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1.
J Phys Chem Lett ; 10(22): 7133-7140, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31652065

RESUMO

In humans, vision is limited to a small fraction of the whole electromagnetic spectrum. One possible strategy for enhancing vision in deep-red or poor-light conditions consists of recruiting chlorophyll derivatives in the rod photoreceptor cells of the eye, as suggested in the case of some deep-sea fish. Here, we employ all-atom molecular simulations and high-level quantum chemistry calculations to rationalize how chlorin e6 (Ce6), widely used in photodynamic therapy although accompanied by enhanced visual sensitivity, mediates vision in the dark, shining light on a fascinating but largely unknown molecular mechanism. First, we identify persistent interaction sites between Ce6 and the extracellular loops of rhodopsin, the transmembrane photoreceptor protein responsible for the first steps in vision. Triggered by Ce6 deep-red light absorption, the retinal within rhodopsin can be isomerized thus starting the visual phototransduction cascade. Our data largely exclude previously hypothesized energy-transfer mechanisms while clearly lending credence to a retinal isomerization indirectly triggered by singlet oxygen, proposing an alternative mechanism to rationalize photosensitizer-mediated night vision.

2.
Antioxidants (Basel) ; 8(10)2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31658666

RESUMO

The DNA-binding of the natural benzophenanthridine alkaloid chelerythrine (CHE) has been assessed by combining molecular modeling and optical absorption spectroscopy. Specifically, both double-helical (B-DNA) and G-quadruplex sequences-representative of different topologies and possessing biological relevance, such as telomeric or regulatory sequences-have been considered. An original multiscale protocol, making use of molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculations, allowed us to compare the theoretical and experimental circular dichroism spectra of the different DNA topologies, readily providing atomic-level details of the CHE-DNA binding modes. The binding selectivity towards G-quadruplexes is confirmed by both experimental and theoretical determination of the binding free energies. Overall, our mixed computational and experimental approach is able to shed light on the interaction of small molecules with different DNA conformations. In particular, CHE may be seen as the building block of promising drug candidates specifically targeting G-quadruplexes for both antitumoral and antiviral purposes.

3.
Anal Chem ; 91(20): 12808-12818, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31490660

RESUMO

The number of studies referring to the structural elucidation of intact biomolecular systems using mass spectrometry techniques has gradually increased in the post-2000s literature topics. As part of native mass spectrometry, this domain capitalizes on the kinetic trapping of physiological folds in view of probing solution-like conformational properties of isolated molecules or complexes after their electrospray transfer to the gas phase. Despite its efficiency for a wide array of analytes, this approach is expected to be pushed to its limits when considering highly dynamic systems or when dealing with nonideal operating conditions. To circumvent these limitations, we challenge the adequacy of an original strategy based on cross-linkers to improve the gas-phase stability of isolated proteins and ensure the preservation of folded conformations when measuring with strong transmission voltages, by spraying from denaturing solvents, or trapping for extended periods of time. Tested on cytochrome c, myoglobin, and ß-lactoglobulin cross-linked using BS3, we validated the process as structurally nonintrusive in solution using far-ultraviolet circular dichroism and unraveled the preservation of folded conformations showing better resilience to denaturation on cross-linked species using ion mobility. The resulting collision cross sections were found in agreement with the native fold, and a preservation of the proteins' secondary and tertiary structures was evidenced using molecular dynamics simulations. Our results provide new insights concerning the fate of electro-sprayed cross-linked conformers in the gas phase, while constituting promising evidence for the validation of this technique as part of future structural mass spectrometry workflows.

4.
Chemistry ; 25(10): 2519-2526, 2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30379366

RESUMO

A computational investigation of the triplet excited states of a rhenium complex electronically coupled with a tryptophan side chain and bound to an azurin protein is presented. In particular, by using high-level molecular modeling, evidence is provided for how the electronic properties of the excited-state manifolds strongly depend on coupling with the environment. Indeed, only upon explicitly taking into account the protein environment can two stable triplet states of metal-to-ligand charge transfer or charge-separated nature be recovered. In addition, it is also demonstrated how the rhenium complex plus tryptophan system in an aqueous environment experiences too much flexibility, which prevents the two chromophores from being electronically coupled. This occurrence disables the formation of a charge-separated state. The successful strategy requires a multiscale approach of combining molecular dynamics and quantum chemistry. In this context, the strategy used to parameterize the force fields for the electronic triplet states of the metal complex is also presented.


