Direct Observation of Guanine Radical Cation Deprotonation in G‑Quadruplex DNA Lidan Wu, ‡ Kunhui Liu, ‡ Jialong Jie, Di Song, and Hongmei Su* Beijing National Laboratory for Molecular Sciences (BNLMS), Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China * S Supporting Information ABSTRACT: Although numerous studies have been devoted to the charge transfer through double-stranded DNA (dsDNA), one of the major problems that hinder their potential applications in molecular electronics is the fast deprotonation of guanine cation (G +• ) to form a neutral radical that can cause the termination of hole transfer. It is thus of critical importance to explore other DNA structures, among which G-quadruplexes are an emerging topic. By nanosecond laser flash photolysis, we report here the direct observation and findings of the unusual deprotonation behavior (loss of amino proton N 2 -H instead of imino proton N 1 -H) and slower (1-2 orders of magnitude) deprotonation rate of G +• within G-quadruplexes, compared to the case in the free base dG or dsDNA. Four G-quadruplexes AG 3 (T 2 AG 3 ) 3 , (G 4 T 4 G 4 )2, (TG 4 T)4, and G 2 T 2 G 2 TGTG 2 T 2 G 2 (TBA) are measured systematically to examine the relationship of deprotonation with the hydrogen-bonding surroundings. Combined with in depth kinetic isotope experiments and pK a analysis, mechanistic insights have been further achieved, showing that it should be the non-hydrogen- bonded free proton to be released during deprotonation in G-quadruplexes, which is the N 2 -H exposed to solvent for G bases in G-quartets or the free N 1 -H for G base in the loop. The slower N 2 -H deprotonation rate can thus ensure less interruption of the hole transfer. The unique deprotonation features observed here for G-quadruplexes open possibilities for their interesting applications as molecular electronic devices, while the elucidated mechanisms can provide illuminations for the rational design of G-quadruplex structures toward such applications and enrich the fundamental understandings of DNA radical chemistry. ■ INTRODUCTION The charge transfer through deoxyribonucleic acid (DNA) strands has attracted considerable attention during the past few decades due to its biological importance 1 and potential applications in molecular electronics. 2,3 Especially, a large number of studies 4-8 have been carried out on hole transfer in double-stranded DNA (dsDNA) which is believed to be a promising candidate for developing electronic devices. 9-11 As is well-known, guanine (G) has the lowest oxidation potential among the four DNA bases and is the most readily oxidized base. 12,13 Therefore, for the hole transfer in DNA, the injected hole is always trapped in guanine, and the migration of hole in DNA is consequently a short distance charge-transfer process between stacked guanine bases. 14-16 During the process, the deprotonation of guanine cation radical (G +• ) to form neutral radical (G-H • ) is considered to be the most critical reaction in competition with hole transfer in DNA. 17-19 Due to the fast deprotonation of G +• in dsDNA (with a rate constant of 10 6 to 10 7 s -1 ), 17,18 the distance of dsDNA-mediated hole transfer is limited to be slightly >200 Å. 5,6 To overcome this limit that has hindered hole transfer over longer distance, which has been key to the application of DNA molecules in molecular electronic devices for decades, it is of critical importance to explore other DNA structures with efficient conductivity and slower deprotonation rate. G-quadruplexes are an emerging topic for developing DNA- based molecular electronic devices because of their unique hole-trapping property and their high conductance. 20-25 These advantages are due to the highly ordered DNA structures arising from the self-assembly of particular G-rich DNA sequences. 26 The unique structure of G-quadruplex consists of stacked G-quartets where each G-quartet, as shown in Scheme 1, is a planar array of four Hoogsteen-bonded guanines, Received: October 7, 2014 Published: December 15, 2014 Scheme 1. Model Structure of G-Quartet and GC Base Pair Article pubs.acs.org/JACS © 2014 American Chemical Society 259 DOI: 10.1021/ja510285t J. Am. Chem. Soc. 2015, 137, 259-266