Density Functional Theory Geometry Research Articles

Zinc isotope fractionation during coprecipitation with amorphous iron (hydr)oxides

Coprecipitation facilitates the incorporation of Zn into the lattice of Fe (hydr)oxide, which is a crucial mechanism causing low Zn bioavailability in widespread Zn-deficient soils. Zn isotopes are a potential indicator of the coprecipitation of Zn and Fe (hydr)oxides in soils. However, the Zn isotope fractionation caused by coprecipitation with amorphous Fe (hydr)oxides (e.g., ferrihydrite) and the impact of environmentally relevant conditions remain unknown. Here, the molecular mechanism and impact factor of Zn isotope fractionation during Zn2+-Fe3+ coprecipitation under natural soil conditions (including different pH values and initial Zn/Fe ratios) were investigated by combining isotope ratio measurements, extended X-ray absorption fine structure (EXAFS) analyses, and density functional theory (DFT) geometry optimization. The results show that aqueous Zn (Znaq) can be complexed on the ferrihydrite surface (Znads) with positive isotope fractionation (Δ66Znads–aq = 0.42 ± 0.09 ‰) or directly incorporated into the ferrihydrite lattice with slightly negative isotope fractionation (Δ66Znstru-aq = −0.08 ± 0.03 ‰). In addition, over time, the surface-complexed Zn can further transform to a layered structure on the surface but exhibits limited Zn isotope fractionation. According to Zn K-edge EXAFS, the Zn isotope fractionation of surface complexation and incorporation of Znaq are related to the decrease in the Zn–O bond strength in the order surface complexed Zn (RZn–O = 2.00 Å) > aqueous Zn (RZn–O = 2.08 Å) > directly incorporated Zn (RZn–O = 2.06–2.07 Å with slight distortion). The limited Zn isotope fractionation associated with the transformation of Znads is related to the reconfiguration of Znads during the nucleation of octahedral Zn layer structures. Furthermore, the primary process controlling Zn isotope fractionation is different under varying experimental conditions, leading to distinct Zn isotope fractionation between the bulk solid and solution during Zn–Fe coprecipitation. Low pH values (5.0–6.0) and initial Zn/Fe ratios (0.01–0.02) favor the direct precipitation of Znaq, resulting in slightly negative Zn isotope fractionation between the bulk solid and solution. In contrast, high pH values (7.0–7.5) and initial Zn/Fe ratios (0.1–0.2) favor surface complexation and the transformation of Znads, leading to heavy Zn isotope enrichment in the bulk solid. These findings offer novel insights into the primary mechanism through which Fe (hydr)oxides regulate Zn bioavailability in Zn-deficient soils and provide experimental evidence supporting the potential application of Zn isotopes as an indicator for comprehending the fate of Zn controlled by Fe (hydr)oxides in soils.

Molecular Geometry Impact on Deep Learning Predictions of Inverted Singlet-Triplet Gaps.

We present a deep learning model able to predict excited singlet-triplet gaps with a mean absolute error (MAE) of ≈20 meV to obtain potential inverted singlet-triplet (IST) candidates. We exploit cutting-edge spherical message passing graph neural networks designed specifically for generating 3D graph representations in molecular learning. In a nutshell, the model takes as input a list of unsaturated heavy atom Cartesian coordinates and atomic numbers, producing singlet-triplet gaps as output. We exploited available large data collections to train the model on ≈40,000 heterogeneous density functional theory (DFT) geometries with available ADC(2)/cc-pVDZ singlet-triplet gaps. We ascertain the predictive power of the model from a quantitative perspective obtaining predictions on a test set of ≈14,000 molecules, whose geometries have been generated at DFT level (the same employed for the geometries in the training set), at GFN2-xTB level, and through Molecular Mechanics. We notice performance degradation upon switching to lower-quality geometries, with GFN2-xTB ones maintaining satisfactory results (MAE ≈ 50 meV on GFN2-xTB geometries, MAE ≈ 180 meV on generalized AMBER force field geometries), hinting at caution when dealing with specific chemical classes. Finally, we verify the performance of the model from the qualitative point of view, obtaining predictions on a different data set of ≈15,000 molecules already used to identify new IST molecules. We obtained predictions using both DFT and experimental X-ray geometries, with results on IST candidates similar to those provided by quantum chemical methods, with clear hints for the path toward improved performance.

