QTAIM Approach Research Articles

Organic Moiety on Sn(IV) Does Matter for In Vitro Mode of Action: nBu3Sn(IV) Compounds with Carboxylato N-Functionalized 2-Quinolones Induce Anoikis-like Cell Death in A375 Cells

Objectives: New tributyltin(IV) complexes containing the carboxylate ligands 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoic acid (HL1) and 2-(4-methyl-2-oxoquinolin-1(2H)-yl)acetic acid (HL2) have been synthesized. Methods: Their structures have been determined by elemental microanalysis, FT-IR and multinuclear NMR (1H, 13C and 119Sn) spectroscopy and X-ray diffraction study. A solution state NMR analysis reveals a four-coordinated tributyltin(IV) complex in non-polar solvents, while an X-Ray crystallographic analysis confirms a five-coordinated trigonal-bipyramidal geometry around the tin atom due to the formation of 1D chains. A theoretical structural analysis was performed by optimization employing B3LYP-D3BJ functional and 6-311++G(d,p)/def2-TZVP(Sn) basis sets for H, C, N, O/Sn, respectively. The interactions between tin(IV) and surrounding atoms were examined by QTAIM approach. The in vitro antiproliferative activity of the synthesized compounds was evaluated by MTT and CV assays versus MCF-7 (human breast adenocarcinoma), HCT116 (human colorectal carcinoma), A375 (human melanoma), 4T1 (mouse breast carcinoma), CT26 (mouse colon carcinoma) and B16 (mouse melanoma) tumor cell lines. Results: Both synthesized compounds (nBu3SnL1 and nBu3SnL2) exerted powerful micromolar IC50 cytotoxicity values and demonstrated high selectivity toward malignant cells. Both experimental drugs affected cell adhesion and induced anchorage independent apoptosis, a favorable type of cell death with an essential role in cancer dissemination prevention. The BSA-binding affinity of the obtained organotin compounds was followed by spectrofluorometric titration and molecular docking simulations. Conclusions: The tributyltin(IV) compounds selectively induce anoikis-like cell death in A375 cells, also highlighting the importance of the organic moiety on the tin(IV) ion in the mechanism of action.

Characterization of 1,1- and 1,2-ethenedithiol, elusive compounds of potential astrochemical interest.

1,1- and 1,2-ethenedithiol are elusive systems that could potentially exist in interstellar space, similar to analogous diols. In this paper, we investigate the structure, stability, and bonding characteristics of these compounds as well as the ions produced by protonation, deprotonation, or simple ionization processes. 1,2-ethenedithiol has two isomers, Z and E, with the most stable conformer being syn-anti for the Z isomer and anti-anti for the E isomer. However, the energy gaps between the different conformers are never larger than 6kJ·mol-1. For 1,1-ethenedithiol, the global minimum is the syn-anti conformer. The vertical and adiabatic ionization processes as well as the intrinsic basicities and acidities of these families of compounds were analyzed and compared with those of the corresponding diols previously reported in the literature. This comparison revealed not only the numerical differences in these thermodynamic properties but also distinct trends between the two families of compounds. State-of-the-art G4 ab initio calculations were employed to calculate the structures and total energies of the systems under investigation. The QTAIM, ELF, and NBO approaches were used to analyze the electron density of all the neutral and charged systems included in our study. Van der Waals contributions, when relevant, were analyzed by locating regions of low reduced density gradient(s) using the NCIPLOT approach.

Evaluation of charge-assisted hydrogen bonds and weak intermolecular interaction in trimethoprim 2-aminobenzoate: A combined crystallographic and theoretical approach

