Electron-driven proton transfer relieves excited-state antiaromaticity in photoexcited DNA base pairs.
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ABSTRACT: The Watson-Crick A·T and G·C base pairs are not only electronically complementary, but also photochemically complementary. Upon UV irradiation, DNA base pairs undergo efficient excited-state deactivation through electron driven proton transfer (EDPT), also known as proton-coupled electron transfer (PCET), at a rate too fast for other reactions to take place. Why this process occurs so efficiently is typically reasoned based on the oxidation and reduction potentials of the bases in their electronic ground states. Here, we show that the occurrence of EDPT can be traced to a reversal in the aromatic/antiaromatic character of the base upon photoexcitation. The Watson-Crick A·T and G·C base pairs are aromatic in the ground state, but the purines become highly antiaromatic and reactive in the first 1ππ* state, and transferring an electron and a proton to the pyrimidine relieves this excited-state antiaromaticity. Even though proton transfer proceeds along the coordinate of breaking a N-H σ-bond, the chromophore is the π-system of the base, and EDPT is driven by the strive to alleviate antiaromaticity in the π-system of the photoexcited base. The presence and absence of alternative excited-state EDPT routes in base pairs also can be explained by sudden changes in their aromatic and antiaromatic character upon photoexcitation.
Project description:Baird's rule explains why and when excited-state proton transfer (ESPT) reactions happen in organic compounds. Bifunctional compounds that are [4n + 2] ?-aromatic in the ground state, become [4n + 2] ?-antiaromatic in the first 1??* states, and proton transfer (either inter- or intramolecularly) helps relieve excited-state antiaromaticity. Computed nucleus-independent chemical shifts (NICS) for several ESPT examples (including excited-state intramolecular proton transfers (ESIPT), biprotonic transfers, dynamic catalyzed transfers, and proton relay transfers) document the important role of excited-state antiaromaticity. o-Salicylic acid undergoes ESPT only in the "antiaromatic" S1 (1??*) state, but not in the "aromatic" S2 (1??*) state. Stokes' shifts of structurally related compounds [e.g., derivatives of 2-(2-hydroxyphenyl)benzoxazole and hydrogen-bonded complexes of 2-aminopyridine with protic substrates] vary depending on the antiaromaticity of the photoinduced tautomers. Remarkably, Baird's rule predicts the effect of light on hydrogen bond strengths; hydrogen bonds that enhance (and reduce) excited-state antiaromaticity in compounds become weakened (and strengthened) upon photoexcitation.
Project description:The UV spectra of three different conformers of the guanine/cytosine base pair were recorded recently with UV-IR double-resonance techniques in a supersonic jet [Abo-Riziq, A., Grace, L., Nir, E., Kabelac, M., Hobza, P. & de Vries, M. S. (2005) Proc. Natl. Acad. Sci. USA 102, 20-23]. The spectra provide evidence for a very efficient excited-state deactivation mechanism that is specific for the Watson-Crick structure and may be essential for the photostability of DNA. Here we report results of ab initio electronic-structure calculations for the excited electronic states of the three lowest-energy conformers of the guanine/cytosine base pair. The calculations reveal that electron-driven interbase proton-transfer processes play an important role in the photochemistry of these systems. The exceptionally short lifetime of the UV-absorbing states of the Watson-Crick conformer is tentatively explained by the existence of a barrierless reaction path that connects the spectroscopic (1)pi pi * excited state with the electronic ground state via two electronic curve crossings. For the non-Watson-Crick structures, the photochemically reactive state is located at higher energies, resulting in a barrier for proton transfer and, thus, a longer lifetime of the UV-absorbing (1)pi pi * state. The computational results support the conjecture that the photochemistry of hydrogen bonds plays a decisive role for the photostability of the molecular encoding of the genetic information in isolated DNA base pairs.
Project description:The use of light to drive proton-coupled electron transfer (PCET) reactions has received growing interest, with recent focus on the direct use of excited states in PCET reactions (ES-PCET). Electrostatic ion pairs provide a scaffold to reduce reaction orders and have facilitated many discoveries in electron-transfer chemistry. Their use, however, has not translated to PCET. Herein, we show that ion pairs, formed solely through electrostatic interactions, provide a general, facile means to study an ES-PCET mechanism. These ion pairs formed readily between salicylate anions and tetracationic ruthenium complexes in acetonitrile solution. Upon light excitation, quenching of the ruthenium excited state occurred through ES-PCET oxidation of salicylate within the ion pair. Transient absorption spectroscopy identified the reduced ruthenium complex and oxidized salicylate radical as the primary photoproducts of this reaction. The reduced reaction order due to ion pairing allowed the first-order PCET rate constants to be directly measured through nanosecond photoluminescence spectroscopy. These PCET rate constants saturated at larger driving forces consistent with approaching the Marcus barrierless region. Surprisingly, a proton-transfer tautomer of salicylate, with the proton localized on the carboxylate functional group, was present in acetonitrile. A pre-equilibrium model based on this tautomerization provided non-adiabatic electron-transfer rate constants that were well described by Marcus theory. Electrostatic ion pairs were critical to our ability to investigate this PCET mechanism without the need to covalently link the donor and acceptor or introduce specific hydrogen bonding sites that could compete in alternate PCET pathways.