Theoretical Investigation of Linear Relationships between the Dihedral Torsion Angles and Diosmium Bond Distances in Diosmium Sawhorse Complexes.

Strong linear relationships between their Ceq-Os-Os-Ceq dihedral angles and their Os-Os bond distances in diosmium sawhorse complexes Os2(u-O2CR)2(CO)4L2 (L = CO and/or PR3) form two trendlines depending upon the presence or absence of terminal phosphines. These trends appear unrelated to the basicity of the bridging ligand or the number of phosphines. The mathematical derivation of the relationship between the O-Os-Os-O dihedral angle and the Os-Os bond distance shows how the other geometric parameters affect this relationship. Optimized density functional theory (DFT) structures reveal a similar strong linear correlation, where more electron-donating ligands render shorter Os-Os bond distances and larger dihedral angles, but these results form a single trendline. Computational scans of individual parameters show that the Os-Os bond responds strongly to changes in the dihedral angles, but the dihedral angles only respond weakly to changes in the Os-Os bond distance because the Os-Os-O bond angle links and modifies their direct coupling. Solid-state analysis of their structures, including DFT geometry optimizations, shows that phosphines protect the Os-Os bond distance from packing influences along the Os-Os axis, while in complexes without phosphines, packing compresses the Os-Os bond and the weak dihedral responses create the second trendline.

Heterobimetallic Fe(II)–Cu(I) Complexes Supported with 1,1′-Bis(diphenylphosphino)ferrocene and Chelating Sulfur Donor Ligands: Structural Characterization, DFT Analysis, Anti-tyrosinase Assay and Biological Studies

Heterobimetallic complexes [(dppf)CuSP(S)(OiPr)2] (1), [(dppf)CuSP(S)(OEt)2] (2), [(dppf)CuSP(S)(OCy)2] (3) and [(dppf)CuS2H2B(mt)2] (4), supported with sulfur donors from the family of dialkyldithiophosphate, SP(S)(OR)2 (R = iPr, Et, Cy) and borate ligands, (S)2H2B(mt)2, were synthesized in one pot by the reaction of 1,1′-Bis(diphenylphosphino)ferrocene (dppf) with [Cu(CH3CN)4]BF4 and subsequent addition of the chelating sulfur donor ligands at room temperature in an overall moderate yield. 1-4 were characterized using a combination of 1H, 13C{1H}, 31P{1H} NMR, IR spectroscopy techniques, and single crystal X-ray diffraction. Crystal structure analysis revealed that Cu(I) centers in 1-4 adopt a distorted tetrahedral geometry. The borate ligand in 4 adopts a κ3-S,S,H mode in the solid state. A density functional theory geometry optimization calculation was used to extract further structural and electronic information about 1-4. To investigate the possible cytotoxicity of 1-4, in vitro cellular tests were carried out on the human cancerous breast cell line MCF-7. The antibacterial activities of complexes 1 and 4 were screened against gram-positive Staphylococcus aureus PTCC 1112 and gram-negative Escherichia coli PTCC 1330.

PCS/Bonds and PCS0: Pick your molecule and get its accurate structure and ground state rotational constants at DFT cost.

An unsupervised computational protocol is proposed with the aim of obtaining accurate structures of large molecules in the gas phase at the cost of standard density functional theory (DFT) computations. The whole workflow is fully automated and provides optimized equilibrium geometries and ground state rotational constants to be directly compared with experiments. The results for a panel of molecules of biological or medicinal interest show that the accuracy of the results delivered by the new tool at the cost of a single DFT geometry optimization is close to that delivered by state-of-the-art composite wavefunction methods for small semi-rigid molecules.

Molecular Geometries and Vibrational Contributions to Reaction Thermochemistry Are Surprisingly Insensitive to the Choice of Basis Sets.

