Molecular Structure Optimization Research Articles

Enhanced CO2 electroreduction on Co active site of cobalt phthalocyanine by electronic effect

Metal phthalocyanines molecular catalysts exhibit the unique ability of CO2 electrochemical reduction reaction (CO2ERR) thanks to their well-defined macrocycle structure. In this work, we introduced different substituting functional groups at the phthalocyanine ring of cobalt phthalocyanine to study the relationship of molecular structure optimization and CO2ERR activity. An optimal nitro-substituted cobalt phthalocyanine catalyst can mediate CO2 to CO in a H-cell with maximum selectivity of ∼94% together with a current density of 12.6 mA cm−2 at −0.877 V vs. RHE. The insights of this work on designing and optimizing of the molecular catalysts contribute to lower energy as well as cost-effective CO2ERR.

Comparative study of DFT, AM1, and PM3 optimization methods modeling new psychotropic amphetamines

In order to improve the determination of physico-chemical descriptors of organic substances, it is necessary to optimize the computational representations of their molecular structures. The computerized estimation of these descriptors is especially useful in the case of drugs of abuse, as clinical studies are not recommended for new compounds belonging to classes known to have a high toxicity. The optimization of molecular structures allows the improvement of the accuracy in determining the physico-chemical descriptors and consequently of the associated quantitative structure - property or structure - activity relationships (QSAR). We are presenting a comparative study regarding the effect of the AM1, PM3, and DFT optimization methods, which were applied in the case of a series of new psychotropic amphetamines for their physico-chemical characterization based on molecular descriptors.

Synthesis of a Novel Filtrate Reducer and Its Application in Water-Based Drilling Fluid for Ultra-High-Temperature Reservoirs

The high-temperature stability and filtration property controlling of ultra-high-temperature water-based drilling fluids is a worldwide problem. To resolve this problem, a high-temperature-resistant quaternary copolymer (HTRTP) was synthesized based on molecular structure optimization design and monomer optimization. The physical and chemical properties were characterized by infrared spectroscopy, thermal weight, and spectrophotometry, and their temperature and salt resistance was evaluated in different drilling fluids, combined with adsorption, particle size analysis, and stability test. The results show that the thermal stability of HTRTP is very strong, and the initial temperature of thermal decomposition is above 320°C. The salt resistance of HTRTP is more than 162 g/L, and the calcium resistance is more than 5000 mg/L, which is equivalent to the foreign temperature-resistant polymer DCL-a, and is superior to the domestic metal ion viscosity increasing fluid loss agent PMHA-II for drilling fluids. It has excellent high-temperature resistance (245°C) and fluid loss reduction effect in fresh water base mud, fresh water weighted base mud, saturated brine base mud, and composite salt water base mud, which is better than foreign DCL-a (245°C) and domestic PMHA (220°C). The adsorption capacity of HTRTP on clay particles is large and firm, and the adsorption capacity changes little under the change of chemical environment and temperature. Both before and after HTRTP aging (245°C/16 h), the permeability of filter cake can be significantly reduced and its compressibility can be improved. By optimizing the particle size gradation of the drilling fluid and enhancing the colloid stability of the system, HTRTP can improve the filtration building capacity of the drilling fluid and reduce the filtration volume. The development of antithermal polymer provides a key treatment agent for the study of anti-high-temperature-resistant saline-based drilling fluid.

Effects of Heteroatom Substitution on the Photovoltaic Performance of Donor Materials in Organic Solar Cells

