Energy Decomposition Analysis Research Articles

From Biological Activity to Stereoselectivity: A Portrait of Molecular and Mechanistic Profiles of the Therapeutic Potential of G-1 and LNS8801 as GPER-1 Activator in the Treatment of Waldenström’s Macroglobulinemia

Therapeutic activation of G protein-coupled estrogen receptor 1 (GPER-1) shows promise for treating Waldenström's Macroglobulinemia (WM). Recently, the selective small-molecule agonist G-1 or its enantiomer LNS8801 were reported as potent GPER-1 pharmacological activators, however, the molecular events surrounding their chirality towards GPER-1 is still unexplored. This study aimed to explore the molecular events surrounding the chirality of the selective small-molecule agonists G-1 and LNS8801 towards GPER-1. Molecular docking and dynamics simulations revealed strong binding affinities and key amino acid residues involved in the activation process. The results revealed favourable binding affinities of -29.87kcal/mol, and -28.09kcal/mol for G-1 and LNS8801 towards GPER-1, respectively. Per-residue energy decomposition and time-dependent analysis proved that Arg253 and Arg254 are key amino acid residues in binding these activators towards GPER-1. The activators affected stability, flexibility, and structure of GPER-1. G-1 exhibited greater rigidity when bound to GPER-1 compared to LNS880. This study's findings illuminate chirality and the potential for optimizing the enantiomer ratio to enhance inhibitory effects. These results could also reveal the molecular specifics and binding mechanism of the G-1 and its enantiomer LNS8801 with GPER-1, laying the basis for the rational design of enhanced chiral molecules against WM.

Reactivities and Bohmian perspectives on pnictogen N-heterocyclic carbene analogues reactions with methane and ethene

The chemical reactions of monocationic pnictogen N-heterocyclic carbene (NHC) analogues [(tBu2DAB)M+, M = N, P, As, Sb, and Bi, and tBu2DAB =1,4-tert-butyl-1,4-diaza-1,3-butadiene] with methane and ethene are studied by the density functional theory. The activation energies and reaction enthalpies are analyzed by the natural energy decomposition analysis (NEDA) to understand the reactivities of the reactions. The activation energies and reaction enthalpies of the ethene reactions, and the activation energies of the methane reactions decrease with the atomic numbers of the pnictogen elements M. However, the reaction enthalpies of the methane reactions do not follow a monotonic trend because the size and geometry of the methane structure are better accommodated by the product states of (tBu2DAB)P+ than (tBu2DAB)N+. The NEDA also suggests that the carbene and hydrocarbon fragments are subject to singlet–singlet interactions for all reactions of this work. The electronic and energetic structures of the reactions involving the N-centered NHC reactant, (tBu2DAB)N+ characteristically differ from all other carbenic reactants, which is in agreement with the well-known fact that the 2s and 2p orbitals of the N atom are more amenable to hybridization than the higher s and p orbitals of other pnictogen elements. The Bohmian perspectives on the stationary states of the pnictogen NHC reactions are also explored. It is found that the Bohmian potentials may reveal some bonding informations of the complexes, but further investigations are still required for deeper understanding.

The formation of nickelalactone in CO2/C2H4 coupling reaction: A benchmark, dispersion correction, and energy decomposition analysis

The oxidative coupling of CO2 and ethylene for synthesizing acrylic acid and its derivatives is considered one of the “dream reactions” in catalysis. The formation of acrylic acid by CO2/C2H4 coupling is hardly possible due to the endothermic nature of the reaction. This work reports a comprehensive study of the nickelalactone formation from CO2/C2H4 coupling over Ni-catalysts. We have evaluated the accuracy of the DLPNO-CCSD(T) method in determining the barrier heights and the reaction energetics for the nickelalactone formation. Extrapolation to the complete basis set limit was performed using two-point extrapolation methods. It was found that the DLPNO-CCSD(T) method, in combination with the complete basis set cc-pVTZ/cc-pVQZ extrapolation, gives the error within 1.0 kcal/mol. To gain a molecular understanding of the formation of acrylic acid by CO2/C2H4 coupling, the distortion-interaction model was used as an energy decomposition method to analyze the inner- and outer-sphere reaction transition states, considering two competing pathways. It was found that i) the inner-sphere reaction is superior to the outer-sphere reaction owing to the lower distortion energy and stronger interactions, ii) three prominent pairs of orbital interactions exist between the Ni-C2H4 complex and the CO2 molecule, and iii) the dispersion correction is crucial to obtaining reliable non-covalent interaction energies.

