Insights into Halogen-Induced Changes in 4-Anilinoquinazoline EGFR Inhibitors: A Computational Spectroscopic Study.

The epidermal growth factor receptor (EGFR) is a pivotal target in cancer therapy due to its significance within the tyrosine kinase family. EGFR inhibitors like AG-1478 and PD153035, featuring a 4-anilinoquinazoline moiety, have garnered global attention for their potent therapeutic activities. While pre-clinical studies have highlighted the significant impact of halogen substitution at the C3'-anilino position on drug potency, the underlying mechanism remains unclear. This study investigates the influence of halogen substitution (X = H, F, Cl, Br, I) on the structure, properties, and spectroscopy of halogen-substituted 4-anilinoquinazoline tyrosine kinase inhibitors (TKIs) using time-dependent density functional methods (TD-DFT) with the B3LYP functional. Our calculations revealed that halogen substitution did not induce significant changes in the three-dimensional conformation of the TKIs but led to noticeable alterations in electronic properties, such as dipole moment and spatial extent, impacting interactions at the EGFR binding site. The UV-visible spectra show that more potent TKI-X compounds typically have shorter wavelengths, with bromine's peak wavelength at 326.71 nm and hydrogen, with the lowest IC50 nM, shifting its lambda max to 333.17 nm, indicating a correlation between potency and spectral characteristics. Further analysis of the four lowest-lying conformers of each TKI-X, along with their crystal structures from the EGFR database, confirms that the most potent conformer is often not the global minimum structure but one of the low-lying conformers. The more potent TKI-Cl and TKI-Br exhibit larger deviations (RMSD > 0.65 Å) from their global minimum structures compared to other TKI-X (RMSD < 0.15 Å), indicating that potency is associated with greater flexibility. Dipole moments of TKI-X correlate with drug potency (ln(IC50 nM)), with TKI-Cl and TKI-Br showing significantly higher dipole moments (>8.0 Debye) in both their global minimum and crystal structures. Additionally, optical spectral shifts correlate with potency, as TKI-Cl and TKI-Br exhibit blue shifts from their global minimum structures, in contrast to other TKI-X. This suggests that optical reporting can effectively probe drug potency and conformation changes.

Excited-State Proton Transfer in Luminescent Dyes: From Theoretical Insight to Experimental Evidence.

The effective utilization of luminescent dyes often relies on a comprehensive understanding of their excitation and relaxation pathways. One such pathway, Excited-State Proton Transfer (ESPT), involves the tautomerization of the dye in its excited state, resulting in a new structure that exhibits distinct emission properties, such as a very large Stokes' shift or dual-emission. Although the ESPT phenomenon is well-explained theoretically, its experimental demonstration can be challenging due to the presence of numerous other phenomena that can yield similar experimental observations. In this review, we propose that an all-encompassing methodology, integrating experimental findings, computational analyses, and a thorough evaluation of diverse mechanisms, is essential for verifying the occurrence of ESPT in luminescent dyes. Investigations have offered significant understanding of the elements impacting the ESPT process and the array of approaches that can be used to validate the existence of ESPT. These discoveries hold crucial ramifications for the advancement of molecular probes, sensors, and other applications that depend on ESPT as a detection mechanism.

1,2,4-Triazine-based Materials: Spectroscopic Investigation, DFT, NBO, and TD-DFT Calculations as Well As Dye-sensitized Solar Cells Applications.

In this manuscript, we report four series for 1,2,4-triazine derivatives as dye-sensitized solar cells (DSSCs). Density functional theory (DFT) methods via utilizing Becke's three-parameter functional and LeeeYangeParr functional (B3LYP) level with 6-31G (d, p) basis set to investigate their modeling molecular structures. Optimized molecular structures for studied molecular structures are obtained using the DFT/B3LYP/6-31G (d, p) method. In addition, the time-dependant density functional theory (TD-DFT) is used to study the optoelectronic properties and absorption spectra using DFT/CAM-B3LYP/ 6-31G + + (d, p) level in the Gaussian 09 program. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), energy gap (Eg), light harvest efficiency (LHE), and open-circuit voltage (Voc) of the studied molecular structures are calculated and illustrated. These properties indicate that these molecular modeling structures as good candidates for utilization in organic DSSCs.

