A novel molecular conjugate for the simultaneous DNA oxidation and targeted delivery of nitric oxide triggered by light
Tóm tắt
We have designed and synthesized a novel photoactivable molecular conjugate integrating three basic components in its molecular skeleton: a DNA intercalator, a viologen moiety and a nitric oxide (NO) photodonor. This compound is soluble in aqueous solution and binds to double strand DNA with an association constant of 1.1×104 M−1. The fluorescence of the intercalator unit is strongly quenched due to an intramolecular electron transfer involving the adjacent viologen moiety. Laser flash photolysis measurements provide direct evidence that, in the presence of DNA, this process is followed by a second electron transfer from DNA to the oxidized intercalator, leading to nucleobase oxidation. Also, the light absorbed by the NO photodonor results in the simultaneous release of NO nearby DNA as confirmed by the direct monitoring of this transient species through an ultrasensitive NO electrode. In this view, this conjugate represents an intriguing model system for photoactivable “dual-function” compounds for biomedical research.
Tài liệu tham khảo
See, for example: P. E. Nielsen, Chemical and photochemical probing of DNA complexes, J. Mol. Recognit., 1990, 3, 1–25
Molecular Aspects of Anticancer Drug–DNA Interactions, ed. S. Neidle and M. Waring, CRC, Boca Raton, FL, 1993
G. B. Schuster, Long-range charge transfer in DNA: transient structural distortions control the distance dependance, Acc. Chem. Res., 2000, 33, 253–260
B. Giese, Long-distance charge transport in DNA: the hopping mechanism, Acc. Chem. Res., 2000, 33, 631–636
C. J. Burrows, J. G. Muller, Oxidative nucleobase modifications leading to strand scission, Chem. Rev., 1998, 98, 1109–1152
L. J. Ignarro, Nitric Oxide Biology and Pathobiology, Academic Press, San Diego, CA, 1st edn, 2000, 1003 pp.
E. Culotta, D. E. Koshland, NO news is good news, Science, 1992, 258, 1862–1865
L. J. Ignarro, Nitric oxide: a Unique endogenous signaling molecule in vascular biology, Angew. Chem., Int. Ed., 1999, 38, 1882–1892
F. Murad, Discovery of some of the biological effects of nitric oxide and its role in cell signalling, Angew. Chem., Int. Ed., 1999, 38, 1856–1868
R. F. Furchgott, Endothelium-derived relaxing factor: discovery, early studies, and identifcation as nitric oxide, Angew. Chem., Int. Ed., 1999, 38, 1870–1880
W. Xu, L. Z. Liu, M. Loizidou, M. Ahmed, I. G. Charles, The role of nitric oxide in cancer, Cell Res., 2002, 12, 311–320
B. Mitrovic, L. J. Ignarro, H. V. Vinters, M. A. Akerms, I. Schmid, C. Uittenbogaart, Nitric oxide induces necrotic but not apoptotic cell death in oligodendrocytes, Neuroscience, 1995, 65, 531–539
Y. Hou, J. Wang, P. R. Andreana, G. Cantauria, S. Tarasia, L. Sharp, P. G. Braunschweiger, P. G. Wang, Targeting nitric oxide to cancer cells: cytotoxicity studies of glyco-S-nitrosothiols, Bioorg. Med. Chem. Lett., 1999, 9, 2255–2268
J. B. Hibbs Jr., R. R. Taintor, Z. Vavrin, Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite, Science, 1987, 235, 473–476
T. deRojas-Walker, S. Tamir, H. Ji, J. S. Wishnok, S. R. Tannenbaum, Nitric oxide induces oxidative damage in addition to deamination in macrophage DNA, Chem. Res. Toxicol., 1995, 8, 473–477
K. Fukuhara, M. Kurihara, N. Miyata, Photochemical generation of nitric oxide from 6-nitrobenzo[a]pyrene, J. Am. Chem. Soc., 2001, 123, 8662–8666
D. A. Wink, K. S. Kasprzak, C. M. Maragos, R. K. Elespru, M. Misra, T. M. Dunams, T. A. Celuba, W. H. Koch, A. W. Andrews, J. S. Allen, L. K. Keefer, DNA deaminating ability and genotoxicity of nitric oxide and its progenitors, Science, 1991, 254, 1001–1003
T. Nguyen, D. Brunson, C. L. Crespi, B. W. Penman, J. S. Wishnok, S. R. Tannenbaum, DNA damage and mutation in human cells exposed tonitric oxide in vitro, Proc. Natl. Acad. Sci. U. S. A., 1992, 89, 3030–3034.
P. A. King, V. E. Anderson, J. O. Edwards, G. Gustafson, R. C. Plumb, J. W. Suggs, A stable solid that generates hydroxyl radical upon dissolution in aqueous solutions: reaction with proteins and nucleic acid, J. Am. Chem. Soc., 1992, 114, 5430–5432.
See, for example: B. Armitage, Photocleavage of nucleic acids, Chem. Rev., 1998, 98}, 1171–
P. G. Wang, M. Xian, X. Tang, X. Wu, Z. Wen, T. Cai, A. J. Janczuk, Nitric oxide donors: chemical activities and biological applications, Chem. Rev., 2002, 102, 1091–1134
P. C. Ford, Polychromophoric metal complexes for generating the bioregulatory agent nitric oxide bysingle-and two-photon excitation, Acc. Chem. Res., 2008, 41, 190–200.
