title: Charge and substituent effects on the stability of porphyrin/G-quadruplex adducts.
abstract: 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 + nNH(4)(+)+P(p+)-(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)(+)+P(p+)-(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 + P(p+)-(z + p)H(+)](z-) predominates for porphyrins with a higher number of positive charges. Strand separation with the formation of [T + P(p+)-(z-2 + p)H(+)]((z-2)-) and (SS-2H(+))(2-) ions, where T = [d(TG(4)T)](3) and [d(T(2)G(5)T)](3) and SS = d(TG(4)T) and d(T(2)G(5)T) is only observed for the complexes with a higher overall negative charge. Porphyrin loss with the formation of [Q + nNH(4)(+)-(z + n)H(+)](z-) ions occurs predominantly for the neutral and monocharged porphyrins. The predominant formation of the 'unfilled' ions, [Q + P(p+)-(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.
authors.affiliation: Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Catarina I V
authors.initials: CI
authors.lastname: Ramos
authors.forename: João P C
authors.initials: JP
authors.lastname: Tomé
authors.forename: M G
authors.initials: MG
authors.lastname: Santana-Marques
mesh_terms: D018736:DNA Adducts / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D011166:Porphyrins / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D018736:DNA Adducts; D011166:Porphyrins