ConspectusOver the past few years, the innovation of narrow bandgap acceptor combined with wide bandgap donor materials significantly promotes the power conversion efficiencies (PCEs) of organic solar cells (OSCs) to exceed 18%. To build a state-of-the-art OSC, absorption spectra, frontier molecular orbital energy levels, molecular packing and crystallinity, and charge carrier mobilities of the photovoltaic materials should be considered in their molecular design. The donor and acceptor materials are the key components determining the photovoltaic performance of the OSCs. The side chain engineering on the conjugated backbone is a critical strategy to optimize the photovoltaic properties of the donor materials. In this Account, we focus on the topic of heteroatom substitution on the molecular backbone of the donor materials for improving their photovoltaic performance, aiming to provide in-depth understanding of the molecular structure optimization for the design of state-of-the-art photovoltaic materials.First, we highlight the halogen (fluorine and chlorine) atom substitution strategies applied on the conjugated molecular backbone of the organic photovoltaic materials. The strong electronegativity of halogen atoms can downshift the highest occupied molecular orbital (HOMO) energy levels of the donor materials, which could increase open-circuit voltages of the resulting OSCs. In addition, the hydrogen bonding aroused by the halogen atoms is beneficial to improve their charge transport property and crystallinity of the organic semiconductors. On the other hand, flexible side chains are critical components for improving the solubility of the photovoltaic materials. Using the flexible side chains of alkylthio and alkylsilyl is an easy and effective approach to tune the electronic energy levels and absorption spectra of the photovoltaic materials. Due to the formation of pπ(C)–dπ(S) orbital overlap, the empty 3d-orbitals of the sulfur atom in the alkylthio substituents can accept the π-electron of conjugated skeleton to modulate the optical and electrical properties of the photovoltaic materials. Similarly, the silicon atom in the alkylsilyl side chains can stabilize the lowest unoccupied molecular orbital (LUMO) level and downshift the HOMO level of the organic semiconductor, which leads to the improved photovoltaic performance of the organic donor materials. Finally, we briefly discussed the challenges for the photovoltaic materials toward performance optimization and practical application of the OSCs.

Computational, spectroscopic, Hirshfeld surface, electronic state and molecular docking studies on phthalic anhydride

Phthalic anhydride (PA) was studied Spectroscopically by NMR (1H NMR and 13C NMR), FT-IR, UV-Visible and quantum chemically by DFT approach.3D and 2D surface analysis was carried by Hirshfeld surface. B3LYP method and 6-311++G(d,p) basis set were employed for optimization of molecular structure and for calculation of wave numbers of normal modes of vibrations. Detailed description of intermolecular interactions of crystal surface was done by 3D Hirshfeld surface analysis and 2D finger print plots. Hirshfeld surface also helps to explore intermolecular interactions in PA crystal. Hole and Electron density distribution maps were drawn in 2 different excited states of higher oscillatory strength with DMSO, MeOH as solvents. Structure was optimized and optimized bond lengths and angles were compared with the experimental bond lengths and Bond angle Parameters, were found in good agreement with each other. Complete potential energy distribution assignments were done successfully by VEDA. 1H NMR and 13C NMR shifts were estimated by GIAO method and results were compared with experimental spectra. TDDFT method and PCM solvent model was utilized for electronic property analysis such as UV–Vis (in gas phase, ethanol and DMSO) and compared with the experimental UV–Vis spectra. The HOMO/LUMO energy results emphasize adequate charge transfer is happened within the molecule. Study of donor-acceptor interconnections were done via NBO analysis. MEP surface analysis was done to demonstrate charge distribution in molecule. The degree of relative localization of electrons was analyzed via FLF Diagram. The Fukui function analysis give information regarding possible sites for attacks by different substituents. Molecular electrostatic potential (MEP) surface was drawn for analysis of reactive sites via 3-D colour representation. The biological study such as molecular docking was done with 6 different receptors to find the best ligand protein interactions and drug likeness was also carried out and found drug like character.

Detailed structural investigation of Crizotinib and the exploration of its antitumor potential by DFT calculations and molecular docking

Detailed structural investigation and exploration of the potential clinical indications are necessary for the drug reevaluation of newly-approved drugs. Crizotinib is a potent and selective receptor tyrosine kinases (RTK) dual inhibitor approved for treatment of non-small cell lung carcinoma (NSCLC) by FDA. In this work, a detailed structural research of Crizotinib molecule including molecular structural optimization, Mulliken population, molecular electrostatic potential, vibrational frequencies have been performed by theoretical calculations. The chiral structure was also examined by experimental and simulated electrostatic circular dichroism (ECD) spectrum at different calculation levels. Moreover, the potential clinical indications of Crizotinib are also predicted by molecular docking based on increasing case reports in curation of various cancers. The molecular docking data supported the potential interaction of Crizotinib with various therapeutic targets. In addition to the acknowledged interactions with therapeutic target for NSCLC (C-met, ALK, NTRK), some other targets such as PD-1 and POM121 for breast and prostatic cancer, respectively, were firstly observed to be able to interact with Crizotinib, which have been confirmed by the recent clinical findings. Our research provided a probable explanation of the unique therapeutic effect of Crizotinib for breast and prostatic cancer, and also guided a way for new clinical uses for old drug such as Crizotinib.

