Computational Study on the Mechanism of the Photouncaging Reaction of Vemurafenib: Toward an Enhanced Photoprotection Approach for Photosensitive Drugs

The photochemical behavior of the photosensitive first-line anticancer drug vemurafenib (VFB) is of great interest due to the impact of such behavior on its pharmacological activity. In this work, we computationally elucidated the mechanism of the photoinduced release of VFB from the 4,5-dimethoxy-2-nitrobenzene (DMNB) photoprotecting group by employing various density functional theory (DFT)/time-dependent DFT (TD-DFT) approaches. The computational investigations included a comparative assessment of the influence of the position of the photoprotecting group as a substituent on the thermodynamics and kinetics of the photouncaging reactions of two VFB-DMNB prodrugs, namely pyrrole (NP) and sulfonamide (NS). With the aid of the DFT calculations concerning the activation energy barrier (∆G‡), the obtained results suggest that the step of the photoinduced intramolecular proton transfer of the DMNB moiety is not detrimental concerning the overall reaction profile of the photouncaging reaction of both prodrugs. However, the obtained results suggested that the position of the substitution position of the DMNB photoprotecting group within the prodrug structure has a substantial impact on the photouncaging reaction. In particular, the DMNB-Ns-VFB prodrug exhibited a notable increase in ∆G‡ for the key step of ring opining within the DMNB moiety indicative of potentially hindered kinetics of the photouncaging process compared with DMNB-Np-VFB. Such an increase in ∆G‡ may be attributed to the electronic influence of the NP fragment of the prodrug. The results reported herein elaborate on the mechanism of the photoinduced release of an important anticancer drug from photoprotecting groups with the aim of enhancing our understanding of the photochemical behavior of such photosensitive pharmaceutical materials at the molecular level.

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The impact of cation–π, anion–π, and CH–π interactions on the excited-state intramolecular proton transfer of 1,4-dihydroxyanthraquinone

Molecular Systems Design & Engineering ◽

10.1039/d0me00088d ◽

2021 ◽

Author(s):

Asiyeh Shahraki ◽

Ali Ebrahimi ◽

Shiva Rezazadeh ◽

Roya Behazin

Keyword(s):

Density Functional Theory ◽

Gas Phase ◽

Density Functional ◽

Photophysical Properties ◽

Intramolecular Proton Transfer ◽

Time Dependent ◽

Functional Theory ◽

The Density Functional Theory ◽

The Impact ◽

Dependent Density

The impact of ion-π interactions on the photophysical properties of quinizarin have been investigated using the density functional theory and time-dependent density functional theory at the M06-2X/6-311++G(d,p) level in the gas phase and solution.

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An analogy study on ESIPT reaction for 3BHC sensor between polar DMF and nonpolar toluene

Canadian Journal of Chemistry ◽

10.1139/cjc-2017-0463 ◽

2017 ◽

Vol 95 (12) ◽

pp. 1303-1307

Author(s):

Dapeng Yang ◽

Min Jia ◽

Jingyuan Wu ◽

Xiaoyan Song ◽

Qiaoli Zhang

Keyword(s):

Excited State ◽

Density Functional ◽

Emission Spectra ◽

Dft Method ◽

Intramolecular Proton Transfer ◽

Nonpolar Solvent ◽

State Behavior ◽

Functional Theory ◽

Td Dft ◽

Intramolecular Hydrogen

A comparison about excited state intramolecular proton transfer (ESIPT) mechanism of a new sensor 3-(1,3-benzothiazol-2-yl)-2-hydroxynaphthalene-1-carbaldehyde (3BHC) in polar solvent dimethylformamide (DMF) and nonpolar solvent toluene have been investigated within the framework of the time-dependent density functional theory (TD-DFT) method. The reproduced previous experimental absorption and emission spectra via our calculations reveals the reasonability of the DFT and TD-DFT theoretical level. The staple bond lengths, bond angles, and corresponding infrared vibrational spectra demonstrate that the intramolecular hydrogen bond of 3BHC should be strengthened in both polar DMF and nonpolar toluene. Two kinds of ESIPT mechanisms for different solvents have been put forward; there is a low potential barrier in the ESIPT process in the DMF solvent, whereas there is almost a nonbarrier for the ESIPT process in the toluene solvent. Hence, we could conclude that the ESIPT process of 3BHC sensor is more likely to occur in the nonpolar solvent upon the photoexcitation, based on which, the excited state behavior of 3BHC could be controlled.

