Topological Analysis Of Electron Density Research Articles

Machine learning-based prediction of bioactivity in HIV-1 protease: insights from electron density analysis.

Aim: To develop a model for predicting the biological activity of compounds targeting the HIV-1 protease and to establish factors influencing enzyme inhibition.Materials & methods: Machine learning models were built based on a combination of Richard Bader's theory of Atoms in Molecules and topological analysis of electron density using experimental x-ray 'protein-ligand' complexes and inhibition constants data.Results & conclusion: Among all the models tested, logistic regression achieved the highest accuracy of 0.76 on the test set. The model's ability to differentiate between less active and highly active classes was relatively good, as indicated by an AUC-ROC score of 0.77. The analysis identified several critical factors affecting the biological activity of HIV-1 protease inhibitors, including the electron density contribution of hydrogen atoms, bond-critical points and particular amino acid residues. These findings provide new insights into how these molecular factors influence HIV-1 protease inhibition, emphasizing the importance of hydrogen bonding, glycine's flexibility and hydrophobic interactions in ligand binding.

Mechanical Tuning of Fluorescence Lifetime and Bandgap in an Elastically Flexible Molecular Semiconductor Crystal.

Despite having superior transport properties, lack of mechanical flexibility is a major drawback of crystalline molecular semiconductors as compared to their polymer analogues. Here single crystals of an organic semiconductor are reported that are not only flexible but exhibit systematic tuning of bandgaps, fluorescence lifetime, and emission wavelengths upon elastically bending. Spatially resolved fluorescence lifetime imaging and confocal fluorescence microscopy reveals systematic trends in the lifetime decay across the bent crystal region along with shifts in the emission wavelength. From the outer arc to the inner arc of the bent crystal, a significant decrease in the lifetime of ≈1.9ns is observed, with a gradual bathochromic shift of ≈10nm in the emission wavelength. For the crystal having a bandgap of 2.73eV, the directional stress arising from bending leads to molecular reorientation effects and variations in the extent of intermolecular interactions- which are correlated to the lowering of bandgap and the evolution of the projected density of states. The systematic changes in the interactions quantified using electron density topological analysis in the compressed inner arc and elongated outer arc region are correlated to the non-radiative decay processes, thus rationalizing the tuning of fluorescence lifetime.

Molecular Tailoring Approach for the Direct Estimation of Individual Noncovalent Interaction Energies in Molecular Systems.

The noncovalent interactions (NCIs) are omnipresent in chemistry, physics, and biology. The study of such interactions offers insights into various physicochemical phenomena. Some indirect approaches proposed in the literature for exploring the NCIs are briefly reviewed in Section 1 of this Perspective. These include: (i) Shift in the stretching frequency of an X-Y bond involved in X-Y···Z interaction. (ii) Topological analysis of molecular electron density. (iii) Empirical equations derived employing experimental and theoretical quantities. However, a direct method for estimating individual intramolecular/intermolecular interaction energies has been conspicuous by its absence from the literature. We have developed a molecular tailoring approach (MTA)-based method enabling a direct and reliable estimation of the energy of intra- as well as intermolecular interactions. This method offers a direct and reliable estimation of these interactions, in particular of the hydrogen bonds (HB) in molecules/weakly bound clusters along with the respective cooperativity contribution. In Section 2, the basis of our method is discussed, along with some illustrative examples. The application of this method to a variety of molecules and clusters, with a special emphasis on estimating the HB energy along with the energy of other NCIs is presented in Section 3. Section 4 discusses some computational strategies for applying our method to large molecular clusters. The last Section provides a summary and a discussion on future developments.

DFT study on the Stereoselectivity of Asymmetric Synthesis of C, N‐Cyclic Azomethine Imines with Allyl Alkyl Ketones

AbstractBased on the density functional theory, the stereoselectivity of the asymmetric synthesis of tetrahydroisoquinolinopyrazole derivatives by the cycloaddition reaction of C, N‐cyclic azomethine imines with allyl alkyl ketones which was catalyzed using a chiral primary amine is studied theoretically. The results demonstrate that the four chiral transition states (TS‐1R2R, TS‐1R2S, TS‐1S2R and TS‐1S2S) are formed by the reaction of dienamine intermediate with C, N‐cyclic azomethine imine, and the reaction barrier of TS‐1R2S is in the lowest level (ΔG=6.98 kcal/mol). The consequence reveal that the 1R2S configuration product is formed by TS‐1R2S transition state. Non‐covalent interaction and electron density topology analysis show that the stereoselectivity of the chiral product is determined through van der Waals forces and hydrogen bond interaction of the transition state molecules.