A comprehensive investigation of the weak non-covalent interactions within the crystal structure of trimethoprim 2-aminobenzoate (2,6-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidin-1-ium 2-aminobenzoate) is presented. The protonation of trimethoprim and the deprotonation of 2-aminobenzoate were confirmed by NMR spectroscopy and a single-crystal X-ray diffraction study. Qualitative Hirshfeld surface analysis identified intermolecular H···H, O···H, and C···H contacts as the three primary interactions within the title salt. Fourteen molecular pairs (M1AA−M14AB) were extracted from the crystal packing of the title salt using the PIXEL method. These molecular dimers were further characterized using the QTAIM and DFT approaches. Seven intermolecular pairs (M1AA−M7BB) formed between like-charged species (i.e. +1···+1 or -1···-1) resulted in destabilization, with total energies (Etot) ranging from 67.2 to 200.1 kJ mol-1. Conversely, molecular pairs formed between oppositely charged species (i.e. +1···-1) exhibited stabilizing behavior, with interaction energies ranging from -133.7 to -449.7 kJ mol-1. Topological analysis of charge density revealed that two N–H···O hydrogen bonds between cation and anion displayed an intermediate character between shared and closed-shell interactions. Additionally, comparison with previously reported similar TMP salts (CSD ref. code: CESRUN, HURMOW and PARWUB) demonstrated 3D-isostructural packing features in the crystal structure of the title salt.

Comparative Analysis of Nickel-Phosphine Complexes with Cumulated Double Bond Ligands: Structural Insights and Electronic Interactions via ETS-NOCV and QTAIM Approaches.

This study presents a comprehensive analysis of nickel-phosphine complexes, specifically Ni(PH3)2(OCCH2), Ni(PH3)2(H2CCO), Ni(PH3)2(H2CCCH2), Ni(PH3)2(NNCH2), and Ni(PH3)2(η1-H2CNN). Utilizing ETS-NOCV analysis, we explored orbital energy decomposition and the Hirshfeld charges of the ligands, providing insights into the electronic structures and donor-acceptor interactions within these complexes. The interactions in the ketene and allene complexes exhibit similar deformation densities and NOCV orbital shapes to those calculated for Ni(PH3)2(NNCH2), indicating consistent interaction characteristics across these complexes. The total interaction energy for all η2 complexes is observed to be over 60 kcal/mol, slightly exceeding that of the analogous carbon dioxide complex reported earlier. Furthermore, the study highlights the stronger back-donation as compared to donor interactions across all η2 complexes. This is further corroborated by Hirshfeld analysis, revealing the charge distribution dynamics within the ligand fragments. The research offers new perspectives on the electron distribution and interaction energies in nickel-phosphine complexes, contributing to a deeper understanding of their catalytic and reactive behaviors.

Implicit and Explicit Solvent Effects on the Global Reactivity and the Density Topological Parameters of the Preferred Conformers of Caespitate

In the search to cover the urgent need to combat infectious diseases, natural products have gained attention in recent years. The caespitate molecule, isolated from the plant Helichrysum caespititium of the Asteraceae family, is used in traditional African medicine. Caespitate is an acylphloroglucinol with biological activity. Acylphloroglucinols have attracted attention for treating tuberculosis due to their structural characteristics, highlighting the stabilizing effect of their intramolecular hydrogen bonds (IHBs). In this work, a conformational search for the caespitate was performed using the MM method. Posteriorly, DFT calculations with the APFD functional were used for full optimization and vibrational frequencies, obtaining stable structures. A population analysis was performed to predict the distribution of the most probable conformers. The calculations were performed in the gas phase and solution using the implicit SMD model for water, chloroform, acetonitrile, and DMSO solvents. Additionally, the multiscale ONIOM QM1/QM2 model was used to simulate the explicit solvent. The implicit and explicit solvent effects were evaluated on the global reactivity indexes using the conceptual-DFT approach. In addition, the QTAIM approach was applied to analyze the properties of the IHBs of the most energetically and populated conformers. The obtained results indicated that the most stable and populated conformer is in the gas phase, and chloroform has an extended conformation. However, water, acetonitrile, and DMSO have a hairpin shape. The optimized structures are well preserved in explicit solvent and the interaction energies for the IHBs were lower in explicit than implicit solvents due to non-covalent interactions formed between the solvent molecules. Finally, both methodologies, with implicit and explicit solvents, were validated with 1H and 13C NMR experimental data. In both cases, the results agreed with the experimental data reported in the CDCl3 solvent.

Double Centrosymmetric Si···π Tetrel Bonds as New Synthons─Evidence from Crystal Structures and DFT Calculations.