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Impact of Vibrations and Electronic Coherence on Electron Transfer in Flat Molecular Wires

MRS Advances ◽

10.1557/adv.2017.157 ◽

2017 ◽

Vol 2 (14) ◽

pp. 811-816 ◽

Cited By ~ 1

Author(s):

Oscar Grånäs ◽

Grigory Kolesov ◽

Efthimios Kaxiras

Keyword(s):

Electron Transfer ◽

Excited State ◽

Real Time ◽

Density Functional ◽

Molecular Wires ◽

The Real ◽

Velocity Autocorrelation ◽

Td Dft ◽

Electronic Coherence ◽

The Impact

ABSTRACTElectron transfer in molecular wires are of fundamental importance for a range of optoelectronic applications. The impact of electronic coherence and ionic vibrations on transmittance are of great importance to determine the mechanisms, and subsequently the type of wires that are most promising for applications. In this work, we use the real-time formulation of time-dependent density functional theory to study electron transfer through oligo-p-phenylenevinylene (OPV) and the recently synthesized carbon bridged counterpart (COPV). A system prototypical of organic photovoltaics is setup by bridging a porphyrin-fullerene dyad, allowing a photo-excited electron to flow between the Zn-porphyrin (ZnP) chromophore and the C60 electron acceptor through the molecular wire. The excited state is described using the fully self-consistent ∆-SCF method. The state is then propagated in time using the real-time TD-DFT scheme, while describing ionic vibrations with classical nuclei. The charge transferred between porphyrin and C60 is calculated and correlated with the velocity autocorrelation functions of the ions. This provides a microscopic insight to vibrational and tunneling contributions to electron transport in linked porphyrin-fullerene dyads. We elaborate on important details in describing the excited state and trajectory sampling.

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Hetarylazopyrazolone Dyes Based on Benzothiazole and Benzimidazole Ring Systems: Synthesis, Spectroscopic Investigation, and Computational Study

Journal of Chemistry ◽

10.1155/2017/8659346 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Ebru Aktan ◽

Tahsin Uyar

Keyword(s):

Density Functional Theory ◽

Density Functional ◽

Computational Study ◽

Benzimidazole Ring ◽

Acid Base ◽

Functional Theory ◽

Ring Systems ◽

Td Dft ◽

Elemental Analyses ◽

Experimental Values

In this study, the synthesized coupling component 1-(2-benzothiazolyl)-3-methylpyrazol-5-one reacted with diazotised heterocyclic amines to afford six novel hetarylazopyrazolone dyes. These azo dyes based on benzothiazole and benzimidazole ring systems were characterized by spectral methods and elemental analyses. The solvatochromic behaviors of these dyes in various solvents were evaluated. The ground state geometries of the dyes were optimized using density functional theory (DFT). Solvent, acid-base, and substituent influences on the wavelength of the maximum absorption were examined in detail. Time-dependent density functional theory (TD-DFT) calculations were performed to obtain the absorption spectra of the dyes in various solvents and the results compared with experimental values. Besides, frontier molecular orbitals (FMO) analysis for the dyes is also described from the computational process.

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Structural and Electronic Properties of Adenine-Thymine Basepair : A Computational Study

Dhaka University Journal of Science ◽

10.3329/dujs.v67i1.54572 ◽

2019 ◽

Vol 67 (1) ◽

pp. 51-54

Author(s):

Mohammad Alauddin ◽

Tapas Debnath ◽

Mohammed A Aziz

Keyword(s):

Hydrogen Bonding ◽

Electronic Properties ◽

Density Functional ◽

Computational Study ◽

Double Helix ◽

Molecular Systems ◽

Td Dft ◽

Life Phenomena ◽

Dna Double Helix ◽

Adenine Thymine

It is well known that stability of deoxyribo-nucleic acid (DNA) double helix depends on hydrogen bonding (HB) between adenine-thymine and guanine-cytosine. HB plays an important role in molecular systems, particularly in biological systems because all lives on the earth may be viewed as a matter of hydrogen-bonding supramolecular systems. Since HBs have a central role on the mechanism of life phenomena including the structure and functions, it is essential to understand the molecular-level aspects of HB systems. Therefore, we studied the structural properties of adenine-thymine (A-T) basepair theoretically using DFT/B3LYP/6-31G level of theory. Theoretically we found four isomers of A-T basepair and the most stable isomer is one in which adenine and thymine are connected via two hydrogen bonding. The electronic properties were calculated by Time Dependent Density Functional Theory (TD-DFT) approach. Dhaka Univ. J. Sci. 67(1): 51-54, 2019 (January)

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Studies on the Kinetics of Doxazosin Degradation in Simulated Environmental Conditions and Selected Advanced Oxidation Processes

Water ◽

10.3390/w11051001 ◽

2019 ◽

Vol 11 (5) ◽

pp. 1001 ◽

Cited By ~ 3

Author(s):

Joanna Karpinska ◽

Aneta Sokol ◽

Jolanta Koldys ◽

Artur Ratkiewicz

Keyword(s):