Chemical Design for Both Molecular and Morphology Optimization toward High‐Performance Lithium‐Ion Batteries Cathode Material Based on Covalent Organic Framework

AbstractIn most cases, to obtain high‐performance electrode materials for lithium‐ion batteries (LIBs), it is necessary to optimize both their molecular structure and morphology. Normally, the molecular structure of covalent organic frameworks (COFs) can be well engineered by chemical design, while their morphology is mainly optimized by post‐processing. Herein, by introducing a flexible building unit containing sp3 N redox‐active centers, a bipolar‐type TP‐TA COF assembled by uniform 2D hexagonal nanosheets is synthesized in a one‐step reaction without any post‐processing, achieving the highly challenging simultaneous optimization of both molecular structure and morphology required for high‐performance electrode materials. Thus, when used as cathode material for LIBs, its combined optimized chemical structure and favorable morphology of TP‐TA COF synergistically render a high capacity (207 mA h g−1 at 200 mA g−1), excellent rate performance (129 mA h g−1 at 5.0 A g−1), and cycling stability (93% capacity retention after 1500 cycles at 5.0 A g−1).

Potential Landscape of a Probe Penetrant Particle for Fast Estimating of Silica Diffusion Properties

Successful search for optimal molecular structures of membrane materials requires efficient algorithms for assessing their diffusion properties. It is shown in this work that the potential landscape of a probe penetrating particle, a component that passes through the membrane during gas separation, is suitable for solving such problems. A number of indicators are considered that can be easily calculated from potential landscapes of specific models of silicate materials, both not related to the topology of the potential landscape (global minimum, voxel energy distribution), and depending on it (percolation cluster). A good correlation of these indicators with the corresponding diffusion coefficients is shown

Data-Driven Ionic Liquid Design for CO2 Capture: Molecular Structure Optimization and DFT Verification

Data-Driven Ionic Liquid Design for CO₂ Capture: Molecular Structure Optimization and DFT Verification

Control of aggregated structure of photovoltaic polymers for high‐efficiency solar cells

Abstractπ‐Conjugated organic/polymer materials‐based solar cells have attracted tremendous research interest in the fields of chemistry, physics, materials science, and energy science. To date, the best‐performance polymer solar cells (PSCs) have achieved power conversion efficiencies exceeding 18%, mostly driven by the molecular design and device structure optimization of the photovoltaic materials. This review article provides a comprehensive overview of the key advances and current status in aggregated structure research of PSCs. Here, we start by providing a brief tutorial on the aggregated structure of photovoltaic polymers. The characteristic parameters at different length scales and the associated characterization techniques are overviewed. Subsequently, a variety of effective strategies to control the aggregated structure of photovoltaic polymers are discussed for polymer:fullerene solar cells and polymer:nonfullerene small molecule solar cells. Particularly, the control strategies for achieving record efficiencies in each type of PSCs are highlighted. More importantly, the in‐depth structure–performance relationships are demonstrated with selected examples. Finally, future challenges and research prospects on understanding and optimizing the aggregated structure of photovoltaic polymers and their blends are provided.

Chemical computational approaches for optimization of effective surfactants in enhanced oil recovery

Abstract The surfactant flooding becomes an attractive method among several Enhanced Oil Recovery (EOR) processes to improve the recovery of residual oil left behind in the reservoir after secondary oil recovery process. The designing of a new effective surfactant is a comparatively complex and often time consuming process as well as cost-effective due to its dependency on the crude oil and reservoir properties. An alternative chemical computational approach is focused in this article to optimize the performance of effective surfactant system for EOR. The molecular dynamics (MD), dissipative particle dynamics (DPD) and density functional theory (DFT) simulations are mostly used chemical computational approaches to study the behaviour in multiple phase systems like surfactant/oil/brine. This article highlighted a review on the impact of surfactant head group structure on oil/water interfacial property like interfacial tensions, interface formation energy, interfacial thickness by MD simulation. The effect of entropy in micelle formation has also discussed through MD simulation. The polarity, dipole moment, charge distribution and molecular structure optimization have been illustrated by DFT. A relatively new coarse-grained method, DPD is also emphasized the phase behaviour of surfactant/oil/brine as well as polymer-surfactant complex system.