Vibrational spectra, molecular structure, electronic, pharmaceutical and bonding nature of (4S)-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7,8-diol - anti hypertension agent

Several factors, including environment, behaviours, and heredity, influence the development of hypertension. The title compound dopamine D1 receptor agonist named (4S)-4-(3,4-dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline-7,8-diol (4S4D4T) is one of the most important neurotransmitters associated with numerous neural disorders. Using DFT and quantum chemical simulations, the vibrational, electrical, and structural possessions of the heading compound were predicted. To carry out the quantum computational investigations, a highly compatible method entitled B3LYP basis set was adopted. Vibrational Modes of functional groups with PED values were calculated using VEDA software to compute geometric dimensions and assign fundamental vibrations. Using gas and solvent phases, MEP differentiates between nucleophilic and electrophilic sites and creates distribution for the charge of the molecules. The observed wavelength with (TDSCF) UV–Vis spectra for the various solvents phases were compared. The NBO approach provides an understanding of the electron delocalization that results from hyperconjugation. FUKUI analysis is used to determine the area of site reaction. Electron density's topological analysis was carried out using the QTAIM theory. The ADME (Absorption, Distribution, Metabolism, Excretion) profiles are produced with the Swiss ADME online tool. In summary, this dissertation offers a thorough examination that evaluates the impact of particular pharmaceuticals on solvation and enzyme efficiency using a combination of spectral and quantitative computing methodologies. Therefore, plans for further research can profit immensely by the information gathered. The results of protein-ligand docking using the Auto Dock method with various proteins suggest that the molecule has pharmaceutical properties against receptors.

Probing microhydration-induced effects on carbonyl compounds.

Characterizing the microhydration of organic molecules is a crucial step in understanding many phenomena relevant to atmospheric, biological, and industrial applications. However, its precise experimental and theoretical description remains a challenge. For four organic solutes containing a CO bond, and included in the recent HyDRA challenge [T. L. Fischer, M. Bödecker, A. Zehnacker-Rentien, R. A. Mata and M. A. Suhm, Phys. Chem. Chem. Phys., 2022, 24, 11442-11454.], we performed a detailed study of different monohydrate isomers and their properties; these were cyclooctanone (CON), 1,3-dimethyl-2-imidazolidinon (DMI), methyl lactate (MLA), and 2,2,2-trifluoroacetophenone (TPH) molecules. As reported in the literature, the O-H elongation shift of the water molecule appears to be a good candidate for characterizing complexation-induced effects. We also show that CO elongation shift and UV-vis spectroscopy can be successfully used for these purposes. Besides, we present a comparative analysis of the strengths of non-covalent interactions within these monohydrated complexes based on interpretative tools of quantum chemistry, including topological analysis of electron density (ρ), topological analysis of electron pairing function, and analysis of the core-valence bifurcation index (CVBI), which exhibits a close linear dependency on ρ. Accordingly, a classification of intermolecular water-solute interactions is proposed.

The cyanide, cyanate, thiocyanate ambident anions: Structure, topological analysis of electron density, and homolytic oxidative coupling regioselectivity

At the B3LYP/6-311++G(3df,3pd) level of theory, the spatial and electronic structure of the cyanide, cyanate and thiocyanate ambident anions has been studied. By means of the natural bond orbital (NBO) analysis and the R. F. W. Bader?s quantum theory ?Atoms in Molecules? (QTAIM), the electron density delocalization and topological properties in the above anions have been investigated. The distribution of electron density (NBO, QTAIM) in the XCN- (X = O, S) anions is reflected by the scheme [X-?C=?N]-. The relative contribution of the hypothetical structure X=C=N- to the resonance hybrid -X?C?N ?X=C=N- is higher in the case of X = O. The degree of the C?N or C=?N bond triple character and bond strength changes in the following series of anions: CN- > SCN- > OCN-. The occupancy of the lone electron pair (LP) orbital of the nitrogen atom in the above anions is close to 2, and the LP orbital is sp-hybridized. Condensed K. Fukui functions for the electrophilic attack have been evaluated. Local hardness of the donor reaction centres: N > C (CN-), O > N (OCN-), N > S (SCN-). The regioselectivity of the homolytic oxidative coupling reactions of CN-, OCN-, SCN- has been substantiated.