Assuntos
Azurina/química , Complexos de Coordenação/metabolismo , Pseudomonas aeruginosa/química , Rênio/química , Água/química , Complexos de Coordenação/química , Ligantes , Modelos Moleculares
5.
Chem Sci ; 9(41): 7902-7911, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30450180

RESUMO

The intrinsic photostability of nucleic acids is intimately related to evolution of life, while its understanding at the molecular and electronic levels remains a challenge for modern science. Among the different decay pathways proposed in the last two decades, the excited-state hydrogen transfer between guanine-cytosine base pairs has been identified as an efficient non-reactive channel to dissipate the excess of energy provided by light absorption. The present work studies the dynamics of such phenomena taking place in a (dG)·(dC) B-DNA homopolymer in water solution using state-of-the-art molecular modelling and simulation methods. A dynamic effect that boosts the photostability of the inter-strand hydrogen atom transfers, inherent to the Watson-Crick base pairing, is unveiled and ascribed to the energy released during the proton transfer step. Our results also reveal a novel mechanism of DNA decay named four proton transfer (FPT), in which two protons of two adjacent G-C base pairs are transferred to form a biradical zwitterionic intermediate. Decay of the latter intermediate to the ground state triggers the transfer of the protons back to the guanine molecules recovering the Watson-Crick structure of the tetramer. This FPT process is activated by the close interaction of a nearby Na+ counterion with the oxygen atoms of the guanine nucleobases and hence represents a photostable channel operative in natural nucleic acids.

6.
Front Chem ; 6: 495, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30386775

RESUMO

The adequate exploration of the phase space of a chromophore is a fundamental necessity for the simulation of their optical and photophysical properties, taking into account the effects of vibrational motion and, most importantly, the coupling with a (non-homogeneous) molecular environment. A representative set of conformational snapshots around the Franck-Condon region is also required to perform non-adiabatic molecular dynamics, for instance in the framework of surface hopping. Indeed, in the latter case one needs to prepare a set of initial conditions providing a meaningful and complete statistical base for the subsequent trajectory propagation. In this contribution, we propose two new protocols for molecular dynamics-based phase space sampling, called "local temperature adjustment" and "individual QM/MM-based relaxation." These protocols are intended for situations in which the popular Wigner distribution sampling procedure is not applicable-as it is the case when anharmonic or nonlinear vibrations are present-and where regular molecular dynamics sampling might suffer from an inaccurate distribution of internal energy or from inaccurate force fields. The new protocols are applied to the case of phase space sampling of [Re(CO)3(Im)(Phen)]+ (im, imidazole; phen, phenanthroline) in aqueous solution, showing the advantages and limitations of regular Wigner and molecular dynamics sampling as well as the strengths of the new protocols.

7.
Chemistry ; 24(54): 14425-14435, 2018 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-29949217

RESUMO

Optical properties of [Re(CO)3 (dppz)(py)]+ (dppz=dipyrido[3,2-a:2',3'-c]phenazine; py=pyridine) in acetonitrile, water and DNA have been investigated based on DFT, time-dependent-DFT (TD-DFT)/ conductor-like screening model, with and without explicit solvent molecules, and molecular dynamics. Whereas implicit solvent model is not appropriate to model optical properties of dppz-substituted metal complexes, adding explicit solvent molecules in interaction with dppz stabilizes the metal-to-ligand-charge-transfer (MLCT) transitions. Classical molecular dynamics simulations point to an important conformational flexibility, as evidenced by the coexistence of two conformers A and B. When considering the conformational sampling, the lowest band of the absorption spectrum is red-shifted and broadened up to 500 nm in agreement with the experimental spectra supporting important dynamical effects. The absorption spectra of [Re(CO)3 (dppz)(py-R)]+/ GC-DNA and [Re(CO)3 (dppz)(py-R)]+ /AT-DNA (R=CH2 -CH2 -COO- ) intercalated in both major or minor grooves exhibit a lowest energy charge separated (CS) band at about 600 nm and 500 nm, respectively, corresponding mainly to excitations from guanine and adenine to dppz. These states may play a central role into DNA-mediated charge transport processes. The over stabilization of the lowest 3 ILdppz state of [Re(CO)3 (dppz)(py)]+ in water as compared to acetonitrile could be responsible for the quenching of emission in water.