Synthesis, crystal structure and electronic applications of monocarboxylic acid substituted phthalonitrile derivatives combined with DFT studies

Monocarboxylic acid substituted phthalonitrile derivatives (PN1 and PN2) have been synthesized and their molecular geometries and hydrogen bond interactions investigated with single cystal X-ray diffraction analysis. PN1-a and PN2 crystal structures linked by a pair of O–H⋯O hydrogen bonds form classical carboxylic acid inversion dimers, whilst PN1-b crystal structure stabilized by classical O–H⋯O and O–H⋯N hydrogen bonding interactions. Spectral characterizations of PN1-a and PN2 structures have been performed by FT-IR, 1H-13C NMR and UV-Vis techniques. Molecular structure optimization and structural properties of PN1 and PN2 in the forms of monomer and dimer have been studied with the DFT approach, B3LYP functional and 6-311++G(d,p) basis set. The effects of dimeric forms of structures on geometrical and spectral parameters have been evaluated together with the values of monomeric forms and experimental ones. Concepts specific to electronic absorption spectra such as absorption wavelengths and major contributions to electronic transitions and FMOs energy values have been determined by TD-DFT approach. Some reactivity properties of the monomer PN1-a and PN2 structures have been evaluated through global, local parameter values and MEP visuals. It was shown that PN2 monomer structure which has both a low HOMO-LUMO energy gap (ΔE=3.83 eV) and a higher chemical softness value (S=0.52 eV−1) is more reactive than PN1-a monomer. The potentials of being nonlinear optical (NLO) material and some thermodynamic parameters that are thought to contribute to their structural properties have been determined theoretically for PN1-a and PN2 monomeric forms. Furthermore, it is determined that PN2 has superior properties compared to PN1 based on the electrical characterization of the compounds.

Physical properties and biological activity of methyldopa drug carrier cellulose derivatives. Theoretical study

The complete computational study of the methyldopa drug and its derivatives prodrug 1-4(methyldopa-cellulose (Ce), methyldopa-carboxymethyl cellulose(CMC), methyldopa-maleic anhydride cellulose (MAC)and methyldopa-hydroxypropyl cellulose(HPC)) was performed by Density Function theory method with the Becker’s three parameter hybrid functional (B3LYP) functional and 6-31G++ (d, p) basis set using Gaussian 09 program. The Density Function theory (DFT) DFT method is used to calculate the optimal molecular structure, vibrational spectra, highest occupied molecular orbital energies (HOMO), lowest unoccupied molecular orbital energies (LUMO), electronic properties (total energy, dipole moment, electronegativity, chemical hardness and softness), biological activity, and molecular surfaces. Using the reaction coordinate method to quantify the energy enthalpy and activation energy of O-R bond rupture. The result shows the derivatives that are hoped to have preference in their use as carriers are (methyldopa-Ce) and (methyldopa-MAC), which gave the drug acid as a product of the O-R bond breaking process in an irreversible reaction.

Discovery of a Pyrimidinedione Derivative as a Potent and Orally Bioavailable Axl Inhibitor.

The receptor tyrosine kinase Axl plays important roles in promoting cancer progression, metastasis, and drug resistance and has been identified as a promising target for anticancer therapeutics. We used molecular modeling-assisted structural optimization starting with the low micromolar potency compound 9 to discover compound 13c, a highly potent and orally bioavailable Axl inhibitor. Selectivity profiling showed that 13c could inhibit the well-known oncogenic kinase Met with equal potency to its inhibition of Axl superfamily kinases. Compound 13c significantly inhibited cellular Axl and Met signaling, suppressed Axl- and Met-driven cell proliferation, and restrained Gas6/Axl-mediated cancer cell migration or invasion. Furthermore, 13c exhibited significant antitumor efficacy in Axl-driven and Met-driven tumor xenograft models, causing tumor stasis or regression at well-tolerated doses. All these favorable data make 13c a promising therapeutic candidate for cancer treatment.

Optimizing Molecular Geometries in Strong Magnetic Fields.