F. Callari, S. Sortino, Amplified nitric oxide photorelease in the DNA proximity, Chem. Commun., 2008, 1971–1973
M. Hariharan, J. Joseph, D. Ramaiah, Novel bifunctional viologen-linked pyrene conjugates: synthesis and study of their interactions with nucleosides and DNA, J. Phys. Chem. B, 2006, 110, 24678–24686
J. Joseph, N. V. Eldho, D. Ramaiah, Control of electron-transfer and DNA binding properties by the tolyl spacer group in viologen linked acridines, J. Phys. Chem. B, 2003, 107, 4444–4450
J. Joseph, N. V. Eldho, D. Ramaiah, Design of photoactivated DNA oxidizing agents: Synthesis and study of photophysical properties and DNA interactions of novel viologen-linked acridines, Chem.–Eur. J., 2003, 9, 5926–5935
S. Sortino, S. Petralia, G. Compagnini, S. Conoci, G. Condorelli, Light-controlled nitric oxide generation from a novel self-assembled monolayer on a gold surface, Angew. Chem., Int. Ed., 2002, 41, 1914–1917
E. B. Caruso, S. Petralia, S. Conoci, S. Giuffrida, S. Sortino, Photodelivery of nitric oxide from water-soluble platinum nanoparticles, J. Am. Chem. Soc., 2007, 129, 480–481
E. B. Caruso, E. Cicciarella, S. Sortino, A multifunctional nanoassembly of mesogen-bearing amphiphiles and porphyrins for the simultaneous photodelivery of nitric oxide and singlet oxygen, Chem. Commun., 2007, 5028–5030
L. Valli, G. Giancane, S. Sortino, Nitric Oxide Photoreleasing Multilayer Films, J. Mater. Chem., 2008, 18, 2437–2441
M. Barone, M. T. Sciortino, D. Zaccaria, A. Mazzaglia, S. Sortino, Nitric oxide photocaging platinum nanoparticles with anticancer potential, J. Mater. Chem., 2008, 18, 5531–5536
M. Barone, A. Mascali, S. Sortino, Bifunctional nanoparticle assemblies: photoluminescent and nitric oxide photodelivering monolayer protected platinum clusters, New J. Chem., 2008, 32, 2195–2200
E. Vittorino, E. Cicciarella, S. Sortino, A “dual-function” photocage releasing nitric oxide and an anthrylmethyl cation with a single wavelength, Chem.–Eur. J., 2009, 15, 6802–6806.
S. Conoci, S. Petralia and S. Sortino, Use of nitroaniline derivatives for the production of nitric oxide, U.S. Pat. Appl. Publ., 2009, No. PCT/IT2006/000575.
Irrespective of the ionization conditions, no naked either 2+ monocation or 22+ dications were detected in the ESI-MS spectrum. This situation is very common for compounds in which either viologen dications or pyridinium monocations are linked to benzyl-aryl derivatives. In these cases, the compounds are demonstrated to be intrinsically unstable and readily fragment in the electrospray source stabilizing themselves by formation of single charged fragments. See, for example: C. A. Schalley, C. Verhaelen, F.-G. Kläner, U. Hahn, F. Vögtle, Gas-phase host–guest chemistry of dendritic viologens and molecular tweezers: a remarkably strong effect on dication stability, Angew. Chem., Int. Ed., 2005, 44, 477
V. Gabelica, D. Lemaire, O. Laprévote, E. De, Pauw, Kinetics of solvent addition on electrosprayed ions in an electrospray source and in a quadrupole ion trap, Int. J. Mass Spectrom., 2001, 210–211, 113–119.
The viologen moiety (unit b) does not absorb significantly above 300 nm.
Estimated by the Rehm–Weller equation 15a on the basis of the oxidation potential of anthracene (1.16 V), the reduction potential of viologen (−0.46 V) and the energy of the lowest excited singlet state of anthracene (3.3 eV).15b
D. Rehm, A. Weller, Kinetics of fluorescence quenching by electron and hydrogen-atom transfer, Isr. J. Chem., 1970, 8, 259–271
M. Montalti, A. Credi, L. Prodi and M. T. Gandolfi, Handbook of Photochemistry, CRC Press LLC, Boca Raton, FL, 3rd edn, 2006
See, for example: C. V. Kumar, E. H. Asuncion, DNA binding studies and site selective fluorescence sensitization of an anthryl probe, J. Am. Chem. Soc, 1993, 115, 8547–8553
C. V. Kumar, E. H. Asuncion, Sequence dependent energy transfer from DNA to an anthryl probe: discrimination between GC and IC sequences, Chem. Commun., 1999, 1219–1220. au17_C. V. Kumar, in Photochemistry in Organized and Constrained Media, ed. V. Ramamurthy, VCH Publisher, New York, 1991, pp. 785–816.
A. M. Pyle, J. P. Rehmann, R. Meshoyer, C. V. Kumar, N. J. Turro, J. K. Barton, Mixed-ligand complexes of ruthenium(II): factors governing binding to DNA, J. Am. Chem. Soc., 1989, 111, 3051–3058.
T. Watanabe, K. Honda, Measurement of the extinction coefficient of the methyl viologen cation radical and the efficiency of its formation by semiconductor photocatalysis, J. Phys. Chem., 1982, 86, 2617–2619.
L. P. Candeias, S. Steenken, Structure and acid-base properties of one-electron-oxidized deoxyguanosine, guanosine, and 1-methylguanosine, J. Am. Chem. Soc., 1989, 111, 1094–1099.
The photochemical mechanism for NO photorelease was extensively reported in our previous papers;11a,b,d it involves a nitro -to-nitrite photorearrangement followed by the rupture of the O–N bond to generate a phenoxyl radical and NO.
We emphasize that the present contribution focuses on the demonstration of a proof-of-concept design. Therefore, DNA photocleavage studies would be, at the present, out of the aim of the present work. A study in this perspective will be the object of future investigation.