Project description:Electron-induced proton transfer depicts the proton motion coupled with the attachment of a low-energy electron to a molecule, which helps to understand copious fundamental chemical processes. Intramolecular electron-induced proton transfer is a similar process that occurs within a single molecule. To date, there is only one known intramolecular example, to the best of our knowledge. By studying the 10-hydroxybenzo[h]quinoline and 8-hydroxyquinoline molecules using anion photoelectron spectroscopy and density functional theory, and by theoretical screening of six other molecules, here we show the intramolecular electron-induced proton transfer capability of a long list of molecules that meanwhile have the excited-state intramolecular proton transfer property. Careful examination of the intrinsic electronic signatures of these molecules reveals that these two distinct processes should occur to the same category of molecules. Intramolecular electron-induced proton transfer could have potential applications such as molecular devices that are responsive to electrons or current.
Project description:Bimolecular excited-state proton-coupled electron transfer (PCET*) was observed for reaction of the triplet MLCT state of [(dpab)2Ru(4,4'-dhbpy)]2+ (dpab = 4,4'-di(n-propyl)amido-2,2'-bipyridine, 4,4'-dhbpy = 4,4'-dihydroxy-2,2'-bipyridine) with N-methyl-4,4'-bipyridinium (MQ+) and N-benzyl-4,4'-bipyridinium (BMQ+) in dry acetonitrile solutions. The PCET* reaction products, the oxidized and deprotonated Ru complex, and the reduced protonated MQ+ can be distinguished from the excited state electron transfer (ET*) and the excited state proton transfer (PT*) products by the difference in the visible absorption spectrum of the species emerging from the encounter complex. The observed behavior differs from that of reaction of the MLCT state of [(bpy)2Ru(4,4'-dhbpy)]2+ (bpy = 2,2'-bipyridine) with MQ+, where initial ET* is followed by diffusion-limited proton transfer from the coordinated 4,4'-dhbpy to MQ0. The difference in observed behavior can be rationalized based on changes in the free energies of ET* and PT*. Substitution of bpy with dpab results in the ET* process becoming significantly more endergonic and the PT* reaction becoming somewhat less endergonic.
Project description:Deracemization is an attractive strategy for asymmetric synthesis, but intrinsic energetic challenges have limited its development. Here, we report a deracemization method in which amine derivatives undergo spontaneous optical enrichment upon exposure to visible light in the presence of three distinct molecular catalysts. Initiated by an excited-state iridium chromophore, this reaction proceeds through a sequence of favorable electron, proton, and hydrogen-atom transfer steps that serve to break and reform a stereogenic C-H bond. The enantioselectivity in these reactions is jointly determined by two independent stereoselective steps that occur in sequence within the catalytic cycle, giving rise to a composite selectivity that is higher than that of either step individually. These reactions represent a distinct approach to creating out-of-equilibrium product distributions between substrate enantiomers using excited-state redox events.
Project description:Graphene quantum dots (GQDs) were connected to [Ru(bpy)3]2+ to sense DNA-mediated charge transfer. Interaction between abasic site double stranded DNA (Abasic-DNA) and [Ru(bpy)3-GQD]2+ was investigated by absorption spectroscopy, gel electrophoresis, circular dichroism, and melting temperature measurements. The results indicate that [Ru(bpy)3-GQD]2+ could be intercalated into double stranded DNA. Using [Ru(bpy)3-GQD]2+ as a signal molecule, the charge transfer performance of DNA-intercalated [Ru(bpy)3-GQD]2+ was determined using electrochemical and electrochemiluminescence measurements. Various DNA types were immobilized on Au electrodes via Au-S bonds. Electrochemiluminescence and electrochemical measurements indicate that [Ru(bpy)3-GQD]2+ could enhance DNA-mediated charge transfer when intercalated into an abasic site of double stranded DNA. And comparing with [Ru(bpy)3]2+, it can be concluded that GQDs intercalate into the DNA duplex by acting as a base analog, thus enhancing DNA charge transfer. These findings suggest that the DNA-GQD structure could aid the development of molecular devices and electric drivers, and broaden the application of DNA charge transfer.