Calculation of molecular geometries and harmonic vibrational frequencies are pre-requisites for thermochemistry calculations. Contrary to conventional wisdom, this paper demonstrates that quantum chemical predictions of the thermochemistry of many gas and solution phase chemical reactions appear to be very insensitive to the choice of basis sets. For a large test set of 80 diverse organic and transition-metal-containing reactions, variations in reaction free energy based on geometries and frequencies calculated using a variety of double and triple-zeta basis sets from the Pople, Jensen, Ahlrichs, and Dunning families are typically less than 4 kJ mol-1, especially when the quasiharmonic oscillator correction is applied to mitigate the effects of low-frequency modes. Our analysis indicates that for many organic molecules and their transition states, high-level revDSD-PBEP86-D4 and DLPNO-CCSD(T)/(aug-)cc-pVTZ single-point energies usually vary by less than 2 kJ mol-1 on density functional theory geometries optimized using basis sets ranging from 6-31+G(d) to aug-pcseg-2 and aug-cc-pVTZ. In cases where these single-point energies vary significantly, indicating sensitivity of molecular geometries to the choice of basis set, there is often substantial cancellation of errors when the reaction energy or barrier is calculated. The study concludes that the choice of basis set for molecular geometry and frequencies, particularly those considered in this study, is not critical for the accuracy of thermochemistry calculations in the gas or solution phase.

Two local minima for structures of [4Fe–4S] clusters obtained with density functional theory methods

[4Fe–4S] clusters are essential cofactors in many proteins involved in biological redox-active processes. Density functional theory (DFT) methods are widely used to study these clusters. Previous investigations have indicated that there exist two local minima for these clusters in proteins. We perform a detailed study of these minima in five proteins and two oxidation states, using combined quantum mechanical and molecular mechanical (QM/MM) methods. We show that one local minimum (L state) has longer Fe–Fe distances than the other (S state), and that the L state is more stable for all cases studied. We also show that some DFT methods may only obtain the L state, while others may obtain both states. Our work provides new insights into the structural diversity and stability of [4Fe–4S] clusters in proteins, and highlights the importance of reliable DFT methods and geometry optimization. We recommend r2SCAN for optimizing [4Fe-4S] clusters in proteins, which gives the most accurate structures for the five proteins studied.

Homobimetallic Au(I)-Au(I) and Heterotrimetallic Au(I)-Fe(II)-Au(I) Complexes with Dialkyldithiophosphates and Phosphine Ligands: Structural Characterization, DFT Analysis, and Tyrosinase Inhibitory and Biological Effects.

The role of bridging and terminal ligand electronic and steric properties on the structure and antiproliferative activity of two-coordinated gold(I) complexes was investigated on seven novel binuclear and trinuclear gold(I) complexes synthesized by the reaction of either Au2(dppm)Cl2, Au2(dppe)Cl2, or Au2(dppf)Cl2 with potassium diisopropyldithiophosphate, K[(S-OiPr)2], potassium dicyclohexyldithiophosphate, K[(S-OCy)2], or sodium bis(methimazolyl)borate, Na(S-Mt)2, which afforded air-stable gold(I) complexes. In 1-7, the gold(I) centers adopt a two-coordinated linear geometry and are structurally similar. However, their structural features and antiproliferative properties highly depend upon subtle ligand substituent changes. All complexes were validated by 1H, 13C{1H}, 31P NMR, and IR spectroscopy. The solid-state structures of 1, 2, 3, 6, and 7 were confirmed using single-crystal X-ray diffraction. A density functional theory geometry optimization calculation was used to extract further structural and electronic information. To investigate the possible cytotoxicities of 2, 3, and 7, in vitro cellular tests were carried out on the human cancerous breast cell line MCF-7. 2 and 7 show promising cytotoxicity.