The crystal structure of bis((μ2-ethynylsilyloxo)-dichloro-aluminum), BEDCA, and a few related structures are characterized by the occurrence of tetrel bonds that link molecules. Particularly, centosymmetric dimers in such structures occur that are connected by two equivalent Si···π tetrel bonds. The dimer of BEDCA and dimers of other model species that similarly are linked by two equivalent Si···π tetrel bonds are analyzed theoretically. Some of the complexes calculated here are also characterized by the occurrence of triel bonds. Thus, ωB97XD/aug-cc-pVTZ calculations are performed and these DFT results are further supported by calculations with the use of other theoretical approaches: the quantum theory of atoms in molecules, QTAIM; the natural bond orbital, NBO; the energy decomposition analysis, EDA; and the noncovalent interactions method, NCI. The results show that the tetrel bonds analyzed here are rather weak, and they are not detected by the QTAIM approach; however, they are detected by other approaches, like NBO, for example. On the other hand, the triel bonds that occur in a few complexes discussed here are very strong and possess characteristics of covalent bonds.

A Holistic View of the Interactions between Electron-Deficient Systems: Clustering of Beryllium and Magnesium Hydrides and Halides.

In the search for common bonding patterns in pure and mixed clusters of beryllium and magnesium derivatives, the most stable dimers and trimers involving BeX2 and MgX2 (X = H, F, Cl) have been studied in the gas phase using B3LYP and M06-2X DFT methods and the G4 ab initio composite procedure. To obtain some insight into their structure, stability, and bonding characteristics, we have used two different energy decomposition formalisms, namely MBIE and LMO-EDA, in parallel with the analysis of the electron density with the help of QTAIM, ELF, NCIPLOT, and AdNDP approaches. Some interesting differences are already observed in the dimers, where the stability sequence observed for the hydrides differs entirely from that of the fluorides and chlorides. Trimers also show some peculiarities associated with the presence of compact trigonal cyclic structures that compete in stability with the more conventional hexagonal and linear forms. As observed for dimers, the stability of the trimers changes significantly from hydrides to fluorides or chlorides. Although some of these clusters were previously explored in the literature, the novelty of this work is to provide a holistic approach to the entire series of compounds by using chemical bonding tools, allowing us to understand the stability trends in detail and providing insights for a significant number of new, unexplored structures.

Ionization, intrinsic basicity, and intrinsic acidity of unsaturated diols of astrochemical interest: 1,1- and 1,2-ethenediol: A theoretical survey.

The structure, stability, and bonding characteristics of 1,1- and 1,2-ethenediol, their radical cations, and their protonated and deprotonated species were investigated using high-level ab initio G4 calculations. The electron density of all the neutral and charged systems investigated was analyzed using the QTAIM, ELF, and NBO approaches. The vertical ionization potential (IP) of the five stable tautomers of 1,2-ethenediol and the two stable tautomers of 1,1-ethenediol go from 11.81 to 12.27 eV, whereas the adiabatic ones go from 11.00 to 11.72 eV. The adiabatic ionization leads to a significant charge delocalization along the O-C-C-O skeleton. The most stable protonated form of (Z)-1,2-ethenediol can be reached by the protonation of both the anti-anti and the syn-anti conformers, whereas the most stable deprotonated form arises only from the syn-anti one. Both charged species are extra-stabilized by the formation of an O-H···O intramolecular hydrogen bond (IHB) which is not found in the neutral system. (Z)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its cis-glycolaldehyde isomer. The most stable protonated species of (E)-1,2-ethenediol comes from its syn-syn conformer, although the anti-anti conformer is the most basic one. Contrarily, the three conformers yield a common deprotonated species, so their acidity follows exactly their relative stability. Again, the (E)-1,2-ethenediol is predicted to be less stable, less basic, and more acidic than its trans-glycolaldehyde isomer. Neither the neutral nor the protonated or the deprotonated forms of 1,1-ethenediol show the formation of any O-H···O IHB. The most stable protonated species is formed by the protonation of any of the two tautomers, but the most stable deprotonated form arises exclusively from the syn-anti neutral conformer. The conformers of 1,1-ethenediol are much less stable and significantly less basic than their isomer, acetic acid, and only slightly more acidic.