Environmental Conditions ◽

Density Functional ◽

Natural Waters ◽

Basic Medium ◽

Mechanistic Study ◽

Aqueous Environment ◽

Functional Theory ◽

Short Time ◽

The Impact ◽

Kinetics Of

The photochemical behavior of doxazosin (DOX) in simulated environmental conditions using natural waters taken from local rivers as a solvent was studied. The chemical characteristics of applied waters was done and a correlation analysis was used to explain the impact of individual parameters of matrix on the rate of the DOX degradation. It was stated that DOX is a photoliable compound in an aqueous environment. Its degradation is promoted by basic medium, presence of environmentally important ions such as Cl−, NO3−, SO42− and organic matter. The kinetics of DOX reactions with OH− and SO4− radicals were examined individually. The UV/H2O2, classical Fenton and photo-Fenton processes, were applied for the generation of hydroxyl radicals while the UV/VIS:Fe2(SO4)3:Na2SO2 system was employed for production of SO4− radicals. The obtained results pointed that photo-Fenton, as well as UV/VIS:Fe2(SO4)3:Na2SO2, are very reactive in ratio to DOX, leading to its complete degradation in a short time. A quantitative density functional theory (DFT) mechanistic study was carried out in order to explain the molecular mechanism of DOX degradation using the GAUSSIAN 09 program.

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Graft Purity and Composition Significantly Impact the Engraftment of Autologous Stem Cell Transplants

Blood ◽

10.1182/blood.v128.22.5733.5733 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5733-5733

Author(s):

Valentina Giai ◽

Stefania Tamiazzo ◽

Sabrina Leoncino ◽

Lia Mele ◽

Maria Matilde Ciriello ◽

...

Keyword(s):

Stem Cell ◽

Hodgkin Lymphoma ◽

Conditioning Regimen ◽

Consecutive Series ◽

Substantial Impact ◽

Cd34 Cells ◽

Wbc Count ◽

Clinical Records ◽

The Impact ◽

Kinetics Of

Abstract Background: Autologous stem cell transplantation (ASCT) has been widely used in the treatment of hematological malignancies over the last two decades. Despite its broad use, some characteristics that might influence engraftment have not been exhaustively investigated, particularly graft purity with respect to contamination by platelets (PLTS) and White Blood Cells (WBC). Here we report collection characteristics and engraftment kinetics of a single Center consecutive series of 510ASCTs. Methods: We retrospectively collected clinical records of patients who underwentleucapheresis procedures (LA; followed or not byASCT) at our Institution over 16 years (2000-2016): 290 patients collected peripheral blood stem cells (PBSC) (80 Multiple Myeloma MM, 133 Non Hodgkin Lymphoma NHL, 22 Hodgkin Lymphoma HL, 32 Acute Myeloid Leukemia AML, 23 other diseases) for a total of 481LAs. Mobilizing regimens are described in Table 1. We considered the number of harvested CD34+ cells *106/kg the first day of LA. Data on 458 patients (191 MM, 190 NHL, 45 HL, 19 AML and 13 other diseases) for a total of 510 ASCTs were acquired. The impact on engraftment kinetics of conditioning chemotherapies, amount of infused CD34+ cells and WBC/PLTS graft contamination were analyzed. Absolute neutrophil count (ANC) engraftment was defined as the duration of neutropenia (from day 0 to the first of 3 consecutive days of ANC>500/ul post ASCT). Results: Regarding CD34+ cell collection, no impact of mobilizing regimens and WBC count during LA was observed. On the other hand, we observed a difference in the number of total CD34+ cells collected among different diagnoses: the median overall collection was 7.2 (0.65-64.06)*106/kg CD34+ cells for NHL patients, 5.66 (0.71-23.31)*106/kg for MM patients, 6.15 (0.51-23.24) *106/kg for HL patients and 3.56 (0.64-20.3)*106/kg for AML patients) (p = 0.001). Considering CD34+ cells/kg harvested on the first day of LA, 59.2% of NHL and HL, 57.5% of MM patients and 34% of AML patients harvested ³ 5*106/Kg CD34+ cells. Of note, among AML patients, 40.6% collected less than 2.5*106/kg. The differences were statistically significant (p = 0.003) (Tab. 2). Moreover, an inverse correlation between collected CD34+ cells and age was shown (p = 0.001) (Fig.1). ANC recovery after ASCTwas not influenced by conditioning regimen whereas diagnosis impacted on the duration of neutropenia (AML patients displayed a longer aplasia, p < 0.01). We observed that the median days with ANC<500/ul were 10, 11 and 12 in patients who received >5.3*10^6/kg, 3.5-5.3*10^6/kg and <3.5*10^6/kg CD34+ cells, respectively (p <0.0001) (Fig 2a). Furthermore, the same finding was observed considering the duration of thrombocytopenia (median number of days with PLTS <50000/ul: 15, 18 and 20 in patients who received >5.3*10^6/kg, 3.5-5.3*10^6/kg and <3.5*10^6 CD34+ cells, p<0.0001) (Fig.2b). Looking at the apheresis product, we analyzed the impact of harvest contaminating WBC and PLTSon engraftment kinetics. Notably, when the ASCTcollection contained >100*103/ul WBC, ANC engraftment (days with ANC < 500/ul) lasted longer (median days 11) compared to patients who received a graft with lower WBC count (p < 0.0001) (Fig. 3a). A faster ANC engraftment was also observed in patients receiving harvests with PLTS levels >600*103/ul compared to those who infused a collection bag with PLTS <600*103/ul (p = 0.005) (Fig.3b,c). Conclusions: Herein, we confirmed that the disease and the amount of infusedCD34+ cells significantly influence time of ANC andPLTS engraftment; furthermore, we observed for the first time that quality and purity of the graft have a substantial impact on engraftment kinetics. Disclosures No relevant conflicts of interest to declare.