Binding profile of a mixed-ligand silver(I) complex with DNA and Topoisomerase I

A new mixed-ligand Ag(I) complex, [Ag(daf)(phen)]NO3 (daf = 4,5-diazafluoren-9-one and dian = N-(4,5-diazafluoren-9-ylidene)aniline), was synthesized. The elemental analysis, FTIR, 1HNMR, UV–Vis spectroscopy, cyclic voltammetry, and DFT (Density Functional Theory) geometry optimization method were applied in order to predict the Ag(I) complex structure which concluded to a distorted tetrahedral N4 coordination around the Ag(I) center. A detailed in silico analysis of the bioaffinity of the complex to DNA and human DNA-Topoisomerase I was conducted using molecular docking simulations and ONIOM (Our own N-layered Integrated molecular Orbital and molecular Mechanics) techniques. In this overall scenario, the results suggest the dominance of π-π stacking interactions of the heteroaromatic ligands in the intercalating pocket of DNA and the active site of the enzyme and the rational correlation between being a good intercalator and a potent Topoisomerase I inhibitor. In vitro DNA-binding experiments by spectrophotometric, spectrofluorometric, Voltammetric, and viscometric techniques at physiological pH also confirmed the computational results. The complex inhibited MCF-7 cell growth in a dose-dependent manner while being nontoxic on HUVEC normal cells.

Importance of Precursor Adaptability in the Assembly of Molecular Organic Cages

For molecular architectures based on dynamic covalent chemistry (DCvC), strict preorganization is a paradigmatic concept and the generally accepted strategy for their rational design. This results in the creation of highly rigid building blocks which are expected to fulfill the ideal geometry of the assembly, coming at a price that small geometric mismatches result in unpredicted and/or unproductive reaction outcomes. In this study, we show that feet of a tripodal platform have a great influence on the assembly of tetrahedral organic cages based on boronate ester formation. The aryl benzyl ether-functionalized building blocks perform significantly better than their alkyl-functionalized equivalents. Experimentally and using density functional theory geometry optimization of the cage structures, we prove that unexpectedly, this is not due to solubility but because of the enhanced capability of the aryl benzyl ether-functionalized building blocks to fit the ideal geometry of the assembly. This introduces the concept of building block adaptability to overcome geometrical mismatches in DCvC systems.

Prediction of the structures and heats of formation of MO2, MO3, and M2O5 for M = V, Nb, Ta, Pa.

Structures for the mono-, di-, and tri-bridge isomers of M2O5 as well as those for the MO2 and MO3 fragments for M = V, Nb, Ta, and Pa were optimized at the density functional theory (DFT) level. Single point CCSD(T) calculations extrapolated to the complete basis set (CBS) limit at the DFT geometries were used to predict the energetics. The lowest energy dimer isomer was the di-bridge for M = V and Nb and the tri-bridge for M = Ta and Pa. The di-bridge isomers were predicted to be composed of MO2+ and MO3- fragments, whereas the mono- and tri-bridge are two MO2+ fragments linked by an O2-. The heats of formation of M2O5 dimers, as well as MO2 and MO3 neutral and ionic species were predicted using the Feller-Peterson-Dixon (FPD) approach. The heats of formation of the MF5 species were calculated to provide additional benchmarks. Dimerization energies to form the M2O5 dimers are predicted to become more negative going down group 5 and range from -29 to -45 kcal mol-1. The ionization energies (IEs) for VO2 and TaO2 are essentially the same at 8.75 eV whereas the IEs for NbO2 and PaO2 are 8.10 and 6.25 eV, respectively. The predicted adiabatic electron affinities (AEAs) range from 3.75 eV to 4.45 eV for the MO3 species and vertical detachment energies from 4.21 to 4.59 eV for MO3-. The calculated MO bond dissociation energies increase from 143 kcal mol-1 for M = V to ∼170 kcal mol-1 for M = Nb and Ta to ∼200 kcal mol-1 for M = Pa. The M-O bond dissociation energies are all similar ranging from 97 to 107 kcal mol-1. Natural bond analysis provided insights into the types of chemical bonds in terms of their ionic character. Pa2O5 is predicted to behave like an actinyl species dominated by the interactions of approximately linear PaO2+ groups.

How does multi-reference computation change the catalysis chemistry? DFT and CASPT2 studies of the Cu-catalysed coupling reactions between aryl iodides and β-diketones.

