AM1 Calculations Research Articles

Chiral Recognition of Butylone by Methylated β-Cyclodextrin Inclusion Complexes: Molecular Calculations and Two-Level Factorial Designs.

The integration of molecular docking and AM1 calculations has elucidated the complexation behavior of butylone enantiomers with methylated β-cyclodextrin derivatives. Our study reveals that butylone can adopt two distinct conformations within the β-cyclodextrin cavity, with one conformation being preferentially stabilized due to its favorable binding energy. This conformation preference is influenced by the methylation at the O2, O3, and O6 positions of β-cyclodextrin, which significantly affects complex stability and solvation properties. Factorial design analysis further highlights the critical role of these methylation sites in modulating the complexation energies. The heptakis(2,6-di-O-methyl)-β-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin exhibit distinct enantioseparation mechanisms for butylone, attributed to variations in hydrogen bonding and cavity interactions. This theoretical investigation not only corroborates experimental findings but also offers a detailed understanding of the molecular mechanisms underlying chiral recognition of butylone by methylated β-cyclodextrins. These insights facilitate the rational design of novel chiral selectors for analytical and separation applications. Future research can build upon these findings to explore similar interactions with other chiral synthetic cathinones, potentially advancing predictive capabilities and reducing experimental costs in chiral separation technology development.

Alkane/Water Partition Coefficient Calculation Based on the Modified AM1 Method and Internal Hydrogen Bonding Sampling Using COSMO-RS.

We introduce a physics-based model for calculating partition coefficients of solutes between water and alkanes, using a combination of a semi-empirical method for COSMO charge density calculation and statistical sampling of internal hydrogen bonds (IHBs). We validate the model on the experimental partition data (∼3500 molecules) of small organics, drug-like molecules, and statistical assessment of modeling of proteins and ligand drugs. The model combines two novel algorithms: a bond-correction method for improving the calculation of COSMO charge density from AM1 calculations and a sampling method to deal with IHBs. From a comparison of simulated and experimental partition coefficients, we find a root-mean-square deviation of roughly one log 10 unit. From IHB analysis, we know that IHBs can be present in two states: open (in water) and closed (in apolar solvent). The difference can lead to a shift of as much as two log 10 units per IHB; not taking this effect into account can lead to substantial errors. The method takes a few minutes of calculation time on a single core, per molecule. Although this is still much slower than quantitative structure–activity relationship, it is much faster than molecular simulations and can be readily incorporated into any screening method.

Synthesis, Hirshfeld surface analysis, DFT calculations, photoluminescence, spectroscopic and second order non linear optical studies on ammonium hydrogensquarate squaric acid monohydrate crystal

A new nonlinear optical material, Ammonium hydrogensquarate squaric acid monohydrate (AHSAM) has been synthesized. Single crystals of AHSAM have been grown successfully by slow evaporation solution technique (SEST). The grown AHSAM crystals have been subjected to Single crystal X-ray diffraction analysis (XRD), Hirshfeld surface analysis, Fourier transform infrared spectroscopy (FT-IR), Fourier transform Raman (FT-R) spectroscopy, Calculated and experimental ultraviolet–visible spectral analysis, Photoluminescence, Microhardness and second harmonic generation (SHG). From X-ray diffraction studies it shows that the structure belongs to monoclinic structure with space group C2/c. Hirshfeld surface analysis used to clarify the intra and intermolecular interactions in a visual manner. The molecular geometries are compared with AM1, HF and Density Functional Theory calculations and it shows good agreement with experimental data. The Frontier molecular orbital energy gap is found by TD-DFT method with HOMO-LUMO calculation. The second order NLO studies for AHSAM crystal is done by Kurtz and Perry powder technique.

REKAYASA STRUKTUR AKSEPTOR PADA ZAT WARNA ORGANIK TIPE D- π -A DENGAN KERANGKA TIOFEN

This research study about tiofen based organic dyes with D-π-A type as sensitizer on DSSC. The dyes were varied with the acceptor chain and were given names of dyes 1 to 10. The dye with the smallest band gap was added with the electron withdrawing and donating groups. The computational study used the hyperchem package with the AM1 calculation method. The result showed that dye 8 has the smallest band gap is 4,9 eV and dipole moment is 9,3 D. The effect of adding Cl as an electron withrawing group (EWG) can reduce the band gap value to 4,7 eV. The conclusions are that dye 8 is more potential as sensitizer on DSSC and the addition of Cl as EWG can improve the light harvesting efficiency.