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Design of donor–acceptor copolymers for organic photovoltaic materials: a computational study

Physical Chemistry Chemical Physics ◽

10.1039/c7cp08176f ◽

2018 ◽

Vol 20 (5) ◽

pp. 3581-3591 ◽

Cited By ~ 20

Author(s):

Haydar Taylan Turan ◽

Oğuzhan Kucur ◽

Birce Kahraman ◽

Seyhan Salman ◽

Viktorya Aviyente

Keyword(s):

Density Functional ◽

Computational Study ◽

Time Dependent ◽

Organic Photovoltaic ◽

Functional Theory ◽

Organic Chromophores ◽

Photovoltaic Materials ◽

Td Dft ◽

Organic Photovoltaic Materials ◽

Donor Acceptor

80 different push–pull type organic chromophores which possess Donor–Acceptor (D–A) and Donor–Thiophene–Donor–Thiophene (D–T–A–T) structures have been systematically investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) at the B3LYP/6-311G* level.

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Computational Study of the Decomposition of Cyclotetramethylenetetranitramine under Impact, Friction, and Electric Fields

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.1096.407 ◽

2015 ◽

Vol 1096 ◽

pp. 407-412

Author(s):

Hui Hu ◽

Miao Miao Li ◽

Bao Shan Wang

Keyword(s):

Electric Fields ◽

Energetic Materials ◽

Density Functional ◽

Computational Study ◽

Minimum Energy ◽

High Energy ◽

High Energy Density ◽

Basis Sets ◽

Gas Phases ◽

The Impact

Organic CHNO-containing high energy density materials have been widely used for storing large amounts of the chemical energies which can be rapidly transformed into heat upon various external perturbations during detonation. The sensitivity of the energetic materials is subjected to considerable concern for safety and maintenance. Periodic density functional theory with the all-electron basis sets were employed in this work to unravel the impact, friction, and electric-fields induced decomposition of HMX. The minimum energy paths for the N−NO2homolysis reactions of HMX in the bulk and gas phases were obtained. The surface-enhanced effect on the decomposition of HMX were calculated for both (010) and (100) surfaces. A general theoretical scheme has been proposed to assess the intrinsic mechanic and electrostatic sensitivities of the pure energetic materials.

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Computer aided chemical design: using quantum chemical calculations to predict properties of a series of halochromic guaiazulene derivatives

Royal Society Open Science ◽

10.1098/rsos.160373 ◽

2016 ◽

Vol 3 (11) ◽

pp. 160373 ◽

Cited By ~ 5

Author(s):

Adam W. Woodward ◽

Ebrahim H. Ghazvini Zadeh ◽

Mykhailo V. Bondar ◽

Kevin D. Belfield

Keyword(s):

Data Storage ◽

Density Functional ◽

Computational Study ◽

Photophysical Properties ◽

Photon Absorption ◽

Optoelectronic System ◽

Dft Methods ◽

Two Photon Absorption ◽

Td Dft ◽

Calculation Results

With the scientific community becoming increasingly aware of the need for greener products and methodologies, the optimization of synthetic design is of greater importance. Building on experimental data collected from a synthesized guaiazulene derivative, a series of analogous structures were investigated with time-dependent density functional theory (TD-DFT) methods in an effort to identify a compound with desirable photophysical properties. This in silico analysis may eliminate the need to synthesize numerous materials that, when investigated, do not possess viable characteristics. The synthesis of several computationally investigated structures revealed discrepancies in the calculation results. Further refined computational study of the molecules yielded results closer to those observed experimentally and helps set the stage for computationally guided design of organic photonic materials. Three novel derivatives were synthesized from guaiazulene, a naturally occurring chromophore, exhibiting distinct halochromic behaviour, which may have potential in a switchable optoelectronic system or combined with a photoacid generator for data storage. The protonated forms were readily excitable via two-photon absorption.

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