The molecular mechanism of a Cu-catalysed coupling reaction was theoretically studied using density functional theory (DFT) and the complete active space self-consistent field method followed by the second-order perturbation theory (CASSCF/CASPT2) to investigate the effects of the strong electron correlation of the Cu centre on the reaction profile. Both DFT and CASSCF/CASPT2 calculations showed that the catalytic cycle proceeds via an oxidative addition (OA) reaction, followed by a reductive elimination (RE) reaction, where OA is the rate-determining step. Although the DFT-calculated activation energies of the OA and RE steps are highly dependent on the choice of functionals, the CASSCF/CASPT2 results are less affected by the choice of DFT-optimised geometries. Therefore, with a careful assessment based on the CASSCF/CASPT2 single-point energy evaluation, an optimal choice of the DFT geometry is of good qualitative use for energetics at the CASPT2 level of theory. Based on the changes in the electron populations of the 3d orbitals during the OA and RE steps, the characteristic features of the DFT-calculated electronic structure were qualitatively consistent with those calculated using the CASSCF method. Further electronic structure analysis by the natural orbital occupancy of the CASSCF wavefunction showed that the ground state is almost single-reference in this system and the strong electron correlation effect of the Cu centre can be dealt with using the MP2 or CCSD method, too. However, the slightly smaller occupation numbers of the 3dπ orbital in the course of reactions suggested that the electron correlation effect of the Cu(III) centre appears through the interaction between the 3dπ orbital and the C-I antibonding σ* orbital in the OA step, and between the 3dπ orbital and the Cu-C antibonding σ* orbital in the RE step.

On the Origin of the Blue Color in The Iodine/Iodide/Starch Supramolecular Complex.

The nature of the blue color in the iodine-starch reaction is still a matter of debate. Some textbooks still invoke charge-transfer bands within a chain of neutral I2 molecules inside the hydrophobic channel defined by the interior of the amylose helical structure. However, the consensus is that the interior of the helix is not altogether hydrophobic-and that a mixture of I2 molecules and iodide anions reside there and are responsible for the intense charge-transfer bands that yield the blue color of the "iodine-starch complex". Indeed, iodide is a prerequisite of the reaction. However, some debate still exists regarding the nature of the iodine-iodine units inside the amylose helix. Species such as I3-, I5-, I7- etc. have been invoked. Here, we report UV-vis titration data and computational simulations using density functional theory (DFT) for the iodine/iodide chains as well as semiempirical (AM1, PM3) calculations of the amylose-iodine/iodide complexes, that (1) confirm that iodide is a pre-requisite for blue color formation in the iodine-starch system, (2) propose the nature of the complex to involve alternating sets of I2 and Ix- units, and (3) identify the nature of the charge-transfer bands as involving transfer from the Ix- σ* orbitals (HOMO) to I2 σ* LUMO orbitals. The best candidate for the "blue complex", based on DFT geometry optimizations and TD-DFT spectral simulations, is an I2-I5-I2 unit, which is expected to occur in a repetitive manner inside the amylose helix.

“On Water” Effect for Green Click Reaction: Spontaneous Polymerization of Activated Alkyne with “Inert” Aromatic Amine in Aqueous Media

“On Water” Effect for Green Click Reaction: Spontaneous Polymerization of Activated Alkyne with “Inert” Aromatic Amine in Aqueous Media

Photophysical and in vitro photoinactivation of Escherichia coli using cationic 5,10,15,20-tetra(pyridin-3-yl) porphyrin and Zn(II) derivative conjugated to graphene quantum dots