The effect of second coordination sphere interactions on the magnetic anisotropy of transition metals.

In the study of mononuclear transition metal single molecule magnets (SMMs), extensive research has concentrated on identifying optimal coordination geometries around the central metal ion to enhance SMM properties. However, the role of non-covalent interactions in the second coordination sphere has been relatively underexplored. Here, we study the impact of non-covalent Cl⋯H interactions on the magnetic anisotropy of the central Co(II) ion in the distorted axially compressed octahedral complex CoCl2(tu)4 (1) (tu = SC(NH2)2). By performing cantilever torque magnetometry on 1, the orientation of the magnetic easy axis is found to deviate by almost 40° from the axial Co-Cl bond. Theoretical modelling on structural modifications of the structure of 1, quantifies how the distance between the Cl ligand and the nearest H-atom significantly influences the orientation of the magnetic easy axis and the D-value. Experimental chemical bonding analysis based on multipole modelling of synchrotron X-ray diffraction data on 1 reveal that the nearby H-atoms polarize the electron density of the Cl-ligands. This polarization results in reduced electron density at the axial positions on the Co octahedra, explaining the calculated increase in the magnitude of the D-value, when the H-atoms are moved away from Cl in silico. Topological analysis of theoretical electron densities on modified structures of 1 corroborates an increase in the electron density at the Co-Cl bond critical point, as the nearby H-atoms are moved further from Cl. These findings demonstrate the significant influence that non-covalent interactions have on the magnetic anisotropy of mononuclear transition metals and opens the possibility of utilizing these interactions in the design of transition metal based SMMs.

Structure, stability and reactivity of inverse sandwich complexes M‐Be3‐M and M‐Zn3‐M (M = Li, Na, K, Cu, Ag, Au)

AbstractQuantum chemical calculations have b‐een carried out on the inverse sandwich type complexes formed between coinage and alkali metals with Be3 and Zn3 rings. Calculations reveal that the complexes are stable toward dissociation. Their Lewis acidic character has been evaluated using fluoride ion affinity (FIA) calculation, which reveals their strong acidic character. Topological analysis of electron density has also been performed to investigate the nature of the bond between the metal and the fluoride ion. Calculations reveal non covalent nature in case of alkali series and covalent nature in case of coinage metal series.

SYNTHESIS AND FEATURES OF THE MOLECULAR AND CRYSTAL STRUCTURE OF THE Cp4Ru4(µ3-CO)4 CLUSTER

When preparing the ruthenium dimer [Ru(CO)2Cp]2 in the thermal reaction of cyclopentadiene with Ru3(CO)12, the tetranuclear cluster [Ru(μ3-CO)Cp]4 (I) was obtained as a minor product. Spectral (13C and 1H NMR, IR) and structural studies were carried out for cluster I. By crystallization under different conditions, two types of dark cherry crystals were obtained, cluster I itself (crystal 1) and its tetrahydrate (crystal 2), the structure of which was determined by X-ray diffraction. Structural data for 1 and 2 have been deposited in the Cambridge Structural Data Center (CCDC nos. 2241197 and 2241199, respectively; deposit@ccdc.cam.ac.uk; http://www.ccdc.cam.ac.uk). Based on a comparative analysis of cluster geometry, it is shown that the distortion of the Ru4(CO)4 framework in I from ideal Td symmetry in the structure of a pure compound is determined by the anisotropy of intermolecular contacts in the crystal. Features of chemical bonding in the [Ru(μ3-CO)Cp]4 cluster and its iron-containing analogue were studied using DFT calculations using topological analysis of electron density to compare energy characteristics and effective force constant bonding interactions. The necessity of using criteria for elastic deformations of interatomic interactions (force constants) for the correct description of structural and chemical phenomena, for example, such as the structural non-rigidity of the framework of transition metal clusters, has been demonstrated.