A combined experimental and quantum chemical analysis of 3,3′-diaminodipropylamine–dihydrogenphosphate hybrid compound: [H3(C6H17N3)][(H2PO4)3

An organoammonium-dihydrogenphosphate compound, [H3(DADP)][(H2PO4)3], DADP = 3,3′-diaminodipropylamine was synthesized and characterized. The crystal structure consists of a supramolecular organic-inorganic framework mediated via strong charge-assisted N–H···O and O–H···O hydrogen bonding, and non-classical C–H···O H-bonds. The NCI and QTAIM approaches revealed the occurrence of the noteworthy C–H···Csp3 carbon-centered H-bonds, and the C–H···H–C dispersive contacts. Intermolecular interactions were further elucidated by Hirshfeld surfaces analysis. Moreover, dispersion-corrected Density Functional Theory (wB97X-D/aug-cc-pVTZ) provided insights into chemical reactivity properties. The compound was also analyzed using solid-state spectroscopies and thermal experiments. This contribution enhances the understanding of the structural diversity of organic-dihydrogenphosphate compounds.

(Ro)vibrational Spectroscopic Constants, Lifetime and QTAIM Evaluation of Fullerene Dimers Stability.

The iconic caged shape of fullerenes gives rise to a series of unique chemical and physical properties; hence a deeper understanding of the attractive and repulsive forces between two buckyballs can bring detrimental information about the structural stability of such complexes, providing significant data applicable for several studies. The potential energy curves for the interaction of multiple van der Waals buckyball complexes with increasing mass were theoretically obtained within the DFT framework at ωB97xD/6-31G(d) compound model. These potential energy curves were employed to estimate the spectroscopic constants and the lifetime of the fullerene complexes with the Discrete Variable Representation and with the Dunham approaches. It was revealed that both methods are compatible in determining the rovibrational structure of the dimers and that they are genuinely stable, i.e., long-lived complexes. To further inquire into the nature of such interaction, Bader's QTAIM approach was applied. QTAIM descriptors indicate that the interactions of these closed-shell systems are dominated by weak van der Waals forces. This non-covalent interaction character was confirmed by the RDG analysis scheme. Indirectly, QTAIM also allowed us to confirm the stability of the non-covalent bonded fullerene dimers. Our lifetime calculations have shown that the studied dimers are stable for more than 1 ps, which increases accordingly with the number of carbon atoms.

Enhanced extraction of phenolic compounds from mango by-products using deep eutectic solvents

Deep eutectic solvents (DESs) potential for the extraction of polyphenolic compounds (PC) from mango by-products (peel and seed) was evaluated. Ultrasound (US) and agitation were applied to evaluate the effects of solvent and extraction methodology. The extracts were characterized with antioxidant capacity and HPLC-DAD profile. A theoretical study was performed using density functional theory and the QTAIM approach. β-alanine and choline chloride based DESs were effective to extract PC from peel and seed. Some DES increased PC extraction up to three times for peel (23.05 ± 1.22 mg/g DW) and up to five time for seeds (60.01 ± 1.40 mg/g DW). The PC profile varied with the solvent (DES vs EtOH/MeOH), procedure (US vs agitation) and material (peel or seed). Mangiferin extraction from peels was significantly increased with β-alanine based DES (676.08 ± 20.34 μg/gDW). The strength of H-bonds had a determining effect on the viscosity of DESs. The solute-solvent solvation energy was suitable to estimate the strength of H-bond interactions between DES and target compounds. This study demonstrates the remarkable capacity of DESs to extract PC from mango by-products and provides insights into the factors controlling extraction properties.

Synthesis, Antifungal Evaluation of 3-[{(1-aminomethyl) -5,7-dimethyl-2- oxoindolin-3-ylidene} amino]-2-phenylquinazolin-4(3H)-ones and their NLO, MESP, Global Reactivity Descriptor, and AIM Study through DFT Approach

Abstract:A series of fused 3-[{(1-aminomethyl)-5,7-dimethyl-2-oxoindolin-3-ylidene}amino]-2- phenylquinazolin-4(3H)-ones 4(i-ix)) has been designed and synthesized by the condensation reaction between 3-amino -2-phenylquinazolin-4(3H)-one and 5,7-dimethylindolin-2,3-dione, followed by aminomethylation with secondary amines in the presence of formaldehyde and were also screened for their antifungal potential against human pathogenic fungi. The structures of all synthesized compounds have been established with the help of elemental and spectral analysis, such as NMR, FT-IR and mass spectrometry. Out of all synthesized compounds 4(i-ix), theoretical calculation was performed for 3-((5,7-dimethyl-1-(morpholinomethyl)-2-oxoindolin-3-ylidene)amino)-2-phenylquinazolin- 4(3H)-one (4i). The experimental 1H was compared with theoretically calculated values by using B3LYP/6-31G (d, p) level through the GIAO approach. The higher value of first-order hyper polarizability predicted (4i) may be used as NLO material. To explore molecular stability, three intermolecular interactions, such as N8—O22··· H47, C37—H64 ···N12, and C23—H45 ···C30, were observed through the QTAIM approach. In addition, global reactivity descriptor and molecular electrostatic potential were computed for the prediction of reactivity and reactive sites.