β-D-Glucopyranose-silver+ (1:1) complex as a small gas molecule scavenger.

In this article, density functional theory computations at the PBE0-D3/def2-TZVP level are reported to unveil the type of bonding between β-D-glucopyranose-silver ion (1:1) complex ([Ag(C6H12O6)]+) and seven gas molecules, namely, H2, C2H2, C2H4, CO, N2, NO and O2. Moreover, the relative preference of trapping among these molecules within the sight of Ag metal ion in the complex is explored. The nature of interaction of these small molecules with the [Ag(C6H12O6)]+ ion is studied. Exergonic nature of binding is noted with the metal center for all the chosen small molecules except O2. Thermochemical data reveals the binding preference of C2H4 > C2H2 > CO > NO > N2 > H2. Natural bond orbital analysis, contour plot of the Laplacian of electron density, electron density descriptors, and gradient isosurface help in understanding the nature of interactions. Maximum bond formation is noted between the Ag-complex and CO molecule. Assessed energy decomposition analysis discloses the nature of interaction as mainly orbital between the bound small gas molecules and the Ag-complex. Frontier molecular orbital pictures further help in understanding the type of interaction as orbital. To disclose the kinetic stability of the gas molecule bound Ag complexes an ab initio molecular dynamics study is done at different temperatures up to 2 ps. These studies help in understanding the type of adsorption. Calculated conceptual density functional theory (CDFT) based reactivity descriptors corroborate well with results. β-D-glucopyranose-silver ion (1:1) complex may be used as small gas molecule scavenger.

Understanding Alkene Interaction with Metal-Modified Zeolites: Thermodynamics and Mechanism of Bonding in the π-Complex.

Zeolites modified with metal cations are perspective catalysts for converting light alkenes to valuable chemicals. A crucial step of the transformation is an alkene interaction with zeolite to afford π-complex with metal cations. The mechanism of alkene bonding with cations is still unclear. To address this problem, propene adsorption on H+ (Bro̷nsted acid site), Na+, Ca2+, Zn2+, Co2+, Cu2+, Cu+, and Ag+ cationic sites in ZSM-5 zeolite has been studied by quantum chemical calculations in terms of adsorption enthalpy, νC═C frequency, and natural bond orbital (NBO) analysis together with natural energy decomposition analysis (NEDA). It is revealed that the conventional concept of σ- and π-bonding is only partially applicable to alkene interaction with metal cations in zeolites. The orbital interaction between an alkene molecule and a metal site is more complex. Several different bonding mechanisms have been identified depending on the nature and electron configuration of the metal cation. This finding explains the complex correlations observed for propene π-complex stability and νC═C frequency shift or charge transfer from the alkene molecule. The results provide the basis for further understanding the interactions between alkenes and inorganic solid Bro̷nsted and Lewis acids.

Synthesis, Molecular Docking, Anti-cholinesterase Activity, Theoretical Investigation, and Catalytic Effect of New Encumbered N-benzyladamantyl Substituted Imidazolidin-2-ylidene Carbene Pd-PEPPSI Complexes

Abstract: This study aimed to describe the preparation of novel PEPPSI type Pd(II)-NHC complexes bearing N-benzyladamantyl substituted imidazolidin-2-ylidene group. All synthesized compounds were characterized by using 1H-NMR and 13C-NMR spectroscopies, FTIR, and elemental analysis techniques. One of the objectives of this study was the synthesis of Pd-NHC complexes with AChE/BChE inhibition activities. Among all the tested compounds, complexes 4b and 4c were found to have the most high potential AChE and BChE inhibitory activities with IC50 values of 21.57 ± 0.23 Mm and 15.78 ± 0.39 Mm, respectively. Conducting molecular docking studies helped us in gathering crucial information about the main binding interactions of inhibitors and enzymes, and the results were in agreement with the biological evaluation. The synthesized Pd-NHC complexes were employed for catalyzing the direct C2- and C5-arylation reaction between aryl (hetero) halide and a variety of heterocyclic systems. In both cases (C2 and C5-arylation), Pd-NHC complexes catalysts provided access to the arylated heterocycles in good to high yields in the presence of 1 mol% catalyst loading at 150°C. The DFT theoretical investigation showed that the Pd-NHC complexes were of ML2X2 type, where the the Pd(II) cation had a square planar geometry. The interaction energies obtained by energy decomposition analysis (EDA) demonstrated that the 4d and 4e complexes were more stable in the presence of more methyl substituents. The chemical indicators demonstrated that the less stable 4c complex was more reactive in regard to the chemical hardness, chemical potential, and electrophilicity values.