B-carboranyl methyl thioether ligands in coordination with the W(CO)5 fragment

Complexation of B-closo- and nido-carboranyl methyl thioethers with the pentacarbonyltungsten fragment was studied. An unusual instability of the nido-derivative is detected and rationalized by means of the quantum chemical calculations followed by the topological analysis of electron density and the Interacting Quantum Atoms analysis. The structure of {(CO)5W[9-MeS-1,2-C2B10H11-κ1-S(1)]} was determined by single crystal X-ray diffraction.

Halogen Bond-Involving Self-Assembly of Iodonium Carboxylates: Adding a Dimension to Supramolecular Architecture.

We designed 0D, 1D, and 2D supramolecular assemblies made of diaryliodonium salts (functioning as double σ-hole donors) and carboxylates (as σ-hole acceptors). The association was based on two charge-supported halogen bonds (XB), which occurred between IIII sites of the iodonium cations and the carboxylate anions. The sequential introduction of the carboxylic groups in the aryl ring of the benzoic acid added a dimension to the 0D supramolecular organization of the benzoate, which furnished 1D-chained and 2D-layered structures when terephthalate and trimesate anions, correspondingly, were applied as XB acceptors. The structure-directing XB were studied using DFT calculations under periodic boundary conditions and were followed by the one-electron-potential analysis and the Bader atoms-in-molecules topological analysis of electron density. These theoretical methods confirmed the existence of the XB and verified the philicities of the interaction partners in the designed solid-state structures.

Organometallic Allene [(μ-C)(Fe(CO)4 )2 ]: Bridging Carbon Showing Transformation from Classical Electron-Sharing Bonding to Double σ-Donor and Double π-Acceptor Ligation.

Allenes (R2 C=C=CR2 ) have been traditionally perceived to feature localized orthogonal π-bonds between the carbon centres. We have carried out quantum-mechanical studies of the organometallic allenes envisioned by the isolobal replacement of the terminal CH2 groups by the d8 Fe(CO)4 fragment. Our studies have identified two organometallic allenes viz. D2d symmetric [(μ-C)(Fe(CO)4 )2 ] (2) and D3 symmetric [(μ-C)(Fe(CO)4 )2 ] (3) with trigonal bipyramidal coordination at the Fe atoms. Compound 2 features the bridging carbon atom in an equatorial position with respect to the ligands on the TM centre, while 3 features the central carbon atom in an axial position. The bis-pseudoallylic anionic delocalisation proposed in the C2-C1-C3 spine of organic allene is retained in the organometallic allene 2, and is transformed to a typical three-centre bis-allylic anionic delocalisation in the organometallic allene 3. The topological analysis of electron density also indicates a bis-allylic anionic type delocalisation in the organometallic allenes. The quantitative bonding analysis using the EDA-NOCV method suggests a transition from classical electron-sharing bonding between the central carbon atom and the terminal groups in 1 to donor-acceptor bonding in 3. Meanwhile, both electron-sharing and donor-acceptor bonding models are found to be probable heuristic bonding representations in the organometallic allene 2.

New Complexes of Antimony(III) with Tridentate O,E,O-Ligands (E = O, S, Se, Te, NH, NMe) Derived from N-Methyldiethanolamine.

We synthesized a series of new antimony(III) compounds by reaction of Sb(OEt)3 with organic ligands of the type E(CH2-CH2-OH)2, with E = NH, NMe, O, S, Se, and Te. The synthesized compounds have the general composition [E(CH2-CH2-O)2]Sb(OEt). For comparison, the compound (O-CH2-CH2-S)Sb(OEt) was prepared. All compounds are characterized using NMR, IR, and Raman spectroscopy. The molecular structures of the products reveal the formation of chelate complexes, wherein the ligand molecules coordinate as tridentate O,E,O-ligands to the antimony atom. Dimer formation in the solid state allows the antimony atoms to reach pentacoordination. Quantum chemical calculations including topological analysis of electron density reveal that there are polar shared bonds between antimony and the oxygen atoms bound to antimony. The interactions between the donor atom E and the Sb atom and the interactions in the dimers can be characterized as Van der Waals interactions. The reactivity of [MeN(CH2-CH2-O)2]Sb(OEt) was investigated as an example. For this purpose, the compound reacted with a range of organic compounds such as carboxylic acids and carboxylic anhydrides and small molecules like CO2 and NH3. This study establishes a new and easy accessible class of antimony(III) compounds, provides new insights into the chemistry of antimony compounds and opens up new opportunities for further research in this field.