Application of TD-DFT Theory to Studying Porphyrinoid-Based Photosensitizers for Photodynamic Therapy: A Review.

An important focus for innovation in photodynamic therapy (PDT) is theoretical investigations. They employ mostly methods based on Time-Dependent Density Functional Theory (TD-DFT) to study the photochemical properties of photosensitizers. In the current article we review the existing state-of-the-art TD-DFT methods (and beyond) which are employed to study the properties of porphyrinoid-based systems. The review is organized in such a way that each paragraph is devoted to a separate aspect of the PDT mechanism, e.g., correct prediction of the absorption spectra, determination of the singlet-triplet intersystem crossing, and interaction with molecular oxygen. Aspects of the calculation schemes are discussed, such as the choice of the most suitable functional and inclusion of a solvent. Finally, quantitative structure-activity relationship (QSAR) methods used to explore the photochemistry of porphyrinoid-based systems are discussed.

Enhancing the Viscosity-Sensitive Range of a BODIPY Molecular Rotor by Two Orders of Magnitude.

Molecular rotors are a class of fluorophores that enable convenient imaging of viscosity inside microscopic samples such as lipid vesicles or live cells. Currently, rotor compounds containing a boron-dipyrromethene (BODIPY) group are among the most promising viscosity probes. In this work, it is reported that by adding heavy-electron-withdrawing -NO2 groups, the viscosity-sensitive range of a BODIPY probe is drastically expanded from 5-1500 cP to 0.5-50 000 cP. The improved range makes it, to our knowledge, the first hydrophobic molecular rotor applicable not only at moderate viscosities but also for viscosity measurements in highly viscous samples. Furthermore, the photophysical mechanism of the BODIPY molecular rotors under study has been determined by performing quantum chemical calculations and transient absorption experiments. This mechanism demonstrates how BODIPY molecular rotors work in general, why the -NO2 group causes such an improvement, and why BODIPY molecular rotors suffer from undesirable sensitivity to temperature. Overall, besides reporting a viscosity probe with remarkable properties, the results obtained expand the general understanding of molecular rotors and show a way to use the knowledge of their molecular action mechanism for augmenting their viscosity-sensing properties.

Quantum Chemical Design Guidelines for Absorption and Emission Color Tuning of fac-Ir(ppy)3 Complexes.

The fac-Ir(ppy)3 complex, where ppy denotes 2-phenylpyridine, is one of the well-known luminescent metal complexes having a high quantum yield. However, there have been no specific molecular design guidelines for color tuning. For example, it is still unclear how its optical properties are changed when changing substitution groups of ligands. Therefore, in this study, differences in the electronic structures and optical properties among several substituted fac-Ir(ppy)3 derivatives are examined in detail by density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. On the basis of those results, we present rational design guidelines for absorption and emission color tuning by modifying the species of substituents and their substitution positions.

Theoretical Electronic Circular Dichroism Study of 1,3-Diene Derivatives for the Elucidation of ECD Spectra of 1,3-Cyclohexadiene and Its Derivatives.

The origin of P- or M-chirality of methyl substituted 1,3-cyclohexadienes are elucidated by time-dependent density functional theory (TD-DFT) calculation of 1,3-cyclohexadiene derivatives and acyclic 1,3-dienes. The sign-inversion of the rotatory strength of the lowest excited state between 1,3-cyclohexadiene and (5R)-axial-methyl-1,3-cyclohexadiene is caused by the conformation around the (C=)C-C(-Me) dihedral angle. The correlation between the sign of the rotatory strength and conformation has been found not only in methyl substituted derivatives but also fluoro substituted compounds.

A density functional theory study on the adsorption of Mercaptopurine anti-cancer drug and Cu/Zn-doped boron nitride nanocages as a drug delivery.