Tautomerization reactions of thiobarbituric acid: A detailed kinetic study using combined canonical variational transition state theory and QTAIM approach

AbstractThe kinetics of tautomerization reactions of thiobarbituric acid were thoroughly investigated at the B3LYP/6‐311+G(3df,2p) level of theory and elevated temperatures from 260 to 1000 K. The kinetic parameters were determined by employing canonical variational transition state theory (CVT). The quantum tunneling effect was included by centrifugal‐dominant small‐curvature semiclassical adiabatic ground‐state approximation method. Intrinsic reaction coordinate (IRC) analysis was performed to certify a unique connection from an obtained transition state configuration to optimized structures of reactant and products. The reaction forces and reaction force constants were computed across the IRC of each reaction. Then, using extremums of reaction forces, each reaction was partitioned into three stages containing reactant, transition state, and product stages. The extent of reactions was followed along with three reaction stages. The dependence of kinetic parameters and curvature of Arrhenius plots on temperature were investigated and discussed in the framework of CVT. To further unveil the mechanism of the reactions, the quantum theory of atoms in molecules was employed. To do this aim, QTAIM descriptors on the bond critical point (BCP) of involved bonds including the density of electrons, Laplacian of the density of electrons, Lagrangian kinetic energy, potential energy, and energy density were computed and surveyed along with reaction extent through IRC.

The quest of the most stable structure of a carboxyfullerene and its drug delivery limits: A DFT and QTAIM approach

Carboxyfullerenes have been widely used for medicinal applications. These classes of materials are known for their promising properties making them suitable for biological implementations. However, theoretical studies for the structural and electronic properties of these versatile carboxyl group attached nanocages seem rare. The definition of interaction points appears to require further enhancement. 5-Fluorouracil drug molecule is considered as the backbone of the most of chemotherapy regimens. Therefore, it deserves special attention. In this work, it was found that the interaction of carboxyl group occurs via adjacent carbon atoms on the hexagon of the surface of C60 and carboxyfullerenes might be suitable candidates for 5-Fluorouracil showing partially covalent interactions for possible drug delivery applications.

Electrical conductivity of diene and pheneMolecular Nanowires: A QTAIM approach

Electrical conductivity of diene and pheneMolecular Nanowires: A QTAIM approach

Exploring the intermolecular interactions in Co-crystals of 4-cyanopyridine with 4-bromobenzoic acid: Experimental and computational methods

In present work, we have performed synthesis, quantitative and qualitative analysis of the different intermolecular interactions present in 4-Cyanopyridine:4-bromobenzoic acid(1:1) Co-crystal. The single crystal X-ray diffraction confirms the Co-crystal crystallizes in the P1¯ space group with one molecule of 4-cyanopyridine and 4-bromobenzoic acid in the asymmetric unit. The Co-crystal is mainly stabilized by presence of strong C-H…O and O-H…N interactions. Computational studies confirms, along with strong hydrogen bonds C-H…Br, C-H…N, N…Br and π…π interactions plays a significant role in stabilizing the crystal packing. Lattice energy of the compound is calculated using PIXEL method. Hirshfeld surface analysis and fingerprint plots helped in analysing percentage contribution of each intermolecular interaction towards crystal packing. Topological properties of intermolecular interactions are studied based on QTAIM approach. CSD studies shows presence of isostructural polymorph of 4-Cyanopyridine:4-bromobenzoic acid Co-crystal. Later both polymorphs are compared using different computational tools.