Exploring the bonding and aromaticity of [Au3{C2H2N2E(L)2}3]+ (E = Si, Ge and L = –CH3, -H, -CF3, –NO2): Trinuclear gold superalkali complexes

Coinage metal [Cu, Ag, Au] complexes, with carbene analogous ligands, especially silylene, and germylene, have been getting attention in recent years for their potential applications, either in homogeneous catalysis or in photophysical properties. In this study, we have designed trinuclear gold complexes with different substituted silylene and germylene and observed that these trinuclear gold complexes are stable in cationic form and behave like a superalkali. Conceptual density functional theory (CDFT) based descriptors like electrophilicity give the idea about the reactivity of these superalkali complexes. Negative NICS values determine the aromatic nature of the trinuclear core of these complexes. Atom in molecules (AIM) study has been performed to gain a clear idea about the bonding nature of complexes. Energy decomposition analysis (EDA) suggests that electrostatic interaction stabilizes the complex. First-order hyperpolarizability calculation confirms their high nonlinear optical (NLO) properties.

Conformational Preference of Lithium Polysulfide Clusters Li2Sx (x = 4-8) in Lithium-Sulfur Batteries.

Structures are of fundamental importance for diverse studies of lithium polysulfide clusters, which govern the performance of lithium-sulfur batteries. The ring-like geometries were regarded as the most stable structures, but their physical origin remains elusive. In this work, we systematically explored the minimal structures of Li2Sx (x = 4-8) clusters to uncover the driving force for their conformational preferences. All low-lying isomers were generated by performing global searches using the ABCluster program, and the ionic nature of the Li···S interactions was evidenced with the energy decomposition analysis based on the block-localized wave function (BLW-ED) approach and further confirmed with the quantum theory of atoms in molecule (QTAIM). By analysis of the contributions of various energy components to the relative stability with the references of the lowest-lying isomers, the controlling factor for isomer preferences was found to be the polarization interaction. Notably, although the electrostatic interaction dominates the binding energies, it contributes favorably to the relative stabilities of most isomers. The Li+···Li+ distance is identified as the key geometrical parameter that correlates with the strength of the polarization of the Sx2- fragment imposed by the Li+ cations. Further BLW-ED analyses reveal that the cooperativity of the Li+ cations primarily determines the relative strength of the polarization.

Directionality of Halogen-Bonds: Insights from 2D Energy Decomposition Analysis.

Halogen bonds are typically observed to have a linear arrangement with a 180° angle between the nucleophile and the halogen bond acceptor X-R. This linearity is commonly explained using the σ-hole model, although there have been alternative explanations involving exchange repulsion forces. We employ two-dimensional Distortion/Interaction and Energy Decomposition Analysis to examine the archetypal H3 N⋯X2 halogen bond systems. Our results indicate that although halogen bonds are predominantly electrostatic, their directionality is largely due to decreased Pauli repulsion in linear configurations as opposed to angled ones in the I2 and Br2 systems. As we move to the smaller halogens, Cl2 and F2 , the influence of Pauli repulsion diminishes, and the energy surface is shaped by orbital interactions and electrostatic forces. These results support the role of exchange repulsion forces in influencing the directionality of strong halogen bonds. Additionally, we demonstrate that the 2D Energy Decomposition Analysis is a useful tool for enhancing our understanding of the nature of potential energy surfaces in noncovalent interactions.

Matrix-isolation FTIR spectroscopic study and quantum chemical calculations of 1:1 adduct of CHCl3 and C2H5OH in N2 matrix

[▪-▪] mixture is a common binary solvent used in industries, organic synthesis, lipid extraction, drug extraction, etc. The purpose of this study is to have a molecular level understanding of the interaction of ▪ with ▪. The experiments have been carried out in low temperature ▪ matrix using Fourier Transform Infrared spectroscopy. Electronic structure calculations have been performed to identify the possible binding motifs between ▪ and ▪. Three minima have been obtained on the dimer potential energy surface stabilised by ▪ and ▪ hydrogen bond, and ▪ halogen bond interactions. Formation of more than one complexes have been confirmed using the experimental and simulated IR spectra. Energy decomposition analysis and Natural bond orbital analysis have been performed to understand the nature of interaction and the driving force for complexation. This is one of the first reports where separate complexes have been identified between ▪ and anti and gauche conformers of ▪ in the low temperature matrix.