Comparison of experimental and theoretical spectral groups, electronic properties, topological, and molecular docking investigations of 1-N-Cbz-piperidine-4-carboxylic acid- Potential Cancer drug

In this present work, the theoretical and experimental spectroscopic (FT-IR, FT-Raman) investigations were performed for 1-N-Cbz-piperidine-4-carboxylic acid (1NCPA). The theoretical approaches were computed using Density Functional Theory (DFT)/ B3LYP/6–311++G(d,p) as a basis set. Using the aforementioned basis set, the optimized molecular geometrical parameters and computed wavenumbers were determined. The theoretical (TD-SCF) UV–Vis's spectra for the solvent phases and recorded wavelength were compared to one another. Frontier molecular orbitals (energy parameters), hole-electron distribution for the excited states, and ESP analyses were reported. The QTAIM theory was used to accomplish the topological analysis of electron density. Further, ELF, LOL, and RDG analyses were reported. The title compound (as a ligand) and ALK inhibitors (as protein) with their bonding interactions were studied using molecular docking analysis. It was compared with the standard drug and the least binding energy was calculated.

Effect of Halogen at the Divalent Sulfur Atom on the Properties of Complexes with a Chalcogen and Hydrogen Bond

Binary complexes with a chalcogen (A complexes) and hydrogen (B complexes) bond formed by SHX molecules (X = F, Cl, Br, OH) of divalent sulfur and a water molecule have been calculated by the MP2/aug-cc-pVTZ quantum chemical method. An NBO analysis was performed for complexes of both types along with the topological analysis of electron density and decomposition of the binding energy into components. The quantum chemical calculations showed that the binding energies, interorbital interaction energies of monomers, and electron densities at the critical point (3, –1) of intermolecular contact are close in the A and B complexes. The main contribution to stabilization of the complexes is made by the electrostatic interaction; in the B complexes, however, the contribution of the charge transfer component is also significant. The dispersion energy plays a significant role in the binding of monomers in complexes of both types. According to the calculations, the interconversion of A and B complexes occurs with a very low activation barrier.

Structural and theoretical study of π-stacking interactions in new complexes based on CuCl2 and 3-sulfonamide-substituted imidazo[2,1-b]thiazoles.

At present, sulfonamides and their metal complexes have received a new impetus for development. Of particular interest is the study of molecular and crystal structures, which takes into account weak non-valent interactions. Despite the low energy of such interactions, in many cases, they act collectively, and the sum of their actions can play a significant role. As a result, the spectrum of medical and biological activity of new metal complexes is expanded. In this regard, the synthesis and study of the molecular and crystal structure of sulfonamides and their metal complexes is of undoubted relevance. In this work, we studied non-valent intra- and intermolecular interactions in ligands of sulfonamide-substituted imidazo[2,1-b]thiazoles and their previously unknown complexes with CuCl2. The performed analysis of the data obtained by X-ray diffraction analysis made it possible to establish the intramolecular π-stacking interaction in imidazothiazole ligands, which is retained in their complexes with CuCl2. Within the framework of QTAIM topological analysis of electron density and DORI analysis, stereoelectronic and topological structures were studied. In the complexes, tetral, chalcogen, and pnycogen new interligand non-valent interactions were established. The energies of all established types of non-valent interactions have been calculated, and their comparative evaluation has been made. X-ray data of new arylsulfonylamino-substituted derivatives of imidazo[2,1-b]thiazoles and their metal complexes with CuCl2 have been studied. To determine the theoretical prerequisites for the occurrence of π-stacking in the molecules under study, the QTAIM method was used in the framework of the DFT/B3LYP/6-311 + G(d) calculation using the GAUSSIAN 09 program. In addition, the DORI electron density region overlap indicator and the Multiwfn program were used to analyze non-valent interactions.