Project description:Photosensitization by drugs is directly related with the excited species and the photoinduced processes arising from interaction with UVA light. In this context, the ability of gefitinib (GFT), a tyrosine kinase inhibitor (TKI) used for the treatment of a variety of cancers, to induce phototoxicity and photooxidation of proteins has recently been demonstrated. In principle, photodamage can be generated not only by a given drug but also by its photoactive metabolites that maintain the relevant chromophore. In the present work, a complete study of O-desmorpholinopropyl gefitinib (GFT-MB) has been performed by means of fluorescence and ultrafast transient absorption spectroscopies, in addition to molecular dynamics (MD) simulations. The photobehavior of the GFT-MB metabolite in solution is similar to that of GFT. However, when the drug or its metabolite are in a constrained environment, i.e. within a protein, their behavior and the photoinduced processes that arise from their interaction with UVA light are completely different. For GFT in complex with human serum albumin (HSA), locally excited (LE) singlet states are mainly formed; these species undergo photoinduced electron transfer with Tyr and Trp. By contrast, since GFT-MB is a phenol, excited state proton transfer (ESPT) to form phenolate-like excited species might become an alternative deactivation pathway. As a matter of fact, the protein-bound metabolite exhibits higher fluorescence yields and longer emission wavelengths and lifetimes than GFT@HSA. Ultrafast transient absorption measurements support direct ESPT deprotonation of LE states (rather than ICT), to form phenolate-like species. This is explained by MD simulations, which reveal a close interaction between the phenolic OH group of GFT-MB and Val116 within site 3 (subdomain IB) of HSA. The reported findings are relevant to understand the photosensitizing properties of TKIs and the role of biotransformation in this type of adverse side effects.
Project description:The dynamics of excited-state double proton transfer of model DNA base pairs, 7-azaindole dimers, is reported using femtosecond fluorescence spectroscopy. To elucidate the nature of the transfer in the condensed phase, here we examine variation of solvent polarity and viscosity, solute concentration, and isotopic fractionation. The rate of proton transfer is found to be significantly dependent on polarity and on the isotopic composition in the pair. Consistent with a stepwise mechanism, the results support the presence of an ionic intermediate species which forms on the femtosecond time scale and decays to the final tautomeric form on the picosecond time scale. We discuss the results in relation to the molecular motions involved and comment on recent claims of concerted transfer in the condensed phase. The nonconcerted mechanism is in agreement with previous isolated-molecule femtosecond dynamics and is also consistent with the most-recent high-level theoretical study on the same pair.
Project description:Visible light excitation of the ligand-bridged assembly [(bpy)(2)Ru(a)(II)(L)Ru(b)(II)(bpy)(OH(2))(4+)] (bpy is 2,2'-bipyridine; L is the bridging ligand, 4-phen-tpy) results in emission from the lowest energy, bridge-based metal-to-ligand charge transfer excited state (L(-•))Ru(b)(III)-OH(2) with an excited-state lifetime of 13 ± 1 ns. Near-diffusion-controlled quenching of the emission occurs with added HPO(4)(2-) and partial quenching by added acetate anion (OAc(-)) in buffered solutions with pH control. A Stern-Volmer analysis of quenching by OAc(-) gave a quenching rate constant of k(q) = 4.1 × 10(8) M(-1) • s(-1) and an estimated pK(a)* value of ~5 ± 1 for the [(bpy)(2)Ru(a)(II)(L(•-))Ru(b)(III)(bpy)(OH(2))(4+)]* excited state. Following proton loss and rapid excited-state decay to give [(bpy)(2)Ru(a)(II)(L)Ru(b)(II)(bpy)(OH)(3+)] in a H(2)PO(4)(-)/HPO(4)(2-) buffer, back proton transfer occurs from H(2)PO(4)(-) to give [(bpy)(2)Ru(a)(II)(L)Ru(b)(bpy)(OH(2))(4+)] with k(PT,2) = 4.4 × 10(8) M(-1) • s(-1). From the intercept of a plot of k(obs) vs. [H(2)PO(4)(-)], k = 2.1 × 10(6) s(-1) for reprotonation by water providing a dramatic illustration of kinetically limiting, slow proton transfer for acids and bases with pK(a) values intermediate between pK(a)(H(3)O(+)) = -1.74 and pK(a)(H(2)O) = 15.7.