Catalyst-Controlled Intermolecular Homobenzylic C(sp3)-H Amination for the Synthesis of β-Arylethylamines.

The combination of a tailored sulfamate with a C4-symmetrical rhodium(II) tetracarboxylate allows to uncover a selective intermolecular amination of unactivated homobenzylic C(sp3)-H bonds. The reaction has a broad scope (>30 examples) and proceeds with a high level of regioselectivity with homobenzylic/benzylic ratio of up to 35:1, thereby providing a direct access to β-arylethylamines that are of utmost interest in medicinal chemistry. Computational investigations evidenced a concerted mechanism, involving an asynchronous transition state. Based on a combined activation strain model and energy decomposition analysis, the regioselectivity of the reaction was found to rely mainly on the degree of orbital interaction between the [Rh2]-nitrene and the C-H bond. The latter is facilitated at the homobenzylic position due to the establishment of specific noncovalent interactions within the catalytic pocket.

In Silico Analysis of the Aromaticity of Some Carbo-Metallabenzenes and Carbo-Dimetallabenzenes (Carbo-mers Proposed from Metallabenzenes).

In the current work, we introduce a novel class of molecules termed carbo-metallabenzenes, and their aromaticity has been comprehensively analyzed. The molecules were strategically designed with the insertion of acetylene (C≡C or C2) units in some selected metallabenzenes. Furthermore, if a second metallic unit is inserted (replacing a sp2 carbon) in the carbo-metallabenzenes rings, a new family of carbo-mers is generated, and this second group has been named as carbo-dimetallabenzenes. The primary objective of this work is to ascertain, through various methodologies, whether these newly proposed molecules retain the aromatic characteristics observed in carbo-benzene. The methodologies employed for bond analysis and aromaticity exploration include the analysis of the molecular orbitals, energy decomposition analysis, electron density of delocalized bonds, magnetically induced current density, and the induced magnetic field (Bind). This study sheds light on that the insertion of the metallic centers reduces the electronic delocalization and their aromaticity is, in some cases, comparable with the electronic delocalization of the inorganic iminobora-borazine and also provides valuable insights into their electronic structure through a multifaceted analysis.

Size Matters: Computational Insights into the Crowning of Noble Gas Trioxides.

In pursuit of enhancing the stability of the highly explosive and shock-sensitive compound XeO3, we performed quantum chemical calculations to investigate its possible complexation with electron-rich crown ethers, including 9-crown-3, 12-crown-4, 15-crown-5, 18-crown-6, and 21-crown-7, as well as their thio analogues. Furthermore, we expanded our study to other noble gas trioxides (NgO3), namely, KrO3 and ArO3. The basis set superposition error (BSSE) corrected interaction energies for these adducts range from -13.0 kcal/mol to -48.2 kcal/mol, which is notably high for σ-hole-mediated noncovalent interactions. The formation of these adducts was observed to be more favorable with the increase in the ring size of the crowns and less favorable while going from XeO3 to ArO3. A comprehensive analysis by various computational tools such as the mapping of the electrostatic potential (ESP), Wiberg bond indices (WBIs), Bader's theory of atoms-in-molecules (AIM), natural bond orbital (NBO) analysis, noncovalent interaction (NCI) plots, and energy decomposition analysis (EDA) revealed that the C-H···O interactions, as well as dispersion interactions, play a pivotal role in stabilizing adducts involving larger crowns. A noteworthy outcome of our study is the revelation of a coordination number of 9 for xenon in the complex formed between XeO3 and the thio analogue of 18-crown-6, which is higher than the largest number reported to date.

Enhancement of gas adsorption on transition metal ion-modified graphene using DFT calculations.