Targeted drug delivery along with the most negligible side effects, is the most important challenge in the designing of the novel anti-cancer drug delivery. Therefore, the interaction of Cu/Zn-doped boron nitride nanocages as the carrier for Mercaptopurine (MP) anti-cancer drug was studied by density functional theory calculations to design a novel carrier. The adsorption of MP drug on Cu/Zn-doped boron nitride nanocages is suitable energetically. In this study, electronic parameters and Gibbs free energy of complexes of Cu/Zn-doped boron nitride nanocages with two configuration MP drug (N and S) were investigated. In addition, CuBN has a short recovery time, but ZnBN has more selectivity for MP drug. It is predicted that the MP drug over both Cu/Zn-doped boron nitride nanocages can be used as a suitable drug delivery system. Configuration -S of MP drug in both nanocage is more appropriate than configuration -N. Analysis of frontier molecular orbitals, UV-VIS spectra and density of states plots of the designed complexes confirmed adsorption MP drug on Cu/Zn-doped boron nitride nanocages. This research predicted which Cu/Zn-doped boron nitride nanocages can be used as acceptable carriers for MP anti-cancer drug.Communicated by Ramaswamy H. Sarma.

Electron transfer-mediated synergistic nonlinear optical response in the Agn@C18 (n = 4-6) complexes: A DFT study on the electronic structures and optical characteristics.

Seeking highly efficient and stable non-linear optical (NLO) materials is crucial yet challenging, given their promising applications in laser diodes and photovoltaics. In this study, we employ the excess electron and charge transfer strategies to theoretically design three novel complexes, namely Agn@C18 (n = 4-6), by adsorbing silver clusters onto the cyclo[18]carbon ring (C18). Our aim is to investigate the NLO characteristics of these complexes using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The results reveal that the adsorption of Ag clusters onto C18 leads to a decrease in excitation energy and an increase in dipole moment and oscillator strengths, thereby significantly enhancing the hyperpolarizability of the complexes. Strikingly, among all these complexes, Ag6@C18 exhibits the highest first hyperpolarizability value of approximately 109496.2620 au calculated at the B3LYP/cc-PVDZ-pp level of theory, which is about 1.3 × 106 times higher than that of pure C18. This finding validates the effectiveness of the proposed strategies in enhancing the NLO response of the species. Moreover, the calculated UV-Vis absorption spectrum demonstrates that the Agn@C18 complexes with excess electrons exhibit absorption at longer wavelengths (ranging from 385 to 731 nm) compared to C18. In addition, the stability, chemical bonding, and charge transfer characteristics of the Agn@C18 (n = 4-6) complexes were also discussed. These findings highlight the potential of these complexes for the development of highly efficient NLO devices.

Multicomponent synthesis and photophysical study of novel α,ß-unsaturated carbonyl depsipeptides and peptoids.

Multicomponent reactions were performed to develop novel α,ß-unsaturated carbonyl depsipeptides and peptoids incorporating various chromophores such as cinnamic, coumarin, and quinolines. Thus, through the Passerini and Ugi multicomponent reactions (P-3CR and U-4CR), we obtained thirteen depsipeptides and peptoids in moderate to high yield following the established protocol and fundamentally varying the electron-rich carboxylic acid as reactants. UV/Vis spectroscopy was utilized to study the photophysical properties of the newly synthesized compounds. Differences between the carbonyl-substituted chromophores cause differences in electron delocalization that can be captured in the spectra. The near UV regions of all the compounds exhibited strong absorption bands. Compounds P2, P5, U2, U5, and U7 displayed absorption bands in the range of 250-350 nm, absorbing radiation in this broad region of the electromagnetic spectrum. A photostability study for U5 showed that its molecular structure does not change after exposure to UV radiation. Fluorescence analysis showed an incipient emission of U5, while U6 showed blue fluorescence under UV radiation. The photophysical properties and electronic structure were also determined by TD-DFT theoretical study.

Benchmarking DFT functionals for photophysics of pyranoflavylium cations.

