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1.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360798

RESUMO

Non-covalent interactions responsible for molecular features and self-assembly in Naphthazarin C polymorph were investigated on the basis of diverse theoretical approaches: Density Functional Theory (DFT), Diffusion Quantum Monte Carlo (DQMC), Symmetry-Adapted Perturbation Theory (SAPT) and Car-Parrinello Molecular Dynamics (CPMD). The proton reaction paths in the intramolecular hydrogen bridges were studied. Two potential energy minima were found indicating that the proton transfer phenomena occur in the electronic ground state. Diffusion Quantum Monte Carlo (DQMC) and other levels of theory including Coupled Cluster (CC) employment enabled an accurate inspection of Potential Energy Surface (PES) and revealed the energy barrier for the proton transfer. The structure and reactivity evolution associated with the proton transfer were investigated using Harmonic Oscillator Model of Aromaticity - HOMA index, Fukui functions and Atoms In Molecules (AIM) theory. The energy partitioning in the studied dimers was carried out based on Symmetry-Adapted Perturbation Theory (SAPT) indicating that dispersive forces are dominant in the structure stabilization. The CPMD simulations were performed at 60 K and 300 K in vacuo and in the crystalline phase. The temperature influence on the bridged protons dynamics was studied and showed that the proton transfer phenomena were not observed at 60 K, but the frequent events were noticed at 300 K in both studied phases. The spectroscopic signatures derived from the CPMD were computed using Fourier transformation of autocorrelation function of atomic velocity for the whole molecule and bridged protons. The computed gas-phase IR spectra showed two regions with OH absorption that covers frequencies from 2500 cm-1 to 2800 cm-1 at 60 K and from 2350 cm-1 to 3250 cm-1 at 300 K for both bridged protons. In comparison, the solid state computed IR spectra revealed the environmental influence on the vibrational features. For each of them absorption regions were found between 2700-3100 cm-1 and 2400-2850 cm-1 at 60 K and 2300-3300 cm-1 and 2300-3200 cm-1 at 300 K respectively. Therefore, the CPMD study results indicated that there is a cooperation of intramolecular hydrogen bonds in Naphthazarin molecule.


Assuntos
Simulação de Dinâmica Molecular , Naftoquinonas/química , Ligação de Hidrogênio , Teoria Quântica
2.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445657

RESUMO

In this paper, we present a formulation of highly correlated Fock-space multi-reference coupled-cluster (FSMRCC) methods, including approximate triples on top of the FSMRCC with singles and doubles, which correct the electron affinities by at least at third and up to the fourth order in perturbation. We discuss various partial fourth-order schemes, which are reliable and yet computationally more efficient than the full fourth-order triples scheme. The third-order scheme is called MRCCSD+T*(3). We present two approximate fourth-order schemes, MRCCSD+T*-a(4) and MRCCSD+T*(4). The results that are presented allow one to choose an appropriate fourth-order scheme, which is less expensive and right for the problem. All these schemes are based on the effective Hamiltonian scheme, and provide a direct calculation of the vertical electron affinities. We apply these schemes to a prototype Li2 molecule, using four different basis sets, as well as BeO and CH+. We have calculated the vertical electron affinities of Li2 at the geometry of the neutral Li2 molecule. We also present the vertical ionization potentials of the Li2 anion at the geometry of the anion ground state. We have also shown how to calculate adiabatic electron affinity, though in that case we lose the advantages of direct calculation. BeO has been examined in two basis sets. For CH+, four different basis sets have been used. We have presented the partial fourth-order schemes to the EA in all the basis sets. The results are analyzed to illustrate the importance of triples, as well as highlight computationally efficient partial fourth-order schemes. The choice of the basis set on the electron affinity calculation is also emphasized. Comparisons with available experimental and theoretical results are presented. The general fourth-order schemes, which are conceptually equivalent with the Fock-space multi-reference coupled-cluster singles, doubles, and triplets (MRCCSD+T) methods, based on bondonic formalism, are also presented here in a composed way, for quantum electronic affinity.