Graphene-based nanomaterial was widely used in gas sensors, detection, and separation. However, weak adsorption and low selectivity of the pristine graphene used for gas sensors are major problems. Here, using density functional theory (DFT) calculations, we reported the significant increase of four gas molecules (N2, CO2, C2H2, and C2H4) adsorption on the transition metal ion (Fe3+, Co2+, Ni2+)-modified graphene complex (Fe3+/Co2+/Ni2+-G) comparing to be absorbed on the pristine graphene (G). Moreover, the Co2+-G is suitable for the selective separation of C2H4/C2H2 due to the larger adsorption energy difference (8.5kcal/mol) between them. The addition of transition metal ions also decreased the HOMO-LUMO gap of the systems, which benefits the enhancement of electrical conductivity. This suggests that the transition metal ion-modified graphene can be used to distinguish the different gas molecule's adsorption, facilitating the design of graphene-based gas sensors and selective separation. All the density functional theory (DFT) calculations were performed by B3LYP with the GD3 dispersion method using Gaussian 16 software. The basis set 6-31G(d) was used for C, H, O, and N atoms, and Lanl2DZ was used for transition metal ions (Fe3+, Co2+, Ni2+). The DOS analysis and energy decomposition analysis were performed using the Multiwfn program.

Exploring Unconventional σ-Hole Interactions: Computational Insights into the Interaction of XeO3 with Non-Aromatic Coordinating Solvents.

In order to control the explosiveness and shock sensitivity of XeO3 , we have investigated its plausible interaction with various non-aromatic coordinating solvents, serving as potential Lewis base donors, through density functional theory (DFT) calculations. Out of twenty six such solvents, the top ten were thus identified and then thoroughly examined by employing various computational tools such as the mapping of the electrostatic potential surface (MESP), Wiberg bond indices (WBIs), non-covalent interaction (NCI) plots, Bader's theory of atoms-in-molecules (AIM), natural bond orbital (NBO) analysis, and the energy decomposition analysis (EDA). The amphoteric nature of XeO3 was also explored by investigating the extent of back donation from the lone pair of Xe to the antibonding orbital of the donating atom/group of the solvent molecules. The C-H…O interactions were also found to be a contributing factor in the stabilization of these adducts. Although these aerogen-bonding interactions were found to be predominantly electrostatic, significant contributions from the orbital contributions, as well as dispersion interactions, were observed. The top three non-aromatic solvents (among the twenty six studied) which form the strongest adducts with XeO3 are proposed to be hexamethylphosphoramide (HMPA), N,N'-dimethylpropyleneurea (DMPU) and tetramethylethylenediamine (TMEDA).

A Deeper Insight into the Supramolecular Activation of Oxidative Addition Reactions Involving Pincer-Rhodium(I) Complexes.

The factors governing the acceleration of the oxidative addition of methyl iodide to pincer rhodium(I)-complexes induced by coronene have been computationally explored in detail using quantum chemical methods. Both the parent reaction and the coronene-mediated process proceed via a stepwise SN2-type mechanism. It is found that the acceleration of the process derives from the formation of an initial supramolecular complex, mainly stabilized by electrostatic and π-π interactions, which significantly increases the electron richness of the complex. The impact of this effect on the reaction barrier has been quantitatively analyzed by applying the activation strain model in combination with the energy decomposition analysis method. In addition, the influence of other polycyclic aromatic hydrocarbons on the oxidative reaction has been also considered.

Observation of a super-tetrahedral cluster of acetonitrile-solvated dodecaborate dianion via dihydrogen bonding

We launched a combined negative ion photoelectron spectroscopy and multiscale theoretical investigation on the geometric and electronic structures of a series of acetonitrile-solvated dodecaborate clusters, i.e., B12H122−·nCH3CN (n = 1–4). The electron binding energies of B12H122−·nCH3CN are observed to increase with cluster size, suggesting their enhanced electronic stability. B3LYP-D3(BJ)/ma-def2-TZVP geometry optimizations indicate each acetonitrile molecule binds to B12H122− via a threefold dihydrogen bond (DHB) B3–H3 ⁝⁝⁝ H3C–CN unit, in which three adjacent nucleophilic H atoms in B12H122− interact with the three methyl hydrogens of acetonitrile. The structural evolution from n = 1 to 4 can be rationalized by the surface charge redistributions through the restrained electrostatic potential analysis. Notably, a super-tetrahedral cluster of B12H122− solvated by four acetonitrile molecules with 12 DHBs is observed. The post-Hartree–Fock domain-based local pair natural orbital- coupled cluster singles, doubles, and perturbative triples [DLPNO-CCSD(T)] calculated vertical detachment energies agree well with the experimental measurements, confirming the identified isomers as the most stable ones. Furthermore, the nature and strength of the intermolecular interactions between B12H122− and CH3CN are revealed by the quantum theory of atoms-in-molecules and the energy decomposition analysis. Ab initio molecular dynamics simulations are conducted at various temperatures to reveal the great kinetic and thermodynamic stabilities of the selected B12H122−·CH3CN cluster. The binding motif in B12H122−·CH3CN is largely retained for the whole halogenated series B12X122−·CH3CN (X = F–I). This study provides a molecular-level understanding of structural evolution for acetonitrile-solvated dodecaborate clusters and a fresh view by examining acetonitrile as a real hydrogen bond (HB) donor to form strong HB interactions.