An intense absorption, phosphorescence, a long triplet excited state lifetime and singlet oxygen generation capabilities are characteristics of pyranoflavylium cations, analogues to pyranoanthocyanidins originated in the maturation process of red wine. Such properties make these compounds potential photosensitizers to be applied in photodynamic therapy. In this context, the photophysical processes underlying that treatment critically depend on the electronic structure of the pyranoflavylium molecules. When employing density functional theory to describe the electronic structure of molecules, the choice of the most suitable functional is not trivial, and benchmark studies are needed to orient practitioners in the field. In this work, a benchmark of seven of the most commonly used density functionals in addressing the photophysical properties of a set of eight pyranoflavylium cations is reported. Ground and excited state geometries, molecular orbitals, and absorption, fluorescence and phosphorescence transition energies were calculated using density functional theory approaches, and evaluated and compared to experimental data and monoreferential wave function-based methodologies. Statistical analysis of the results indicates that global-hybrid functionals allow an excellent description of absorption and emission energies, with errors around 0.05 eV, while range-separated variants led to somewhat larger errors in the range 0.1-0.2 eV. In contrast, range-separated functionals display excellent phosphorescence energies with errors close to 0.05 eV, in this case global-hybrids showing increased discrepancies around 0.5-0.1 eV.

Near and vacuum UV polarization spectroscopy of 1,4-distyrylbenzene.

The UV absorbance bands of 1,4-distyrylbenzene (1,4-Bis[(E)-2-phenylethenyl]benzene, DSB) are investigated by Synchrotron Radiation Linear Dichroism (SRLD) spectroscopy using stretched polyethylene as an anisotropic solvent. The observed polarization data provide information on the transition moment directions of the observed spectral features. The investigation covers the range 15,000-58,000 cm-1 (667-172 nm), thereby providing new information on the transitions of DSB in the vacuum UV region. The observed spectrum is characterized by four main band systems centered at 27,600, 41,000, 49,800, and 57,500 cm-1 (362, 244, 201, and 174 nm). In general, the observed bands and their polarization directions are well predicted by the results of quantum chemical calculations using Time-Dependent Density Functional Theory (TD-DFT) with the functional CAM-B3LYP, and with the semiempirical all-valence-electrons method LCOAO.

Robust design of D-π-A model compounds using digital structures for organic DSSC applications.

New D-π-spacer-A model compound dye sensitizers (or dyes) are developed using digital structures for organic dyes sensitized solar cells (DSSCs) applications. Based on our previous studies, the model D-π-spacer-A dyes contain building blocks of a di(p-carboxy)-phenylamine as the electron donor and a perylene monoimide as the electron acceptor. The new D-π-spacer-A dyes are constructed through variations of a set of three model π-spacer units, fluorene, 3,4-ethylenedioxythiophene and thiophene. The new dyes are presented by digital structures of π(ijk) in a digital control Π-matrix. If the chromophore database of the π-units is arranged in a defined manner, the new dyes are therefore designed through selecting of the set of three integers (ijk). Properties such as the UV-vis spectra which are calculated using the time-dependent density functional theory (TD-DFT) determine if the new compounds are suitable for organic solar cell purposes. The same strategy can be applied to donors and acceptors in the D-π-spacer-A model compound in order to robust design and build new organic dyes for DSSCs. The digital structures of the organic compounds enhance the machine driven structure-property relationship establishment once the database is sufficiently comprehensive. The present study demonstrates that new compounds obtained through mixing the π-spacer units of fluorene, 3,4-ethylenedioxythiophene and thiophene, e.g. π121 and π211, result in better dyes in DSSC applications. The concise digital structures of the new dyes are able to achieve a more robust design of the organic dyes and other materials.

Resonance Raman spectroscopic and density functional theoretical study on microsolvated 2-Thiocytosine clusters with polar solvents.