Assuntos
Complexos de Coordenação/química , DNA/química , Substâncias Intercalantes/química , Fenazinas/química , Rênio/química , Adenina/química , Guanina/química , Ligantes , Simulação de Dinâmica Molecular , Espectrofotometria
8.
Front Chem ; 6: 86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29666792

RESUMO

Bio-macromolecules as DNA, lipid membranes and (poly)peptides are essential compounds at the core of biological systems. The development of techniques and methodologies for their characterization is therefore necessary and of utmost interest, even though difficulties can be experienced due to their intrinsic complex nature. Among these methods, spectroscopies, relying on optical properties are especially important to determine their macromolecular structures and behaviors, as well as the possible interactions and reactivity with external dyes-often drugs or pollutants-that can (photo)sensitize the bio-macromolecule leading to eventual chemical modifications, thus damages. In this review, we will focus on the theoretical simulation of electronic spectroscopies of bio-macromolecules, considering their secondary structure and including their interaction with different kind of (photo)sensitizers. Namely, absorption, emission and electronic circular dichroism (CD) spectra are calculated and compared with the available experimental data. Non-linear properties will be also taken into account by two-photon absorption, a highly promising technique (i) to enhance absorption in the red and infra-red windows and (ii) to enhance spatial resolution. Methodologically, the implications of using implicit and explicit solvent, coupled to quantum and thermal samplings of the phase space, will be addressed. Especially, hybrid quantum mechanics/molecular mechanics (QM/MM) methods are explored for a comparison with solely QM methods, in order to address the necessity to consider an accurate description of environmental effects on spectroscopic properties of biological systems.

9.
Molecules ; 23(2)2018 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29370096

RESUMO

DNA is the target of chemical compounds (drugs, pollutants, photosensitizers, etc.), which bind through non-covalent interactions. Depending on their structure and their chemical properties, DNA binders can associate to the minor or to the major groove of double-stranded DNA. They can also intercalate between two adjacent base pairs, or even replace one or two base pairs within the DNA double helix. The subsequent biological effects are strongly dependent on the architecture of the binding motif. Discriminating between the different binding patterns is of paramount importance to predict and rationalize the effect of a given compound on DNA. The structural characterization of DNA complexes remains, however, cumbersome at the experimental level. In this contribution, we employed all-atom molecular dynamics simulations to determine the standard binding free energy of DNA with netropsin, a well-characterized antiviral and antimicrobial drug, which associates to the minor groove of double-stranded DNA. To overcome the sampling limitations of classical molecular dynamics simulations, which cannot capture the large change in configurational entropy that accompanies binding, we resort to a series of potentials of mean force calculations involving a set of geometrical restraints acting on collective variables.


Assuntos
DNA/química , Modelos Moleculares , Netropsina/química , Conformação de Ácido Nucleico , Conformação Proteica , Algoritmos , Sítios de Ligação , DNA/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Netropsina/metabolismo , Relação Estrutura-Atividade
10.
Phys Chem Chem Phys ; 19(40): 27240-27250, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28984331

RESUMO

We present a quantum-chemical investigation of the excited states of the complex [Re(CO)3(Im)(Phen)]+ (Im = imidazole; Phen = 1,10-phenanthroline) in solution including spin-orbit couplings and vibrational sampling. To this aim, we implemented electrostatic embedding quantum mechanics/molecular mechanics (QM/MM) in the Amsterdam Density Functional program suite, suitable for time-dependent density functional calculations including spin-orbit couplings. The new implementation is employed to simulate the absorption spectrum of the complex, which is compared to the results of implicit continuum solvation and frozen-density embedding. Molecular dynamics simulations are used to sample the ground state conformations in solution. The results demonstrate that any study of the excited states of [Re(CO)3(Im)(Phen)]+ in solution and their dynamics should include extensive sampling of vibrational motion and spin-orbit couplings.