Cover Feature: After Salisbury Nerve Agents Revisited (Mol. Inf. 8‐9/2019)

The Cover Picture shows the Novichok agent A 242 as reported by V. Mirayanov. The agents were developed in Russia by scientists at the GOSSNIIOkhT institute in Moscow (V. S. Mirzayanov, State Secrets. An insider's chronicle of the Russian chemical weapons program, Outskirts, Press, 2009, 604 pages. The photo was generated based on AM1 calculations (OASIS software). More Details can be found in the Full Paper by Lars Carlsen, please see DOI: 10.1002/minf.201800106. 8-9/2019 .

α‐Hydroxy‐Tetrazoles as Latent Ethynyl Moieties: A Mechanistic Investigation

This article focuses on the dehydration of α‐hydroxy‐tetrazoles, leading to tetraazafulvenes and then to vinylic carbenes that rearrange into ethynyl moieties through the Fritsch–Buttenberg–Wiechell rearrangement. Each step of this sequence was scrutinized, either by examination of the substrate and/or dehydrating agent scope, or through AM1 calculations, in order to understand the limiting step of this process. This underrated transformation appears to be a viable alternative to existing methods used for transforming aldehydes into alkynes.

Synthesis and Structure of a Longitudinally Twisted Hexacene.

The addition of phenyllithium to a polycyclic quinone, 9,11,12,21,22,24-hexaphenyltetrabenzo[a,c,n,p]hexacene-10,23-dione (10), followed by SnCl2 -mediated reduction of the diol intermediate, yielded 9,10,11,12,21,22,23,24-octaphenyltetrabenzo-[a,c,n,p]hexacene (4). Crystallographic analysis of hexacene 4 showed it to possess a longitudinal twist of 184°, which was in good agreement with AM1 calculations. In addition to being the most twisted acene synthesized to this point, compound 4 contains within its substructure the most twisted naphthalene, anthracene, tetracene, and pentacene moieties described.

Quantitative Analysis of Relationship Structure and Anionic Surfactant Micelle Concentration Critic With Semiempiris AM1

This research determines the mathematical equation which calculate the Concentration Micelle Critic theoretical anionic surfactant. The research was conducted the depiction of each surfactant anionic three-dimensional compound models, followed by optimizing the model structure anionic surfactant by using AM1 calculation method. Furthermore the calculation of descriptors (QSPR method), then it was analyzed statistically using Multiple Linear Regression (MLR). The results of statistical calculations showed that to calculate the theoretical CMC anionic surfactant can use the QSPR equation: log CMC = 4.157+0.118qC1+7.698qC2+0.425α–0.010µ-0.129RD–0.138 log P+0.021BM–0.034Avdw, n = 100 ; r = 0.927 ; r2 = 0.860 ; SE = 0.352 ; F= 30.888 ; PRESS = 23.506

ChemInform Abstract: N‐Arylazetidines: Preparation Through Anionic Ring Closure.

We report herein an efficient synthesis of diversely substituted N-aryl-2-cyanoazetidines based on an anionic ring-closure reaction. These compounds can be prepared from β-amino alcohols in enantiomerically pure form through a three-step sequence involving (i) copper-catalyzed N-arylation, (ii) N-cyanomethylation of the secondary aniline, and (iii) one-pot mesylation followed by ring closure induced by a base. This high-yielding sequence gives access to azetidines with a predictable and adjustable substitution pattern and also with predictable diastereoselectivity. These compounds are susceptible to multiple further derivatizations through Suzuki coupling or nitrile transformation, thus appearing as valuable new scaffolds for medicinal chemistry. Their rigid shape, featuring an almost planar N-arylamine and a planar four-membered ring, was revealed by both AM1 calculations and X-ray crystallography.

Three novel bolaamphiphiles as corrosion inhibitors for carbon steel in hydrochloric acid: Experimental and computational studies

Three novel bolaamphiphiles were synthesized and investigated as corrosion inhibitors for carbon steel in 1M HCl using chemical and electrochemical techniques. The results revealed that the synthesized bolaamphiphiles have good inhibitive effect. The adsorption of bolaamphiphiles on the carbon steel surface in 1M HCl was found to obey Langmuir isotherm. Polarization results showed that these inhibitors act as mixed-type inhibitors. The inhibition efficiency of the investigated bolaamphiphiles against the corrosion of carbon steel surface was studied by means of semi empirical molecular orbital AM1 calculations. The calculations showed a good correlation between the calculated quantum chemical parameters and the experimental data.