Microsolvation effects on the excited state deactivation dynamics of 2-thiocytosine (2tC) were studied in hydrogen-bonded 2tC clusters with protic solvents using resonance Raman, FT-IR, FT-Raman, UV-vis spectroscopy combining with density functional theoretical calculation. Two protic solvents, water (H2O) and methanol (MeOH), and one aprotic solvent, acetonitrile (MeCN), were used to investigate the 2tC(H2O)1-5, 2tC(MeOH)1-5, and 2tC(MeCN)1-3 microsolvated clusters. In CH3OH and H2O solvents, most of the Raman shifts were due to the vibration modes of 2tC(solvent)n (solvent = H2O, CH3OH; n = 1-4) clusters via intermolecular NH⋯O hydrogen bonds (HB). The intermolecular >NH⋯O hydrogen bond interactions, which are the key constituents of stable thione structure of 2tC, revealed the spectra difference of 2tC in CH3CN, CH3OH and H2O. With the aid of electronic structural and vibration frequency calculations, the observed Raman spectra were assigned to the low energy isomers of 2tC(solvent)2 (solvent = H2O, CH3OH) clusters in water and methanol and 2tC(CH3CN) in acetonitrile solvents. 2tC(solvent)2 clusters in water and methanol may prohibit or promote excited state proton transfer reaction from sulfur atom to neighbor nitrogen atom due to the hydrogen bonding chain between 2tC and protic solvent molecules. Our experimental and theoretical studies confirmed that the hydrogen bond sites were located on the specified functional group SCNH of 2tC with solvent molecules.

Photoinduced degradation of indigo carmine: insights from a computational investigation.

In this work, we present a computational investigation on the photoexcitation of indigo carmine (IC). Physical insights regarding IC photoexcitation and photolysis were obtained from a fundamental perspective through quantum chemistry computations. Density functional theory (DFT) was used to investigate the ground state while its time-dependent formalism (TD-DFT) was used for probing excited state properties, such as vertical excitation energies, generalized oscillator strengths (GOS), and structures. All the computations were undertaken using two different approaches: M06-2X/6-311+G(d,p) and CAM-B3LYP/6-311+G(d,p), in water. Results determined using both methods are in systematic agreement. For instance, the first singlet excited state was found at 2.28 eV (with GOS = 0.4730) and 2.19 eV (GOS = 0.4695) at the TD-DFT/CAM-B3LYP/6-311+G(d,p) and TD-DFT/M06-2X/6-311+G(d,p) levels of theory, respectively. Excellent agreement was observed between the computed and the corresponding experimental UV-Vis spectra. Moreover, results suggest IC undergoes photodecomposition through excited state chemical reaction rather than via a direct photolysis path. To the best of our knowledge, this work is the first to tackle the photoexcitation, and its potential connections to photodegradation, of IC from a fundamental chemical perspective, being presented with expectations to motivate further studies.

DFT/TD-DFT study of novel T shaped phenothiazine-based organic dyes for dye-sensitized solar cells applications.

Five novel T shaped phenothiazine-based organic dyes DTTP1~5 with different spacers at N (10) position were designed. The geometries, electronic structures, absorption spectra, electron transfer and injection properties of these isolated dyes and dye/(TiO2)9 systems were investigated via density functional theory (DFT) and time dependent density functional theory (TD-DFT) calculation. The optimized geometries indicate that these T shaped dyes show non-planar conformations, which are helpful in suppressing the close intermolecular π-π aggregation in device and enhancing thermal stability. The calculated results indicate that type of π-conjugated spacers can affect the molecular absorption spectra. Introduction of thiophene-benzothiadizole-thiophene unit as π-conjugated spacer can most effectively shift the light absorption to near infrared region and enhance the light harvesting efficiency (LHE). Moreover, it is found that these dyes show a good performance of electron injection and dye regeneration owing to the proper electron injection driving force (ΔGinject) and dye regeneration driving force (ΔGreg). The theoretical results reveal that these dyes could be used as potential sensitizers for DSSCs, and DTTP4 would be the most plausible sensitizer for high-efficiency DSSCs due to the narrow HOMO-LUMO energy gap (ΔH-L), broad absorption spectrum, high LHE value, and large dipole moment (µnormal).

Theoretical investigation of phenothiazine-triphenylamine-based organic dyes with different π spacers for dye-sensitized solar cells.