An efficient implementation of geometrical derivatives at the Hartree–Fock (HF) and current-density functional theory (CDFT) levels is presented for the study of molecular structure in strong magnetic fields. The required integral derivatives are constructed using a hybrid McMurchie–Davidson and Rys quadrature approach, which combines the amenability of the former to the evaluation of derivative integrals with the efficiency of the latter for basis sets with high angular momentum. In addition to its application to evaluating derivatives of four-center integrals, this approach is also applied to gradients using the resolution-of-the-identity approximation, enabling efficient optimization of molecular structure for many-electron systems under a strong magnetic field. The CDFT contributions have been implemented for a wide range of density functionals up to and including the meta-GGA level with current-density dependent contributions and (range-separated) hybrids for the first time. Illustrative applications are presented to the OH and benzene molecules, revealing the rich and complex chemistry induced by the presence of an external magnetic field. Challenges for geometry optimization in strong fields are highlighted, along with the requirement for careful analysis of the resulting electronic structure at each stationary point. The importance of correlation effects is examined by comparison of results at the HF and CDFT levels. The present implementation of molecular gradients at the CDFT level provides a cost-effective approach to the study of molecular structure under strong magnetic fields, opening up many new possibilities for the study of chemistry in this regime.

The Complex Structure of Protein AaLpxC from Aquifex aeolicus with ACHN-975 Molecule Suggests an Inhibitory Mechanism at Atomic-Level against Gram-Negative Bacteria.

New drugs with novel antibacterial targets for Gram-negative bacterial pathogens are desperately needed. The protein LpxC is a vital enzyme for the biosynthesis of lipid A, an outer membrane component of Gram-negative bacterial pathogens. The ACHN-975 molecule has high enzymatic inhibitory capacity against the infectious diseases, which are caused by multidrug-resistant bacteria, but clinical research was halted because of its inflammatory response in previous studies. In this work, the structure of the recombinant UDP-3-O-(R-3-hydroxymyristol)-N-acetylglucosamine deacetylase from Aquifex aeolicus in complex with ACHN-975 was determined to a resolution at 1.21 Å. According to the solved complex structure, ACHN-975 was docked into the AaLpxC’s active site, which occupied the site of AaLpxC substrate. Hydroxamate group of ACHN-975 forms five-valenced coordination with resides His74, His226, Asp230, and the long chain part of ACHN-975 containing the rigid alkynyl groups docked in further to interact with the hydrophobic area of AaLpxC. We employed isothermal titration calorimetry for the measurement of affinity between AaLpxC mutants and ACHN-975, and the results manifest the key residues (His74, Thr179, Tyr212, His226, Asp230 and His253) for interaction. The determined AaLpxC crystal structure in complex with ACHN-975 is expected to serve as a guidance and basis for the design and optimization of molecular structures of ACHN-975 analogues to develop novel drug candidates against Gram-negative bacteria.

Preclinical evaluation of [68Ga]Ga-MALAT-1-antisense oligonucleotides for specific PET imaging of MALAT-1 expressing tumours.

The present study was to explore the feasibility of developing positron molecular probes for the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1), to evaluate the distribution and pharmacokinetics, and to explore whether the probe can be used for the imaging of malignant tumours with high MALAT-1 expression in vivo. [68Ga]Ga labelling of MALAT-1 antisense oligonucleotides ([68Ga]Ga-MALAT-1-ASO) was synthesized by the conjugation of MALAT-1-NOTA-ASO and [68Ga] Ga3+. The radiochemical purity was shown by radio-HPLC. Pharmacokinetic studies and cellular uptake studies were performed. The biodistribution and metabolism of [68Ga] Ga-MALAT-1-ASO in normal ICR and MHCC-LM3 xenograft-bearing nude mice were studied in vitro and in vivo. [68Ga]Ga-MALAT-1-ASO was obtained in 98% radiochemical yield from a 10-min synthesis with 100 ± 50 MBq/nmol specific activity and >99% radiochemical purity. The Log D was -2.53 ± 0.19. The tracer displayed excellent stability in vitro. 68Ga-MALAT-1 ASO showed satisfactory binding ability to MHCC-LM3 cells; the biodistribution of [68Ga]Ga-MALAT-1-ASO in MHCC-LM3 tumour-bearing mice demonstrated specific uptake of the radiotracer (3.04 ± 0.11%ID/g). Micro-PET images of the MHCC-LM3 cell xenograft mouse model provided further evidence to support the hypothesis that [68Ga]Ga-MALAT-1-ASO can target tumours in vivo. We conclude that [68Ga]Ga labelling of MALAT-1 ASO is a convenient approach. The high accumulation of [68Ga]Ga-MALAT-1-ASO for tumours expressing MALAT-1 suggests that this radio compound may be used as a potential positron molecular probe. Molecular structure optimization studies need to be more in-depth to further reduce its background uptake and enhance tumour targeting.