N-Arylazetidines: Preparation through Anionic Ring Closure

We report herein an efficient synthesis of diversely substituted N-aryl-2-cyanoazetidines based on an anionic ring-closure reaction. These compounds can be prepared from β-amino alcohols in enantiomerically pure form through a three-step sequence involving (i) copper-catalyzed N-arylation, (ii) N-cyanomethylation of the secondary aniline, and (iii) one-pot mesylation followed by ring closure induced by a base. This high-yielding sequence gives access to azetidines with a predictable and adjustable substitution pattern and also with predictable diastereoselectivity. These compounds are susceptible to multiple further derivatizations through Suzuki coupling or nitrile transformation, thus appearing as valuable new scaffolds for medicinal chemistry. Their rigid shape, featuring an almost planar N-arylamine and a planar four-membered ring, was revealed by both AM1 calculations and X-ray crystallography.

Nanopharmaceutical approach of epiisopiloturine alkaloid carried in liposome system: preparation and in vitro schistosomicidal activity.

Schistosomiasis is a neglected tropical disease caused by blood flukes of the genus Schistosoma. This disease control has been widely made by praziquantel-reference drug, but resistance to this drug has already been found. There has been the finding of an imidazole alkaloid in jaborandi leaves-epiisopiloturine, which has known activity against adult, young and egg forms of Schistosoma mansoni. This alkaloid is an apolar molecule with difficult solubility; therefore, the liposomal structure of epiisopiloturine was proposed. Liposomes are carrying structures of drugs that may enhance solubility of compounds such as epiisopiloturine. In this work, we report in vitro epiisopiloturine-loaded liposomes effect formed by different concentrations of lipids 9:1 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol and 8:2 (weight ratio) dipalmitoylphosphatidylcholine:cholesterol. Results have showed that epiisopiloturine extraction and isolation have been successful through high-performance liquid chromatography-HPLC and its purity confirmed through mass spectrometry has showed 287 Da molecular mass. Formulations from 9:1 DPPC:cholesterol and 8:2 DPPC:cholesterol with loaded EPI (300 microg/ml) have killed parasites at 100% after incubation 96 h and 120 h, respectively. Confocal microscopy employed to observe morphological alterations in the tegument of adult form of Schistosoma mansoni. Details from interaction, between epiisopiloturine and liposome, have been achieved by semi-empirical AM1 calculations, which have showed that epiisopiloturine inside is more stable than the outside form, at least 10 kcal. This is first time that schistosomicidal activity has been reported for epiisopiloturine-loaded into liposome.

Interaction studies of Alzheimer's Cathepsin B protein with inhibitors in presence and absence of water

Background The accuracy of ligand-protein docking may be affected by the presence of water molecules on the surface of proteins. Water can form complex bridging networks and can play a critical role in dictating the binding mode of ligands. A recent analysis of high-resolution crystal structures of ligand-protein complexes revealed that 85% of the complexes had one or more water molecules bridging the interaction between ligand and protein. For predicting the binding modes and energies of protein-ligand interactions, molecular docking methods are commonly used. In order to obtain an accurate complex geometry and binding energy estimation, an appropriate method for calculating partial charges is essential. AutoDockTools software, widely used as interface for preparing input files, utilizes the either Gasteiger or Kollman partial charge calculation method for both protein and ligand charge calculations. However, it has already been reported that more accurate partial charge calculation and as a consequence, more accurate docking can be achieved by using quantum chemical methods. In common practice so far, the quantum chemical partial charges were applied to the ligands for docking calculations. The newly developed Mozyme function of MOPAC2009 allows fast partial charge calculation of proteins by quantum mechanical semiempirical methods. Thus, in the current study, we use the semi-empirical quantum-mechanical partial charge calculations to investigate the interaction energies and polarization effects of the various components of the binding pocket on a set of Cathepsin B protein. Results The docking accuracy was computed by using the original AutoDock scoring function with the set of 19 protein ligand complexes using Gasteiger, AM1 and PM3 partial charge calculation methods. This helped us to compare the effect of the partial charge calculation method on docking accuracy. It was seen that the docking accuracy in regard to complex geometry significantly increased when partial charges of the ligands and proteins were calculated with the semi-empirical PM3 method. Our results demonstrate that (i) the energetic of the key water molecule are more favorable for the binding site in the Cathepsin B protein (ii) Water bridging and triangle formation were seen between the key amino acid residue and the ligand (iii) The internal energy is significant factor for the binding modes of various ligands. It was also observed a statistically significant overall increase in accuracy when water molecules are included during docking simulations. Out of the 19 complexes analyzed in the course of our study, the geometry of 17 complexes were accurately calculated using PM3 partial charges, while the use of Gasteiger charges resulted in only 8 accurate geometries. Conclusion Our findings indicate that the inclusion of water molecules in ligand-protein docking results in significant increases in docking accuracy when the use of quantum chemical partial charge assignment on both ligand and proteins for predicting the docking simulations.