Assuntos
Algoritmos , Elétrons , Lítio/química , Modelos Químicos , Teoria Quântica , Fenômenos Físicos
3.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443556

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly infectious zoonotic virus first reported into the human population in September 2012 on the Arabian Peninsula. The virus causes severe and often lethal respiratory illness in humans with an unusually high fatality rate. The N-terminal domain (NTD) of receptor-binding S1 subunit of coronavirus spike (S) proteins can recognize a variety of host protein and mediates entry into human host cells. Blocking the entry by targeting the S1-NTD of the virus can facilitate the development of effective antiviral drug candidates against the pathogen. Therefore, the study has been designed to identify effective antiviral drug candidates against the MERS-CoV by targeting S1-NTD. Initially, a structure-based pharmacophore model (SBPM) to the active site (AS) cavity of the S1-NTD has been generated, followed by pharmacophore-based virtual screening of 11,295 natural compounds. Hits generated through the pharmacophore-based virtual screening have re-ranked by molecular docking and further evaluated through the ADMET properties. The compounds with the best ADME and toxicity properties have been retrieved, and a quantum mechanical (QM) based density-functional theory (DFT) has been performed to optimize the geometry of the selected compounds. Three optimized natural compounds, namely Taiwanhomoflavone B (Amb23604132), 2,3-Dihydrohinokiflavone (Amb23604659), and Sophoricoside (Amb1153724), have exhibited substantial docking energy >-9.00 kcal/mol, where analysis of frontier molecular orbital (FMO) theory found the low chemical reactivity correspondence to the bioactivity of the compounds. Molecular dynamics (MD) simulation confirmed the stability of the selected natural compound to the binding site of the protein. Additionally, molecular mechanics generalized born surface area (MM/GBSA) predicted the good value of binding free energies (ΔG bind) of the compounds to the desired protein. Convincingly, all the results support the potentiality of the selected compounds as natural antiviral candidates against the MERS-CoV S1-NTD.


Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Teoria Quântica , Antivirais/metabolismo , Produtos Biológicos/metabolismo , Domínio Catalítico , Avaliação Pré-Clínica de Medicamentos , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Interface Usuário-Computador
4.
Nature ; 596(7872): 348-349, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34408326

Assuntos
Teoria Quântica
5.
J Phys Chem Lett ; 12(34): 8263-8271, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34424693

RESUMO

The role of protonation states of the chromophore and its neighboring amino acid side chains of the reversibly switching fluorescent protein rsEGFP2 upon photoswitching is characterized by molecular modeling methods. Numerous conformations of the chromophore-binding site in computationally derived model systems are obtained using the quantum chemistry and QM/MM approaches. Excitation energies are computed using the extended multiconfigurational quasidegenerate perturbation theory (XMCQDPT2). The obtained structures and absorption spectra allow us to provide an interpretation of the observed structural and spectral properties of rsEGFP2 in the active ON and inactive OFF states. The results demonstrate that in addition to the dominating anionic and neutral forms of the chromophore, the cationic and zwitterionic forms may participate in the photoswitching of rsEGFP2. Conformations and protonation forms of the Glu223 and His149 side chains in the chromophore-binding site play an essential role in stabilizing specific protonation forms of the chromophore.


Assuntos
Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/metabolismo , Prótons , Teoria Quântica , Sítios de Ligação , Modelos Moleculares , Conformação Proteica
6.
J Phys Chem Lett ; 12(34): 8309-8313, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34428044

RESUMO

Guanine quadruplexes are four-stranded DNA/RNA structures composed of a guanine core (vertically stacked guanine tetrads) and peripheral groups (dangling ends and/or loops). Such a dual structural arrangement of the nucleobases favors their photoionization at energies significantly lower than the guanine ionization potential. This effect is important with respect to the oxidative DNA damage and for applications in the field of optoelectronics. Photoionization quantum yields, determined at 266 nm by nanosecond transient absorption spectroscopy, strongly depend on both the type and position of the peripheral nucleobases. The highest value (1.5 × 10-2) is found for the tetramolecular structure (AG4A)4 in which adenines are intermittently stacked on the adjacent guanine tetrads, as determined by nuclear magnetic resonance spectroscopy. Quantum chemistry calculations show that peripheral nucleobases interfere in a key step preceding electron ejection: charge separation, initiated by the population of charge transfer states during the relaxation of electronic excited states.