X-ray Structures and Computational Studies of Two Bioactive 2-(Adamantane-1-carbonyl)-N-substituted Hydrazine-1-carbothioamides

Two biologically active adamantane-linked hydrazine-1-carbothioamide derivatives, namely 2-(adamantane-1-carbonyl)-N-(tert-butyl)hydrazine-1-carbothioamide) 1 and 2-(adamantane-1-carbonyl)-N-cyclohexylhydrazine-1-carbothioamide 2, have been synthesized. X-ray analysis was conducted to study the effect of the t-butyl and cyclohexyl moieties on the intermolecular interactions and conformation of the molecules in the solid state. X-ray analysis reveals that compound 1 exhibits folded conformation, whereas compound 2 adopts extended conformation. The Hirshfeld surface analysis indicates that the contributions of the major intercontacts involved in the stabilization of the crystal structures do not change much as a result of the t-butyl and cyclohexyl moieties. However, the presence and absence of these contacts is revealed by the 2D-fingerprint plots. The CLP-Pixel method was used to identify the energetically significant molecular dimers. These dimers are stabilized by different types of intermolecular interactions such as N-H···S, N-H···O, C-H···S, C-H···O, H-H bonding and C-H···π interactions. The strength of these interactions was quantified by using the QTAIM approach. The results suggest that N-H···O interaction is found to be stronger among other interactions. The in vitro assay suggests that both compounds 1 and 2 exhibit urease inhibition potential, and these compounds also display moderate antiproliferative activities. Molecular docking analysis shows the key interaction between urease enzyme and title compounds.

Explaining the High Catalytic Activity in Bis(indenyl)methyl Zirconium Cation Using Combined EDA-NOCV/QTAIM Approach.

The main purpose of this study is to elucidate some discrepancies already observed in the catalytic activity values of some zirconocene methyl cations. The EDA-NOCV scheme was employed for a theoretical description of the interactions between an ethylene molecule and five catalysts of zirconocene methyl cation. The nature of the chemical interactions has been elucidated through the QTAIM topological analysis. The steric hindrance due to the ligands was evaluated qualitatively by means of an IRI-based analysis and quantitively through Fisher information. The findings prove that the indenyl ligand seems to favor the orbital interaction between the ethylene molecule and the metal centre of zirconocene methyl cation. Both electrostatic and orbital contributions play a crucial role in stabilising the studied complexes. Based on the NOCV deformation density contributions, the strongest orbital interaction is reached with the bis(indenyl)methyl zirconium cation, which is the only one exhibiting covalent interactions. Especially, the strong contribution of π-back donation (occurring from the occupied orbitals of the zirconium atom to the π* anti-bonding orbital of ethylene) may be a key to understand why this catalyst has a higher polymerisation yield than the other studied catalysts. This work suggests a perspective for predicting values of catalytic activity when theoretically designing novel catalysts of zirconocene type.

Density functional analysis of conducting molecules: A Theoretical Investigation via QTAIM approach

The assessment of quaterphenyl and quarter (1,4 dithiine) molecules joining the spatial dissemination of electron inside the framework, was finished using Density Functional analysis incorporated with LANL2DZ premise set joined with the Bader's AIM theory. All the examinations were carried out within growing electric field from 0.05–0.26VÅ−1. The chemical nature and the topological assessment of the nano wire were studied in detail by subjecting the same to external electric field to prove the possible commercial importance of the structure in the field of nanoelectronics. HOMO-LUMO assessment was made to choose the way in which the one-dimensional nanowires show conductivity. The I-V characteristic plot and ESP surface were generated to study the conducting nature of the nanowires.

NCI Study of the Influence of Steric Hindrance on the Conformational Isomers of Propane, Butane, and Ethane Derivatives

AbstractThe role of the steric clash in the rotational energy barrier in CX3CX3 (X=H, CH3, F), propane, and butane compounds was studied using the NCI method and QTAIM approach. We found that the values of the repulsive density integral of NCI agrees with the traditional chemical steric model, as it increases with the size of the substituent. However, not in every case studied here, was the steric clash identified as the origin of the energy barrier. In the ethane case we note the absence of repulsive and attractive NCI across the full spectrum of the dihedral angles studied, whereas only in the propane and butane cases are the results consistent with the classical picture of the steric clash being the origin of the energy barrier. The energy profile for 2,2,3,3‐tetramethylbutane shows two energy barriers of 8.7 kcal/mol and 0.96 kcal/mol, their origin was analysed in terms of the alkyl‐alkyl interactions.