CARCINOGENICITY OF CARBENDAZIM AND ITS METABOLITES

The carcinogenic potential of carbendazim and its metabolites was analyzed using statistical treatment of electronic parameters obtained from DFT/ 6-311++G(d,p) and AM1 calculations. The carcinogen-DNA interaction is described in the framework of the theory of unsynchronized resonance of covalent bond as a process of electron transfer involving the HOMO and LUMO frontier orbitals. Through a Principal Component Analysis (PCA) of the electron affinity, carcinogen-DNA interaction energy, electrostatic attraction and cell membrane permeability (dipole moment m and partition coefficient LogP) evidence was obtained showing carbendazim displays carcinogenic activity. For the metabolites of carbendazim, no evidence was found in the literature of their carcinogenic activities. However, the electronic parameters for these metabolites exhibited similarity to known carcinogens, thereby showing the importance of the results obtained in this study for a policy based on the precautionary principle.

A QSPR Study for the Prediction of the pKa of N-Base Ligands and Formation Constant Kc of Bis(2,2′-bipyridine)Platinum(II)-N-Base Adducts Using Quantum Mechanically Derived Descriptors

Quantitative structure-property relationship (QSPR) study on the acid dissociation constant, pKa of various 22 N-base ligands including pyridines, pyrimidines, purines, and quinolines has been carried out using Codessa Pro methodology and software. In addition, the formation constant, Kc of these ligands with Pt(II)(bpy)2 2+ (bpy = 2,2′-bipyridine) ion has also been modelled with the same methodology. Linear regression QSPR models of pKa and Kc were established with descriptors derived from AM1 calculations. Among the obtained QSPR models of pKa presented in the study, statistically the most significant one is a four parameters linear equation with the squared correlation coefficient, R2 values of ca. 0.95 and the squared cross-validated correlation coefficient, Rcv2 values of ca. 0.89, and external the squared correlation coefficient, Rext.2 values of ca. 0.97. Statistically the most significant QSPR model of Kc is also a four parameters linear equation with the squared correlation coefficient, R2 values of ca. 0.75 and the squared cross-validated correlation coefficient, Rcv2 values of ca. 0.55, and external the squared correlation coefficient, Rext.2 values of ca. 0.81. An analysis of descriptors that involved in the pKa models indicate that reactivity index and charge distribution related descriptors play major roles to model acid dissociation constant of ligands of N bases.

Fluorescent substituted amidines of benzanthrone: Synthesis, spectroscopy and quantum chemical calculations

Several new substituted amidine derivatives of benzanthrone were synthesized by a condensation reaction from 3-aminobenzo[de]anthracen-7-one and appropriate aromatic and aliphatic amides. The obtained derivatives have a bright yellow or orange fluorescence in organic solvents and in solid state. The novel benzanthrone derivatives were characterized by TLC analysis, 1H NMR, IR, MS, UV/vis, and fluorescence spectroscopy. The solvent effect on photophysical behaviors of these dyes was investigated, and the results showed that the Stoke’s shift increased, whereas quantum yield decreased with the growth of the solvent polarity. The structure of some dyes was confirmed by the X-ray single crystal structure analysis. AM1, ZINDO/S and ab initio calculations using Gaussian software were carried out to estimate the electron system of structures. The calculations show planar configurations for the aromatic core of these compounds and two possible orientations of amidine substituents. The calculation results correlate well with red-shifted absorption and emission spectra of compounds.