Assuntos
Quadruplex G , Guanina/química , Raios Ultravioleta , Modelos Moleculares , Teoria Quântica
7.
J Chem Phys ; 155(4): 044110, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34340364

RESUMO

A multi-level layered elongation method was developed for efficiently analyzing the electronic states of local structures in large bio/nano-systems at the full ab initio level of theory. The original elongation method developed during the last three decades in our group has focused on the system in one direction from one terminal to the other terminal to sequentially construct the electronic states of a polymer, called a theoretical synthesis of polymers. In this study, an important region termed the central (C) part is targeted in a large polymer and the remainder are terminal (T) parts. The electronic structures along with polymer elongation are calculated repeatedly from both end T parts to the C central part at the same time. The important C part is treated with large basis sets (high level) and the other regions are treated with small basis sets (low level) in the ab initio theoretical framework. The electronic structures besides the C part can be reused for other systems with different structures at the C part, which renders the method computationally efficient. This multi-level layered elongation method was applied to the investigation on DNA single bulge recognition of small molecules (ligands). The reliability and validity of our approach were examined in comparison with the results obtained by direct calculations using a conventional quantum chemical method for the entire system. Furthermore, stabilization energies by the formation of the complex of bulge DNA and a ligand were estimated with basis set superposition error corrections incorporated into the elongation method.


Assuntos
DNA/química , Conformação de Ácido Nucleico , Química Computacional , Descoberta de Drogas , Ligantes , Teoria Quântica
8.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361046

RESUMO

Ammonia is a well-known example of a two-state system and must be described in quantum-mechanical terms. In this article, we will explain the tunneling phenomenon that occurs in ammonia molecules from the perspective of trajectory-based quantum dynamics, rather than the usual quantum probability perspective. The tunneling of the nitrogen atom through the potential barrier in ammonia is not merely a probability problem; there are underlying reasons and mechanisms explaining why and how the tunneling in ammonia can happen. Under the framework of quantum Hamilton mechanics, the tunneling motion of the nitrogen atom in ammonia can be described deterministically in terms of the quantum trajectories of the nitrogen atom and the quantum forces applied. The vibrations of the nitrogen atom about its two equilibrium positions are analyzed in terms of its quantum trajectories, which are solved from the Hamilton equations of motion. The vibration periods are then computed by the quantum trajectories and compared with the experimental measurements.


Assuntos
Amônia/química , Simulação de Dinâmica Molecular , Teoria Quântica
9.
Sensors (Basel) ; 21(15)2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34372267

RESUMO

With the advent of the Industry 4.0 paradigm, the possibilities of controlling manufacturing processes through the information provided by a network of sensors connected to work centers have expanded. Real-time monitoring of each parameter makes it possible to determine whether the values yielded by the corresponding sensor are in their normal operating range. In the interplay of the multitude of parameters, deterministic analysis quickly becomes intractable and one enters the realm of "uncertain knowledge". Bayesian decision networks are a recognized tool to control the effects of conditional probabilities in such systems. However, determining whether a manufacturing process is out of range requires significant computation time for a decision network, thus delaying the triggering of a malfunction alarm. From its origins, JIDOKA was conceived as a means to provide mechanisms to facilitate real-time identification of malfunctions in any step of the process, so that the production line could be stopped, the cause of the disruption identified for resolution, and ultimately the number of defective parts minimized. Our hypothesis is that we can model the internal sensor network of a computer numerical control (CNC) machine with quantum simulations that show better performance than classical models based on decision networks. We show a successful test of our hypothesis by implementing a quantum digital twin that allows for the integration of quantum computing and Industry 4.0. This quantum digital twin simulates the intricate sensor network within a machine and permits, due to its high computational performance, to apply JIDOKA in real time within manufacturing processes.