Sustainable dyeing of cotton fabric with reactive dye in silicone oil emulsion for improving dye uptake and reducing wastewater

From sustainable chemistry and engineering perspectives, water and energy consumption are arguably the main issues in the textile industry. Thus, a silicone reverse emulsion dyeing system is developed to dye cellulosic textile with reactive dye. When the amount of dye is the same, the color depth of dyed cotton fiber is 13.82 and the fixation of dye is 87.76% in the silicone reverse emulsion dyeing system. In traditional water-based dyeing system, the color depth of dyed cotton fiber and the fixation of dye is only 9.31, 56.63% respectively. The silicone reverse emulsion dyeing technology does not consumes salts, but it can improve the dye fixation by 31.13%, and decreases the dye discharge by 72.41%. For the hydrolysis of bifunctional reactive dye, the main hydrolysis reaction is the individual hydrolysis of monochlorotriazine or vinyl sulfone at the prophase of hydrolysis. After 30 min, the additional β-hydroxyethyl sulfone and hydroxyl triazine dye are hydrolyzed to dihydroxyl dye. To confirm the hydrolytic reaction energy of dye in different dyeing system, the optimization of molecular structure, the hydrolysis reaction gap and the distribution of electron density on the dye were investigated using density functional theory. The hydrolytic reaction energy gap of bifunctional reactive dye is higher in silicone reverse emulsion dyeing system than that in traditional aqueous dyeing system, resulting the hydrolysis of dye is difficult in silicone oil emulsion dyeing system. The electron density is distributed almost entirely on the carbon–carbon double bond and triazine group in the HOMO of the dye, resulting in the LUMO of dyes can attacked by HOMO of hydroxyl anion. These successful investigations of the dyeing performance and the hydrolysis mechanism of dye explain that reactive dye can keep a long reactivity to fiber and effectively reduce the number of washing times, which greatly reduces the discharge of dyeing waste water.

MLIMC: Machine Learning-Based Implicit-Solvent Monte Carlo.

Monte Carlo (MC) methods are important computational tools for molecular structure optimizations and predictions. When solvent effects are explicitly considered, MC methods become very expensive due to the large degree of freedom associated with the water molecules and mobile ions. Alternatively implicit-solvent MC can largely reduce the computational cost by applying a mean field approximation to solvent effects and meanwhile maintains the atomic detail of the target molecule. The two most popular implicit-solvent models are the Poisson-Boltzmann (PB) model and the Generalized Born (GB) model in a way such that the GB model is an approximation to the PB model but is much faster in simulation time. In this work, we develop a machine learning-based implicit-solvent Monte Carlo (MLIMC) method by combining the advantages of both implicit solvent models in accuracy and efficiency. Specifically, the MLIMC method uses a fast and accurate PB-based machine learning (PBML) scheme to compute the electrostatic solvation free energy at each step. We validate our MLIMC method by using a benzene-water system and a protein-water system. We show that the proposed MLIMC method has great advantages in speed and accuracy for molecular structure optimization and prediction.

Recent Advances in The Polymer Dispersed Liquid Crystal Composite and Its Applications.

Polymer dispersed liquid crystals (PDLCs) have kindled a spark of interest because of their unique characteristic of electrically controlled switching. However, some issues including high operating voltage, low contrast ratio and poor mechanical properties are hindering their practical applications. To overcome these drawbacks, some measures were taken such as molecular structure optimization of the monomers and liquid crystals, modification of PDLC and doping of nanoparticles and dyes. This review aims at detailing the recent advances in the process, preparations and applications of PDLCs over the past six years.