11.
Sci Rep ; 7(1): 8885, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28827702

RESUMO

Nonsteroidal 2-arylproprionic acids are widely used, over-the-counter, anti-inflammatory drugs. Photosensitivity is a commonly overlooked adverse effect of these drugs. Based on the combined use of cell viability assays and molecular modeling, we prove and rationalize the photochemical pathways triggering photosensitization for two drugs, ibuprofen and ketoprofen. As its parent compound benzophenone, ketoprofen produces singlet oxygen, upon triplet manifold population. However, ibuprofen and ketoprofen photodissociate and hence may generate two highly reactive radicals. The formation of metastable aggregates between the two drugs and B-DNA is also directly probed by molecular dynamics. Our approach characterizes the coupled influence of the drug's intrinsic photochemistry and the interaction pattern with DNA. The photosensitization activity of nonsteroidal 2-arylproprionic acids, being added to gels and creams for topical use, should be crucially analyzed and rationalized to enact the proper preventive measures.


Assuntos
Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Ibuprofeno/farmacologia , Cetoprofeno/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Raios Ultravioleta , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Ibuprofeno/química , Cetoprofeno/química , Modelos Moleculares , Estrutura Molecular , Fármacos Fotossensibilizantes/química , Relação Estrutura-Atividade , Raios Ultravioleta/efeitos adversos
12.
Phys Chem Chem Phys ; 19(34): 23187-23193, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28820528

RESUMO

Resorting to state-of-the art molecular modeling and simulation techniques we provide full characterization of the photophysical properties of the naturally occurring hypericin chromophore, currently used in photodynamic therapy. In particular, we reveal the different photophysical pathways leading to intersystem-crossing and hence, triplet manifold population that is necessary for the subsequent production of singlet oxygen. In particular we identify an extended region of quasi-degeneracy between the first singlet excited state and three triplet state surfaces. This energetic factor allows the occurrence of intersystem-crossing even in the presence of a relatively small spin-orbit coupling. Furthermore, thanks to extended all-atom molecular dynamics simulations we provide insight into the interaction of hypericin with lipid bilayers. We demonstrate the formation of stable interactions with the membrane and, in particular, the penetration of hypericin into its hydrophobic core. This organization allows a spatial overlap between hypericin and the lipid oxidizable double bond pointing towards the production of singlet oxygen in close spatial proximity to its reactant, hence favoring photosensitization.


Assuntos
Bicamadas Lipídicas/metabolismo , Perileno/análogos & derivados , Luz , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Perileno/química , Perileno/metabolismo , Teoria Quântica , Oxigênio Singlete/química
13.
J Phys Chem B ; 121(32): 7586-7592, 2017 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-28735538

RESUMO

We report a combined computational and experimental study to rationalize the behavior of a well-known singlet oxygen (1O2) probe, that is, the chromophore of the Singlet Oxygen Sensor Green: a fluoresceine-based sensor. In particular, we evidence that the presence of an intramoleculer charge transfer state that is no more present upon reaction with 1O2 explains the fluorescence enhancement observed in the presence of reactive oxygen species. Furthermore, we also unequivocally show the photophysical pathways leading to the fluorescence enhancement of fluoresceine upon irradiation with UVA lights and also in the absence of any oxygen activator. More specifically, we evidence that the presence of a possible intersystem crossing upon population of higher energy singlet electronic excited states will lead to the population of the fluoresceine triplet manifold and hence to the self-production of 1O2.