Assuntos
Metodologias Computacionais , Teoria Quântica , Algoritmos , Teorema de Bayes , Simulação por Computador , Humanos
11.
J Phys Chem Lett ; 12(28): 6604-6612, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34251826

RESUMO

Xanthophylls are a class of oxygen-containing carotenoids, which play a fundamental role in light-harvesting pigment-protein complexes and in many photoresponsive proteins. The complexity of the manifold of the electronic states and the large sensitivity to the environment still prevent a clear and coherent interpretation of their photophysics and photochemistry. In this Letter, we compare cutting-edge ab initio methods (CC3 and DMRG/NEVPT2) with time-dependent DFT and semiempirical CI (SECI) on model keto-carotenoids and show that SECI represents the right compromise between accuracy and computational cost to be applied to real xanthophylls in their biological environment. As an example, we investigate canthaxanthin in the orange carotenoid protein and show that the conical intersections between excited states and excited-ground states are mostly determined by the effective bond length alternation coordinate, which is significantly tuned by the protein through geometrical constraints and electrostatic effects.


Assuntos
Modelos Moleculares , Xantofilas/química , Conformação Molecular , Teoria Quântica , Eletricidade Estática
12.
J Phys Chem Lett ; 12(28): 6744-6751, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34264091

RESUMO

The reaction of H atoms with glycine was investigated at 3.1 K in para-H2, a quantum-solid host. The reaction was followed by IR spectroscopy, with the spectral analysis aided by quantum chemical computations. Comparison of the experimental IR spectrum with computed anharmonic frequencies and intensities proved that, regardless of the reactant glycine conformation, Cα-glycyl radical is formed in an H-atom-abstraction process with great selectivity. The product of the second H-atom abstraction, iminoacetic acid, was also observed in a smaller amount. The Cα-glycyl radical is sensitive to UV light and decomposes to iminoacetic acid and H atom upon 280 nm radiation. Since the reactive radical center is located on the Cα-atom, it is suggested that natural α-amino acids can be formed from glycine via the Cα-glycyl radical by non-energetic mechanisms in the solid phase of the interstellar medium.


Assuntos
Glicina/química , Temperatura , Hidrogênio/química , Modelos Moleculares , Conformação Molecular , Processos Fotoquímicos , Teoria Quântica
13.
J Phys Chem Lett ; 12(30): 7312-7318, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34319743

RESUMO

A new mechanism for enhanced intersystem crossing in coupled three-spin systems consisting of a chromophore and an attached radical is proposed. It is shown that if the unpaired electron of the radical experiences spin-orbit coupling and different exchange interactions with the two unpaired electron spins of the chromophore, energy transfer from the chromophore to the radical can occur together with singlet-triplet intersystem crossing in the chromophore. The efficiency of this process increases dramatically when the electronic excitation of the radical is resonant with the S1-T1 energy gap of the chromophore. The types of systems in which this resonance could be achieved are discussed, and it is suggested that the mechanism could result in improved sensitization in near-IR emitting lanthanide dyes.


Assuntos
Corantes/química , Radicais Livres/química , Elétrons , Transferência de Energia , Teoria Quântica
14.
J Chem Theory Comput ; 17(8): 5369-5378, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34232642