Synthesis, crystal structure and rearrangements of orthocyclophane cyclotetraveratrylene (CTTV) tetraketone

Oxidation of cyclotetraveratrylene (CTTV) with potassium permanganate in pyridine under reflux gave tetraketone (the [14]ketonand) 3 which exists as a previously unobserved barrel conformation with S4 symmetry in the crystal structure, although the more familiar ‘boat’ conformer was shown by semi-empirical AM1 calculations to be 3.03 kcal/mol lower in energy. In addition to CTTV tetraketone 3, an isomeric bis-spirolactone 4 was isolated from the basic oxidation conditions, analogous to the product of trans-annular attack and rearrangement observed with oxidation of cyclotriveratrylene, whereas in acid at elevated temperatures, tetraketone 3 underwent a very efficient rearrangement and decarboxylation to afford the highly symmetric spirobi[anthracene]-10,10′-dione derivative 5.

Fluorescence Quenching Reaction of Fenaminosulf with Acriflavine and Their Analytical Applications

In pH=5.4 Britton-Robinson(BR) buffer solution,fenaminosulf(FM) reacted with acriflavine(AF) to form an ion associated complex,which resulted in the quench of the fluorescences of acriflavine.The maximum excitation wavelength(λex) and emission wavelength(λem) was located at 451 nm and 508 nm.The quenching value(ΔF) was linear to the concentration of FM in the range of 0.16~5.0 mg/L with the detection of limit(3σ) of 0.048 mg/L.Therefore,a simple,rapid,highly sensitive and selective method for the determination of FM by fluorescence quenching had been established.The proposed method had been used to determine FM in fenaminosulf pesticide and soil residue with satisfactory results.In addition,the fluorescence characters of the reaction system and the mechanism of fluorescence quenching were also discussed by AM1 calculations.

Photophysical properties and estimation of ground and excited state dipole moments of 7-diethylamino and 7-diethylamino-4-methyl coumarin dyes from absorption and emission spectra

In the present work, the effect of solvents on absorption and fluorescence spectra and dipole moments ( μ g , μ e ) of 7-diethylamino coumarin (7DEAC) and 7-diethylamino-4-methyl coumarin (7DEA4MC) have been studied in different solvents of various polarity at room temperature. The solvents have been selected in a way to cover the full range of intermolecular interactions from non-polar hexane to strongly polar formamide. Using the methods of solvatochromism, the difference in the first excited singlet-state ( μ e ) and ground state ( μ g ) dipole moments was estimated from Lippert-Mataga, Bakhshiev, Kawski-Chamma-Viallet and McRae equations. The Onsager’s cavity radius of the probes has been calculated by AM1 and PM3 quantum chemical calculations and also by a direct relation. The change in dipole moment value (Δ μ ) was also calculated by using the variation of Stoke’s shift with microscopic solvent polarity parameter ( E T N ). The calculated dipole moments represent new results, as well as some of the solvatochromic results that were not studied earlier in such large number of solvents. It is observed that the values of excited singlet-state dipole moments are higher than the ground state ones in both the molecules, which shows that excited states are more polar than the ground states.

Towards rational molecular design for reduced chronic aquatic toxicity

The routine rational design of commercial chemicals with minimal toxicological hazard to humans and the environment is a key goal of green chemistry. The development of such a design strategy requires an understanding of the interrelationships between physical–chemical properties, structure, mechanisms and modes of action. This study develops property-based guidelines for the design of chemicals with reduced chronic aquatic toxicity to multiple standardized species and endpoints by exploring properties associated with bioavailability, narcotic toxicity and reactive modes of action, such as electrophilic interactions. Two simple properties emerge as key parameters that distinguish chemicals in the Low EPA level of concern to three aquatic species from those in the High level of concern – octanol–water partition coefficient, (log Po–w) and ΔE (LUMO–HOMO energy gap). Physicochemical properties were predicted using Schrodinger's QikProp, while frontier orbital energies were determined based on AM1 and DFT calculations using Gaussian03. Experimental toxicity data used consisted of chronic toxicity thresholds (NOEC) for Daphnia magna reproduction (317 compounds, 504 h-assay) and Oryzias latipes (Japanese medaka, 122 compounds in 336, 504 and 672 h assays) survival, and Pseudokirchneriella subcapitata, a green algae model (392 compounds). Results indicate that 92% of compounds of Low chronic concern have log Po–w values 9 eV. Chronically safe compounds to P. subcapitata meet similar criteria – 80% have log Po–w values < 3 and ΔE greater than 9 eV. Our work proposes design guidelines that can be used to significantly increase the probability that a chemical will have low chronic toxicity, based on the endpoints evaluated, to the three diverse aquatic species studied, and potentially to other aquatic species.