14.
J Chem Theory Comput ; 13(7): 3290-3296, 2017 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-28548847

RESUMO

Electronic circular dichroism (CD) spectroscopy of peptides is one of the most important experimental characterization tools to get insights regarding their structure. Nevertheless, even though highly useful, the reliable simulations of CD spectra result in a complex task. Here, we propose a combination of quantum mechanics/molecular mechanics (QM/MM) methods with a semiempirical Hamiltonian based on the Frenkel excitons theory to efficiently describe the behavior of a model 27-amino acid α-helical peptide in water. Especially, we show how the choice of the QM region, including different possible hydrogen-bonding patterns, can substantially change the final CD spectrum shape. Moreover, we prove that our approach can correctly explain the changes observed in the peptide conformation (from α-helix to α-hairpin) when covalently linked to a protonated retinal-like molecular switch and exposing the system to UVA light, as previously observed by experiment and extensive molecular dynamics. Hence our protocol may be straightforwardly exploited to characterize light-induced conformation changes in photoactive materials and more generally protein folding processes.


Assuntos
Dicroísmo Circular , Peptídeos/química , Ligações de Hidrogênio , Isomerismo , Modelos Moleculares , Peptídeos/metabolismo , Estrutura Secundária de Proteína , Teoria Quântica , Raios Ultravioleta , Água/química , Água/metabolismo
15.
Nucleic Acids Res ; 45(7): 3654-3662, 2017 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-28334906

RESUMO

DNA photolesions constitute a particularly deleterious class of molecular defects responsible for the insurgence of a vast majority of skin malignant tumors. Dimerization of two adjacent thymines or cytosines mostly gives rise to cyclobutane pyrimidine dimers (CPD) and pyrimidine(6-4)pyrimidone 64-PP as the most common defects. We perform all-atom classical simulations, up to 2 µs, of CPD and 64-PP embedded in a 16-bp duplex, which reveal the constrasted behavior of the two lesions. In particular we evidence a very limited structural deformation induced by CPD while 64-PP is characterized by a complex structural polymorphism. Our simulations also allow to unify the contrasting experimental structural results obtained by nuclear magnetic resonance or Förster Resonant Energy Transfer method, showing that both low and high bent structures are indeed accessible. These contrasting behaviors can also explain repair resistance or the different replication obstruction, and hence the genotoxicity of these two photolesions.


Assuntos
Reparo do DNA , Dímeros de Pirimidina/química , DNA de Forma B/química , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico
16.
Phys Chem Chem Phys ; 18(48): 33180-33186, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27892573

RESUMO

We report the investigation of the thermochemical properties of benzophenone interacting with B-DNA studied by all-atom molecular dynamic simulations. In particular, we determine the binding free energy for two competitive binding modes, minor groove binding and double insertion. Our results allow us to quantitatively resolve for the first time the mode of binding of this paradigmatic photosensitizer, indicating a marked preference for minor groove binding. Furthermore, we have settled a protocol allowing for the determination of binding energies in the case of non-covalent interaction with DNA, in particular, tackling the non-trivial problem of the strong reorganization of the DNA imposing extended statistical sampling. Our contribution paves the way to the systematic determination of the thermochemical properties of drugs or pollutants interacting with DNA.


Assuntos
Simulação por Computador , DNA de Forma B , Termodinâmica , Animais , Humanos , Substâncias Intercalantes , Modelos Moleculares , Conformação de Ácido Nucleico
17.
Nucleic Acids Res ; 44(18): 8588-8599, 2016 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-27587587

RESUMO

Clustered apurinic/apyrimidinic (AP; abasic) DNA lesions produced by ionizing radiation are by far more cytotoxic than isolated AP lesion entities. The structure and dynamics of a series of seven 23-bp oligonucleotides featuring simple bistranded clustered damage sites, comprising of two AP sites, zero, one, three or five bases 3' or 5' apart from each other, were investigated through 400 ns explicit solvent molecular dynamics simulations. They provide representative structures of synthetically engineered multiply damage sites-containing oligonucleotides whose repair was investigated experimentally (Nucl. Acids Res. 2004, 32:5609-5620; Nucl. Acids Res. 2002, 30: 2800-2808). The inspection of extrahelical positioning of the AP sites, bulge and non Watson-Crick hydrogen bonding corroborates the experimental measurements of repair efficiencies by bacterial or human AP endonucleases Nfo and APE1, respectively. This study provides unprecedented knowledge into the structure and dynamics of clustered abasic DNA lesions, notably rationalizing the non-symmetry with respect to 3' to 5' position. In addition, it provides strong mechanistic insights and basis for future studies on the effects of clustered DNA damage on the recognition and processing of these lesions by bacterial or human DNA repair enzymes specialized in the processing of such lesions.