Three phenothiazine-triphenylamine-based organic dyes (CD-1, CD-2 and CD-3) are designed based on the dye WD-8. The geometries, electronic structures, and electronic absorption spectra of these dyes before and after binding to TiO2 are studied by density functional theory (DFT) and time-dependent density functional theory (TD-DFT). The calculated geometries indicate that these dyes show good steric hindrance effect which is advantage to inhibit the close intermolecular π-π aggregation effectively. The lowest unoccupied molecular orbital (LUMO) and highest occupied molecular orbital (HOMO) energy levels of these dyes could ensure positive effect on the process of electron injection and dye regeneration. The simulated spectra of CD-1∼3 show better absorption than that of WD-8 in the low energy zone. All the calculated results demonstrate that these dyes could be used as potential sensitizers for DSSCs and show better performances than WD-8.

Modelagem Molecular (TD-DFT) aplicada na predição do fator de proteção solar de compostos naturais / Molecular Modeling (TD-DFT) applied to predict the sun protection factor of natural compounds

Na área da saúde pública, as doenças provocadas pela radiação solar têm ganho grande destaque, por serem cada vez mais comuns. Dentre as principais formas de prevenção a utilização de filtros solares são as mais comuns e de fácil acesso. Os filtros utilizados atuam por sua capacidade de refletir, absorver ou dispersar os raios solares ultravioletas (UV). A aplicação de métodos teóricos tornou-se indispensável no auxílio do planejamento de novos compostos com função terapêutica, em estudos de suas diferentes propriedades, buscando gerar, manipular e analisar representações realistas de estruturas moleculares obtidas a partir de cálculos de propriedades físico-químicas por meio da química computacional. Neste estudo, foram selecionados compostos naturais de origem vegetal (3-O-metilquercetina, ácido gálico, aloína, catequina, quercetina e resveratrol), os quais são descritos com propriedades fotoprotetoras, para os quais se aplicou métodos computacionais para predição dos espectros de absorção, por meio do método TD-DFT (Teoria funcional da densidade dependente do tempo). Foram avaliadas as principais transições eletrônicas dos compostos estudados e se as diferenças de energia HOMO e LUMO para os compostos que absorvem na faixa UV compreendem na UVA (320400 nm, 3.103.87 eV), UVB (290320 nm, 3.874.27 eV) ou na UVC (100290 nm, 4.2712.4 eV). Realizou-se a validação experimental para o método aplicado para o EMC, quercetina e resveratrol, demonstrando a eficácia. Após os estudos realizados concluímos que o resveratrol, teoricamente é um ótimo candidato a fotoprotetor. O estudo ofereceu informações relevantes sobre o poder de predição in silico para fotoprotetores, e se utilizado pode contribuir diminuindo de tempo e custos em pesquisas para desenvolver fármacos

In the area of public health, diseases caused by solar radiation have gained great prominence, as they are increasingly common. Among the main ways to prevent the use of sunscreens are the most common and easily accessible. The filters used act by their ability to reflect, absorb or scatter the sun's ultraviolet (UV) rays. The application of theoretical methods has become indispensable in helping to plan new compounds with therapeutic function, in studies of their different properties, seeking to generate, manipulate and analyze realistic representations of molecular structures obtained from calculations of physicochemical properties through computational chemistry. In this study, natural compounds of plant origin (3-O-methylquercetin, gallic acid, aloin, catechin, quercetin, and resveratrol) were selected, which are described with photoprotective properties, for which computational methods were applied to predict the absorption spectra, using the TD-DFT (Time-Dependent Density Functional Theory) method. The main electronic transitions of the studied compounds were evaluated and whether the differences in HOMO and LUMO energy for compounds that absorb in the UV range comprise UVA (320400 nm, 3.103.87 eV), UVB (290 320 nm, 3.87 4.27 eV) or UVC (100290 nm, 4.2712.4 eV). Experimental validation was carried out for the method applied for CME, quercetin, and resveratrol, demonstrating its effectiveness. After the studies carried out, we concluded that resveratrol, theoretically, is an excellent candidate for sunscreen. The study provided relevant information about the in silico predictive power for photoprotectors, and if used, it can contribute to reducing time and costs in research to develop drugs