Pathogenic microorganisms may continue causing infection through the transfer of antibiotic resistance genes. As a result, the efficacy of pharmaceuticals in microbial inactivation is deteriorating. The present study was conducted to investigate the antimicrobial activity of neutral and quaternized free base and Zn 5,10,15,20-tetra(pyridin-3-yl) porphyrins on Escherichia coli (E. coli), a gram-negative bacterium that causes cholecystitis, pneumonia and urinary tract infections. Conjugation of the porphyrin to graphene quantum dots (GQDs) was implemented to enhance photocatalysis and reactive oxygen species generation. Density functional theory (DFT) geometry optimizations for free base and Zn porphyrin based on the B3LYP (Becke 3-Parameter (Exchange), Lee, Yang and Parr) functional of the Gaussian09 program package and Time-dependent density-functional theory (TD-DFT) calculations of the associated UV-visible absorption spectra are reported to analyse the electronic structure and optical properties of the porphyrins. The TD-DFT calculations showed that for both porphyrins the value of highest occupied molecular orbital (ΔHOMO) is greater than that of lowest unoccupied molecular orbital (ΔLUMO) which tells that there is no unusual splitting of (LUMO) orbitals which may be caused by systematic error in TD-DFT calculations. Due to the red shift in the spectrum of ZnT(3-Py)P and the ΔLUMO being higher, the HOMO-LUMO gap was expected to be lower than that of H2T(3-Py)P. The photophysical properties and Photodynamic antimicrobial chemotherapy activities of these nanoconjugates were investigated. The highest ΦΔ was that of Q-ZnT(3-Py)P- GDQs at 0.69 with the log reduction of 9.42.

Combined Experimental and Computational Kinetics Studies for the Atmospherically Important BrHg Radical Reacting with NO and O2.

We report on the first experimental determination of the absolute rate constant of the reaction of BrHg + NO in N2 bath gas using a laser photolysis-laser-induced fluorescence (LP-LIF) system. The rate constant of the reaction of BrHg + NO is determined to be 7.0-0.9+1.3 × 10-12 cm3 molecule-1 s-1 over 50-700 Torr and 315-353 K. The absence of a pressure or temperature dependence suggests that this reaction leads mainly to mercury reduction (Hg + BrNO) rather than mercury oxidation (BrHgNO). Our theoretical calculations using NEVPT2 energies on density functional theory (DFT) geometries are consistent with a barrierless reaction to form Hg + BrNO. The equilibrium constants and the rate constants of the reaction BrHg + O2 ⇌ BrHgOO are computed theoretically because they are too low to be measured in the LP-LIF system. Molecular oxygen quenches the LIF signal of BrHg with a large rate constant of (1.7 ± 0.1) × 10-10 cm3 molecule-1 s-1. Thus, different techniques that capture the absolute [BrHg(X̃)] would be advantageous for kinetics studies of BrHg reactions in the presence of O2. The computed equilibrium constant suggests a non-negligible upper limit of the fraction of BrHg stored as BrHgOO (up to 0.5) at low-temperature conditions, e.g., in the upper troposphere and in polar winters at ground level. Preliminary results indicate that BrHgOO behaves like HOO or organic peroxy radicals in reactions with atmospheric radicals.

Molecular insight into the simultaneous capture of sarin/soman by graphene incorporating dual metal sites

Competitive adsorption of two major Chemical Warfare agents (CWAs), soman and sarin, was explored on a multi-site embedded graphene model integrating transition metal atoms (Cr, V and Zn). Ab-initio Molecular Dynamics simulations were performed to determine the most probable configurations of these CWAs on the graphene substrate. Further Density Functional Theory geometry optimizations revealed that both soman and sarin adopt a single-adduct configuration on a metal site whatever the nature of metal pairs considered, a scenario similar to that encountered for graphene embedding only 1 metal site. This result strongly suggests that each metal site present in real activated carbons is effective for the capture of these CWAs. To understand the effect of humidity, which is a major shortcoming in the field of air protector devices, further calculations were carried out in the presence of water molecules. We demonstrated that water does not dramatically impact the strength of interactions between these CWAs and both Cr and V metals while there is a substantial drop in the case of Zn metals. This trend was explained in light of further electronic analysis. This conclusion suggests that the use of Cr or V metal enables to maintain an efficient capture of CWAs under humidity while for Zn it is far to be the case.