Assuntos
Dano ao DNA , DNA/química , Conformação de Ácido Nucleico , Sequência de Bases , Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Humanos , Simulação de Dinâmica Molecular , Fatores de Tempo
18.
J Phys Chem Lett ; 7(19): 3760-3765, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27612215

RESUMO

In the present contribution, the interaction between damaged DNA and repair enzymes is examined by means of molecular dynamics simulations. More specifically, we consider clustered abasic DNA lesions processed by the primary human apurinic/apyrimidinic (AP) endonuclease, APE1. Our results show that, in stark contrast with the corresponding bacterial endonucleases, human APE1 imposes strong geometrical constraints on the DNA duplex. As a consequence, the level of recognition and, hence, the repair rate is higher. Important features that guide the DNA/protein interactions are the presence of an extended positively charged region and of a molecular tweezers that strongly constrains DNA. Our results are on very good agreement with the experimentally determined repair rate of clustered abasic lesions. The lack of repair for one particular arrangement of the two abasic sites is also explained considering the peculiar destabilizing interaction between the recognition region and the second lesion, resulting in a partial opening of the molecular tweezers and, thus, a less stable complex. This contribution cogently establishes the molecular bases for the recognition and repair of clustered DNA lesions by means of human endonucleases.


Assuntos
Reparo do DNA , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , DNA/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Sítios de Ligação , DNA/química , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/química , Humanos , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico , Estrutura Terciária de Proteína , Especificidade por Substrato
19.
Sci Rep ; 6: 28480, 2016 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-27329409

RESUMO

We report a molecular modeling study, coupled with spectroscopy experiments, on the behavior of two well known organic dyes, nile blue and nile red, when interacting with B-DNA. In particular, we evidence the presence of two competitive binding modes, for both drugs. However their subsequent photophysical behavior is different and only nile blue is able to induce DNA photosensitization via an electron transfer mechanism. Most notably, even in the case of nile blue, its sensitization capabilities strongly depend on the environment resulting in a single active binding mode: the minor groove. Fluorescence spectroscopy confirms the presence of competitive interaction modes for both sensitizers, while the sensitization via electron transfer, is possible only in the case of nile blue.


Assuntos
DNA de Forma B/química , Oxazinas/química , Fármacos Fotossensibilizantes/química , Sítios de Ligação , Ligação Competitiva , Simulação por Computador , Transporte de Elétrons , Corantes Fluorescentes/química , Modelos Moleculares , Conformação de Ácido Nucleico , Processos Fotoquímicos , Polidesoxirribonucleotídeos/química , Espectrometria de Fluorescência , Espectrofotometria
20.
Phys Chem Chem Phys ; 18(27): 18598-606, 2016 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-27345613

RESUMO

DNA photosensitization is one of the physical processes behind photodynamic therapy techniques, i.e. the combined use of photoactive drugs and visible radiation for therapeutical purposes. In this contribution we report the analysis of the photophysical properties of a two-photon absorption dye together with its interaction with DNA. The linear and non-linear optical properties are modeled taking into account the complex environment including dynamic and vibrational effects. It is also clearly demonstrated that the excited state manifold may evolve toward spontaneous photoionization with the production of a solvated electron. In turn both the radical cation and the solvated electron may react with the DNA backbone to produce a strand break; hence we have characterized a phototherapeutic dye that absorbs in the infrared region and is able to work under hypoxidic conditions, i.e. a prodrug of great interest for the potential treatment of solid tumors.


Assuntos
Cátions/química , DNA/química , Elétrons , Luz , Modelos Moleculares , Processos Fotoquímicos , Fótons , Fenômenos Físicos , Vibração
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