RESUMO

The halogen bond (or X-bond) is a noncovalent interaction that is increasingly recognized as an important design tool for engineering protein-ligand interactions and controlling the structures of proteins and nucleic acids. In the past decade, there have been significant efforts to characterize the structure-energy relationships of this interaction in macromolecules. Progress in the computational modeling of X-bonds in biological molecules, however, has lagged behind these experimental studies, with most molecular mechanics/dynamics-based simulation methods not properly treating the properties of the X-bond. We had previously derived a force field for biological X-bonds (ffBXB) based on a set of potential energy functions that describe the anisotropic electrostatic and shape properties of halogens participating in X-bonds. Although fairly accurate for reproducing the energies within biomolecular systems, including X-bonds engineered into a DNA junction, the ffBXB with its seven variable parameters was considered to be too unwieldy for general applications. In the current study, we have generalized the ffBXB by reducing the number of variables to just one for each halogen type and show that this remaining electrostatic variable can be estimated for any new halogenated molecule through a standard restricted electrostatic potential calculation of atomic charges. In addition, we have generalized the ffBXB for both nucleic acids and proteins. As a proof of principle, we have parameterized this reduced and more general ffBXB against the AMBER force field. The resulting parameter set was shown to accurately recapitulate the quantum mechanical landscape and experimental interaction energies of X-bonds incorporated into DNA junction and T4 lysozyme model systems. Thus, this reduced and generalized ffBXB is more readily adaptable for incorporation into classical molecular mechanics/dynamics algorithms, including those commonly used to design inhibitors against therapeutic targets in medicinal chemistry and materials in biomolecular engineering.


Assuntos
Halogênios/química , DNA/química , DNA/metabolismo , Modelos Moleculares , Muramidase/química , Muramidase/metabolismo , Teoria Quântica , Eletricidade Estática , Termodinâmica
15.
Spectrochim Acta A Mol Biomol Spectrosc ; 263: 120223, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34329849

RESUMO

Linuron is a commonly used organic herbicide which is used in plant growth control. Due to its potential health concerns, the characterization and monitoring of linuron have been a subject of several studies. In this work, we employed nuclear magnetic resonance (NMR) and Raman spectroscopic techniques supported with the density functional theory (DFT) to investigate the conformational behavior and electronic aspects of linuron. The selective nuclear Overhauser effect (SelNOE) spectra confirmed that linuron exists predominantly in the anti configuration and is facilitated with a weak intramolecular hydrogen bonding between the acidic amide proton and oxygen of methoxy moiety. Quantum chemical results showed that the corresponding syn form of the molecule is 8.5 kcal/mol less stable. Further, the surface enhanced Raman scattering (SERS) technique using gold nanoparticles (AuNPs) was implemented as a potential spectroscopic protocol for the concentration monitoring of trace linuron. The Raman responses of four vibrational modes, namely CC stretching, CN stretching, N-H rocking and ring deformation, were successfully enhanced with an excellent linear concentration-intensity dependency. The aromatic CC stretching vibration at 1595 cm-1 in the Raman spectra has demonstrated the highest enhancement factor (6.5 × 104) and the lowest limit of detection (10-7 M). The interaction of linuron with the gold nanocluster was simulated by establishing a simple DFT model which predicted that the most pronounced binding with the gold atom takes place at the benzene ring.


Assuntos
Ouro , Nanopartículas Metálicas , Linurona , Espectroscopia de Ressonância Magnética , Teoria Quântica , Análise Espectral Raman , Vibração
16.
J Photochem Photobiol B ; 222: 112261, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34330081