Introduction of 5-membered boron-oxygen-heterocyclic carbene and its Si and Ge homologs and the M–L bonding analysis in their complexes with coinage metals: A theoretical study

Replacing an oxygen atom with one of the boron atoms in a 5-membered B-Heterocyclic carbene and its Si and Ge congeners (BHEs; E = C, Si, Ge) creates Boron-Oxygen-Heterocyclic divalents (BOHEs) which may have potential uses as organometallic ligands. In addition to a survey on their singlet–triplet energy gap (ΔET-S) for the stability concerns, the nature of the E–M bonds in XBOHE–MCl complexes (M = CuI, AgI, AuI; E = C, Si, Ge; X = F, Cl, Br) is theoretically investigated using the natural bond orbital (NBO), energy decomposition analysis (EDA), and extended transition state natural orbital for chemical valence (ETS-NOCV) analysis. The outcomes show interesting stabilities of singlet/triplet configurations in carbenes, silylenes, and germylenes. Also, the results exhibit that the E–M bonds in the complexes have a higher electrostatic character.

Computational study on the characteristics of the complexes resulting from the interaction of carbonyl selenide and hypohalous acids

This study computationally investigates the properties and competition of complexes formed by the interaction between hypohalous acids (HOX, where X = F, Cl, Br, and I) and carbonyl selenide (COSe) at the MP2/aug-cc-pVTZ computational level. Three distinct groups of complexes were obtained. The first group, consisting of complexes with a cyclic structure (HB-TB), exhibited the highest stability. remaining two groups formed less stable linear structures with different characteristics (ChB and XB). In the first group, the electronegativity of the halogen atom significantly influenced the stability of the complexes. Conversely, the stability of complexes in groups II and III was primarily determined by the acid and base strengths of the interacting monomers. To comprehensively evaluate the obtained results, various analyses were employed, including Molecular electrostatic potential (MEP), geometry Optimization, Spectroscopic, Interaction energy (SE), Natural bond orbital (NBO) analysis, Atoms in molecules (AIM) analysis, Non-covalent interaction (NCI) index, Energy decomposition analysis (EDA), and Electron density difference(EDD) analysis.

3-styrylcoumarin scaffold-based derivatives as a new approach for leishmaniasis intervention: biological and molecular modeling studies

Seven 3-styrylcoumarins were tested for antileishmanial activity against Leishmania (Viannia) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. The 3-methoxy-4-hydroxy coumarin derivative 6 was the most active with an IC50 of 40.5 µM, and did not reveal any conspicuous toxicity toward mammalian U-937 cells. Therefore, it may have potential to be considered as candidate for antileishmanial drug development. Further, among several druggable Leishmania targets, molecular docking studies revealed that compound 6 had docking preference by the N-myristoyltransferase (Lp-NMT) of Leishmania panamensis, showing a higher docking score of − 10.1 kcal mol−1 than positive controls and making this protein as a presumably druggable target for this compound. On the other hand, molecular dynamics simulations affirm the docking hypothesis, showing a conformational stability of the 6/Lp-NMT complex throughout 100 ns simulation. Moreover, the molecular mechanics/Poisson–Boltzmann surface area method also support the docking findings, revealing a total free energy of binding of − 47.26 ± 0.08 kcal mol−1, and identifying through energy decomposition analysis that those key aminoacids are contributing strongly to ligand binding. Finally, an optimal pharmacokinetic profile was also estimated for 6. Altogether, coumarin 6 could be addressed as starting point for further pharmacological studies concerning the therapeutic leishmaniasis intervention.Graphical abstract