Effect of Synthesis Temperature on Water Adsorption in UiO-66 Derivatives: Experiment, DFT+D Modeling, and Monte Carlo Simulations

In this work, density functional theory (DFT) and Monte Carlo calculations were combined with standard volumetric adsorption as well as quasi-equilibrated temperature-programmed desorption and adsorption measurements to study water adsorption in UiO-66 derivatives containing −NH2, −NO2, and −Br substituents. Based on DFT modeling, both the position and geometry of the substituents were determined and one model was selected for each structure. By using Monte Carlo simulations and the force field developed in our previous work for the adsorption of water in metal–organic frameworks, we reproduced experimental adsorption isotherms and isobars. The results allow us to explain the water adsorption process in UiO-66 derivatives. Detailed physicochemical characterization by means of elemental analysis, powder X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis enabled us to determine the influence of the synthesis temperature on the structure and properties of the materials.

Benchmarking Semiempirical QM Methods for Calculating the Dipole Moment of Organic Molecules.

The dipole moment is a simple descriptor of the charge distribution and polarity and is important for understanding and predicting various molecular properties. Semiempirical (SE) methods offer a cost-effective way to calculate dipole moment that can be used in high-throughput screening applications although the accuracy of the methods is still in question. Therefore, we have evaluated AM1, GFN0-xTB, GFN1-xTB, GFN2-xTB, PM3, PM6, PM7, B97-3c, HF-3c, and PBEh-3c SE methods, which cover a variety of SE approximations, to directly assess the performance of SE methods in predicting molecular dipole moments and their directions using 7211 organic molecules contained in the QM7b database. We find that B97-3c and PBEh-3c perform best against coupled-cluster reference values yielding dipole moments with a mean absolute error (MAE) of 0.10 and 0.11 D, respectively, which is similar to the MAE of density functional theory (DFT) methods (∼0.1 D) reported earlier. Analysis of the atomic composition shows that all SE methods show good performance for hydrocarbons for which the spread of error was within 1 D of the reference data, while the worst performances are for sulfur-containing compounds for which only B97-3c and PBEh-3c show acceptable performance. We also evaluate the effect of SE optimized geometry, instead of the benchmark DFT geometry, that shows a dramatic drop in the performance of AM1 and PM3 for which the range of error tripled. Based on our overall findings, we highlight that there is an optimal compromise between accuracy and computational cost using GFN2-xTB (MAE: 0.25 D) that is 3 orders of magnitude faster than B97-3c and PBEh-3c. Thus, we recommend using GFN2-xTB for cost-efficient calculation of the dipole moment of organic molecules containing C, H, O, and N atoms, whereas, for sulfur-containing organic molecules, we suggest PBEh-3c.

Microwave-assisted N-alkylation of amines with alcohols catalyzed by MnCl2 : Anticancer, docking, and DFT studies.

A new protocol for the N-alkylation of amines with alcohols for the synthesis of tertiary amines in the presence of MnCl2 as a catalyst, under microwave conditions, is described. The advantages of this protocol include stable reaction profiles, a wide substrate variety, excellent yields, low cost, high yields, and easy workup conditions. The anticancer efficacy of all the synthesized compounds was tested in vitro against various cancer cell lines, such as MCF-7, MDA-MB-231 (human breast), HT-29, HCT 116 (colon cancer), A549 (human lung carcinoma), and Vero cells. Among the screened compounds, 3e, 3h, and 3i demonstrated potent anticancer activity, with compound 3h surpassing the reference drug cisplatin against A549, MCF7, MDA-MB-231, and HCT116 cancer cells. The introduction of an electron-withdrawing group on the phenyl ring resulted in increased anticancer activity. The most potent compounds, 3e, 3h, and 3i, were tested against VEGFR-2, HER2, and EGFR in multikinase inhibition assays, with compounds 3h and 3i showing improved potency against the HER2 kinase. The compounds formed two H-bonds with amino acids, indicating that they had a high affinity for the target HER2 kinase (PDB ID: 3RCD), according to the docking analysis. The absorption, distribution, metabolism, excretion, and toxicity properties of the optimized analogs were also assessed in vitro, enabling the discovery of promising anticancer agents. Finally, the B3LYP level was used to measure density functional theory geometry optimization and the related quantum parameters for the active compounds.