RESUMO

It is crucial to develop nanocarrier systems to detect and treat drug-resistant micro tumors to prevent recurrence and/or metastasis of cancer. Due to their exceptional features such as biocompatibility, easy surface modification, serving as imaging and therapeutic agent, gold nanoparticles (AuNPs) draw attention as theranostic agents. It is beneficial to combine AuNPs with a second imaging and/or treatment modality such as photodynamic therapy (PDT). PDT is a non-mutagenic treatment approach in which photosensitizer is activated with light, generating reactive oxygen species and/or free radicals to destroy tumor cells. With the aim of developing "off-on" theranostic system, citrate stabilized spherical 13 nm AuNPs were densely coated with polyethylene glycol (PEG). To advance the theranostic feature of PEGylated AuNPs, they were further functionalized with FDA-Approved photosensitizer, Verteporfin (BPD-MA). Due to static quenching between BPD-MA and AuNPs as well as in between nearby BPD-MA molecules, the fluorescence of the ground state complex is quenched and the system is in "off" state. When BPD-MA molecules are cleaved from the AuNPs surface and diffuse away, fluorescence is recovered. Consequently, the system switches to the "on" state. Among the various mole ratios of BPD-MA carrying conjugates prepared, the most promising candidate was selected based on stability, quenching factor, and fluorescence recovery rate. The conjugate was further decorated with D-α-Tocopherol succinate (VitES) to increase the therapeutic efficacy of the theranostic agent via enhancing cellular uptake. Our results showed that it was possible to achieve as high as 80 times fluorescence quenching when the system was "off". As the system switched from "off" to "on" state, 51% of the fluorescence was recovered. When BPD-MA was immobilized on the PEGylated AuNPs, the phototoxic effect of BPD-MA increased twice against the MCF-7 cell line. Moreover, the developed system showed four times more phototoxicity than BPD-MA alone after it was decorated with VitES. Since the developed system is capable of dual imaging (computed tomography and fluorescence) and dual treatment (PDT and hyperthermia), it potentially offers superior imaging and therapy options for various types of in vitro/in vivo applications.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Nanomedicina Teranóstica , alfa-Tocoferol/química , Sobrevivência Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Nanopartículas Metálicas/toxicidade , Microscopia Confocal , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Teoria Quântica , Oxigênio Singlete/metabolismo , Espectrometria de Fluorescência , Verteporfina/química , Verteporfina/farmacologia
17.
Chemosphere ; 281: 130831, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34289597

RESUMO

The understanding of the photochemistry of antibiotic compounds is important because it gives the direct information on the possible environmental pollution caused by them. Due to their large size, the theoretical studies of their excited-state reactions are rather challenging. In current work, we combined the on-the-fly trajectory surface-hopping dynamics, conical-intersection optimizations and excited-state pathway calculations to study the photochemistry of the trans-isomer of nitrofurantoin, a widely-used drug to treat the urinary tract infections. The dynamics-then-pathway approach was taken. First the trajectory surface hopping dynamics at the state-averaged complete-active-space self-consistent-field (SA-CASSCF) level with small active space and small basis sets were run. Second, the minimum-energy conical-intersection optimizations were performed. Finally the excited pathways from the Frank-Condon region to different reaction channels were built at the multi-state multi-reference second-order perturbation (MS-CASPT2) level with large active space and large basis set. Several possible channels responsible for the photo-induced reaction mechanism of the trans-nitrofurantoin were obtained, including the cleavage of the NO bond of the NO2 moiety, the photoisomerization at the central CN bond, and other internal conversion channels. Our findings give some preliminary explanations on available experimental observations. It is also demonstrates that the current theoretical approach is a powerful tool to explore the excited-state reactions in the photochemistry of media-sized or large-sized drug compounds.


Assuntos
Nitrofurantoína , Teoria Quântica , Isomerismo , Modelos Teóricos , Fotoquímica
18.
Int J Mol Sci ; 22(14)2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34299296

RESUMO

In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3-9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.


Assuntos
Ânions/química , Ácido Cítrico/química , Ácido Oxaloacético/química , Ânions/metabolismo , Ácido Cítrico/metabolismo , Elétrons , Gases/química , Modelos Teóricos , Ácido Oxaloacético/metabolismo , Teoria Quântica
19.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199541

RESUMO

Quinone methide precursors 1a-e, with different alkyl linkers between the naphthol and the naphthalimide chromophore, were synthesized. Their photophysical properties and photochemical reactivity were investigated and connected with biological activity. Upon excitation of the naphthol, Förster resonance energy transfer (FRET) to the naphthalimide takes place and the quantum yields of fluorescence are low (ΦF ≈ 10-2). Due to FRET, photodehydration of naphthols to QMs takes place inefficiently (ΦR ≈ 10-5). However, the formation of QMs can also be initiated upon excitation of naphthalimide, the lower energy chromophore, in a process that involves photoinduced electron transfer (PET) from the naphthol to the naphthalimide. Fluorescence titrations revealed that 1a and 1e form complexes with ct-DNA with moderate association constants Ka ≈ 105-106 M-1, as well as with bovine serum albumin (BSA) Ka ≈ 105 M-1 (1:1 complex). The irradiation of the complex 1e@BSA resulted in the alkylation of the protein, probably via QM. The antiproliferative activity of 1a-e against two human cancer cell lines (H460 and MCF 7) was investigated with the cells kept in the dark or irradiated at 350 nm, whereupon cytotoxicity increased, particularly for 1e (>100 times). Although the enhancement of this activity upon UV irradiation has no imminent therapeutic application, the results presented have importance in the rational design of new generations of anticancer phototherapeutics that absorb visible light.