On the Nature of the Partial Covalent Bond between Noble Gas Elements and Noble Metal Atoms

This article provides a discussion on the nature of bonding between noble gases (Ng) and noble metals (M) from a quantum chemical perspective by investigating compounds such as NgMY (Y=CN, O, NO3, SO4, CO3), [NgM-(bipy)]+, NgMCCH, and MCCNgH complexes, where M=Cu, Ag, Au and Ng=Kr-Rn, with some complexes containing the lighter noble gas atoms as well. Despite having very low chemical reactivity, noble gases have been observed to form weak bonds with noble metals such as copper, gold, and silver. In this study, we explore the factors that contribute to this unusual bonding behavior, including the electronic structure of the atoms involved and the geometric configuration of the concerned fragments. We also investigate the metastable nature of the resulting complexes by studying the energetics of their possible dissociation and internal isomerization channels. The noble gas-binding ability of the bare metal cyanides are higher than most of their bromide counterparts, with CuCN and AgCN showing higher affinity than their chloride analogues as well. In contrast, the oxides seem to have lower binding power than their corresponding halides. In the oxide and the bipyridyl complexes, the Ng-binding ability follows the order Au > Cu > Ag. The dissociation energies calculated, considering the zero-point energy correction for possible dissociation channels, increase as we move down the noble gas group. The bond between the noble gases and the noble metals in the complexes are found to have comparable weightage of orbital and electrostatic interactions, suggestive of a partial covalent nature. The same is validated from the topological analysis of electron density.

Charge-Shifted Weak Noncovalent Interactions in the Atmospherically Important OCS Microhydrates.

Stratospheric aerosol, mainly comprising microhydrated carbonyl sulfide (OCS), is among the primary drivers of climate change. In this study, we investigate the effect of microhydration on the structure, energetics, and vibrational properties of the neutral OCS molecule using ab initio calculation, molecular electrostatic potential (MESP), topological analyses of electron density, and natural bond orbital (NBO) analyses. The complexation energy increases with the cluster size, and the first solvation shell of OCS consists of four water molecules that interact with the OCS moiety preferentially through SOCS···OW, OOCS···OW, and COCS···OW type of weak noncovalent interaction instead of the typical OOCS···H-OW and SOCS···H-OW H-bonds. These noncovalent interactions originate due to the electron shift from the water oxygen lone pair to the antibonding orbital of C═S [BD*(C═S)], sometimes via BD*(C═O), which substantially perturbs the bending mode of surrounding water molecules. The present study thus unravels the underlying relationship between the OCS atmospheric hydrolysis and the charge-shifted noncovalent interactions.

Mechanism study on H2S capture of ionic liquids based on triethylenetetramine blended with ethylene glycol

Amino-functionalized ILs are promising absorbents for H2S. In this work, three triethylenetetramine functionalized ionic liquids (TETAH-ILs) were synthesized and applied to construct mixture solutions with ethylene glycol (EG). Among [TETAH][HCOO]-EG, [TETAH][BF4]-EG and [TETAH]Br-EG absorbents, [TETAH][BF4]-EG showed the greatest H2S absorption capacity. In addition, a series of factors, such as IL molar fraction, absorption temperature and H2S flow rate, were also investigated to evaluate the effects on absorption performance of [TETAH][BF4]-EG absorbent. The results showed that the 10 % [TETAH][BF4]-EG mixed solution has excellent absorption capacity (1.128 mol H2S/mol IL) at 303.15 K and 100 mL/min. In addition, the absorbent could remain 75.12 % absorption capacity after four regenerations, which displayed potential for reversibility. Furthermore, the mechanism of H2S absorption by TETAH-ILs was proposed by combining FT-IR and 1H NMR characterization and electron density topology analysis. Furthermore, the mechanism of H2S absorption by TETAH-ILs was proposed by combining FT-IR and 1H NMR characterization and theoretical calculation. The results revealed that the mechanism of H2S absorption by TETAH-ILs was the formation of IL-H2S complexes through a series of hydrogen bonds.