Assuntos
Antineoplásicos/farmacologia , Indolquinonas/síntese química , Naftalimidas/química , Naftóis/química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Transferência Ressonante de Energia de Fluorescência , Humanos , Indolquinonas/química , Indolquinonas/farmacologia , Células MCF-7 , Estrutura Molecular , Processos Fotoquímicos , Teoria Quântica
20.
Inorg Chem ; 60(15): 11672-11683, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34269564

RESUMO

New neutral iridium(III) complexes featuring a cubic polyhedral oligomeric silsesquioxane (POSS) unit, [Ir(N∧C)2(L1-POSS)] [HN∧C = 2-phenylpyridine (Hppy; 1), 2-phenylbenzothioazole (Hbt; 2), and 2-(1-naphthyl)benzothiazole (Hbsn; 3); L1-POSS = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-heptakis(isobutyl)POSS-propyl carbamate], were designed and synthesized. Their POSS-free counterparts, [Ir(N∧C)2(L1)] [L1 = (E)-N-(4-hydroxymethylphenyl)-1-(2-hydroxyphenyl)methanimine; HN∧C = Hppy (1a), Hbt (2a), and Hbsn (3a)], and the poly(ethylene glycol) (PEG) derivatives [Ir(N∧C)2(L1-PEG)] [L1-PEG = (E)-4-[(2-hydroxybenzylidene)amino]benzyl 3-[2-[ω-methoxypoly(1-oxapropyl)]ethyl]carbamate; HN∧C = Hppy (1b), Hbt (2b), and Hbsn (3b)] were also prepared. The photophysical, photochemical, and biological properties of the POSS complexes were compared with those of their POSS-free and PEG-modified counterparts. Upon irradiation, all of these complexes displayed orange-to-red emission and long emission lifetimes under ambient conditions. The bsn complexes 3, 3a, and 3b exhibited the highest singlet oxygen (1O2) generation quantum yields (ΦΔ = 0.85-0.86) in aerated CH3CN. Laser-scanning confocal microscopy images revealed that complexes 1-3 and 1a-3a showed exclusive lipid-droplet staining upon cellular uptake, while the PEG derivatives 1b-3b displayed lysosomal localization. Complex 3 was utilized to study various lipid-droplet-related biological events including lipid-droplet accumulation under oleic acid stimulation, the movement of lipid droplets, and preadipocyte differentiation. Notably, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays indicated that the ppy complexes 1 and 1b and the bt complexes 2 and 2b were noncytotoxic both in the dark and upon irradiation at 450 nm for 5 min (IC50 > 200 µM), while the bsn complexes 3, 3a, and 3b showed low dark cytotoxicity (IC50 = 52.9 to >200 µM) and high photocytotoxicity (IC50 = 1.1-5.3 µM). The cellular uptake, internalization mechanisms, and cell death pathways of these complexes were also investigated. This work not only offers promising luminescent probes for lipid droplets through the structural modification of iridium(III) complexes but also paves the way to the construction of new reagents for theranostics.


Assuntos
Irídio/química , Gotículas Lipídicas/metabolismo , Substâncias Luminescentes/química , Imagem Molecular/métodos , Compostos de Organossilício/química , Células HeLa , Humanos , Processos Fotoquímicos , Polietilenoglicóis/química , Teoria Quântica
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