Are Bond Critical Points Really Critical for Hydrogen Bonding?

Using correlation plots of binding energy and electron density at the bond critical point, we investigated the nature of intermolecular non-covalent bonds (D-X⋯A, where D = O/S/F/Cl/Br/H, mostly, X = main group elements (except noble gases), A = H2O, NH3, H2S, PH3, HCHO, C2H4, HCN, CO, CH3OH, and CH3OCH3). The binding energies were calculated at the MP2 level of theory, followed by Atoms in Molecules (AIM) analysis of the ab initio wave functions to obtain the electron density at the bond critical point (BCP). For each non-covalent bond, the slopes of the binding energy versus electron density plot have been determined. Based on their slopes, non-covalent bonds are classified as non-covalent bond closed-shell (NCB-C) or non-covalent bond shared-shell (NCB-S). Intriguingly, extrapolating the slopes of the NCB-C and NCB-S cases leads to intramolecular "ionic" and "covalent" bonding regimes, establishing a link between such intermolecular non-covalent and intramolecular chemical bonds. With this new classification, hydrogen bonds and other non-covalent bonds formed by a main-group atom in a covalent molecule are classified as NCB-S. Atoms found in ionic molecules generally form NCB-C type bonds, with the exception of carbon which also forms NCB-C type bonds. Molecules with a tetravalent carbon do behave like ions in ionic molecules such as NaCl and interact with other molecules through NCB-C type bonds. As with the chemical bonds, there are some non-covalent bonds that are intermediate cases.

The complexes formed as a result of the interactions between cyanophosphine (CP, H2PCN) and hypohalous acid molecules (HOX, X = F, Cl, Br, and I) were studied by employing ab initio computations conducted at the MP2/aug-cc-pVTZ level. Three types of complexes were acquired (I, II, and III) as a result of the (O∙∙∙P) pnicogen bond, the (N∙∙∙H) hydrogen bond, and the (N∙∙∙X) halogen bond interaction, respectively. The results of harmonic vibrational frequency calculations with no imaginary frequencies confirmed the structures as minima. In addition, given the interaction energy of the complexes, hydrogen bond complexes of structure II have the highest stability compared to other structures. In all studied complexes, the strength of the interactions depended on the electronegativity of the halogen atoms. The characteristics and nature of the whole three types of complexes were examined and evaluated with natural bond orbital (NBO), atom in molecules (AIM), molecular electrostatic potential (MEP) maps, non-covalent interaction (NCI) index, and electron density difference (EDD) analyses. The optimization of all complexes and corresponding monomers was conducted through the ab initio method, employing the MP2 level along with the aug/cc-pVTZ basis set for all atoms, except for the iodine (I) atom, for which the aug-cc-pVTZ (PP) basis set was employed. Subsequent frequency calculations were executed to ascertain the minimum energy state of the complexes at the MP2 level and the aug/cc-pVTZ basis set, utilizing Gaussian09 software. The MEP maps of the monomers were generated using the analysis-surface suite (WFA-SAS) software package. To probe the orbital interactions within the studied complexes, NBO analysis was performed employing NBO software. The assessment of bond nature, topological features, and electron density values at critical points for the studied complexes was undertaken using AIMAll software. The NCI index was derived utilizing Multiwfn software, and its three-dimensional representation was rendered using VMD software.

The nature of bifurcated or three-centered hydrogen bonds (HB) has been investigated. Different families of compounds were chosen: monomers with intramolecular three-centered HB, dimers with a HB donor (HBD) and a molecule with two HB acceptor (HBA) groups, and trimers with one HBD and two HBAs. All the systems were optimized at the B3LYP/6-31G* level, and, in the case of the complexes, the interaction energies were evaluated and corrected with the basis set superposition error (BSSE). The electronic nature of these three-centered HBs was analyzed by means of the atoms in molecules (AIM) approach. The present study indicates the existence of bifurcated bond paths in the AIM analysis with electron densities that can be classified as follows: (i) compounds with symmetric three-centered HBs presenting two symmetric bond critical points with equal values of electron density; (ii) compounds with asymmetric three-centered HBs presenting two bond critical points with different values of electron density; (iii) compounds with a regular HB and a van der Waals interaction showing two bond critical points with different electron density values one of which is very small; (iv) van der Waals complexes with two bond critical points having very small electron densities. Therefore, looking at the geometry, electron density, and energy results, the nature as HB of these three-centered interactions has been confirmed.

Closed-shell contacts between two copper(I) ions are expected to be repulsive. However, such contacts are quite frequent and are well documented. Crystallographic characterization of such contacts in unsupported and bridged multinuclear copper(I) complexes has repeatedly invited debates on the existence of cuprophilicity. Recent developments in the application of Bader's theory of atoms-in-molecules (AIM) to systems in which weak hydrogen bonds are involved suggests that the copper(I)-copper(I) contacts would benefit from a similar analysis. Thus the nature of electron-density distributions in copper(I) dimers that are unsupported, and those that are bridged, have been examined. A comparison of complexes that are dimers of symmetrical monomers and those that are dimers of two copper(I) monomers with different coordination spheres has also been made. AIM analysis shows that a bond critical point (BCP) between two Cu atoms is present in most cases. The nature of the BCP in terms of the electron density, ρ, and its Laplacian is quite similar to the nature of critical points observed in hydrogen bonds in the same systems. The ρ is inversely correlated to Cu-Cu distance. It is higher in asymmetrical systems than what is observed in corresponding symmetrical systems. By examining the ratio of the local electron potential-energy density (V(c)) to the kinetic energy density (G(c)), |V(c)|/G(c) at the critical point suggests that these interactions are not perfectly ionic but have some shared nature. Thus an analysis of critical points by using AIM theory points to the presence of an attractive metallophilic interaction similar to other well-documented weak interactions like hydrogen bonding.

Ab initio calculations have been performed on single‐electron halogen bonds between methyl radical and bromine‐containing molecules to gain a deeper insight into the nature of such noncovalent interactions. Bader's atoms in molecules (AIM) theory have also been applied to the analysis of the linking of the single‐electron halogen bond. Various characteristics of the RBr…CH3 interaction, i.e., binding energies, geometrical parameters and topological properties of the electron density have been determined. The presence of the bond critical points (BCPs) between the bromine atom and methyl radical and the values of electron density and Laplacian of electron density at these BCPs indicate the closed‐shell interactions in the complexes. The single‐electron halogen bonds, which are significantly weaker than the normal halogen bonds, exhibit equally bond strength as compared to the single‐electron hydrogen bond. It has been also found that plotting of the binding energies versus topological properties of the electron density at the BCPs gives two straight lines. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

This study aims to cast light on the nature of hydrogen bonds and their cooperativity that exists in alcohol-water ( ROH ( H 2 O ) n ) ( R = − C H 3 ( − Me ) , − C H 2 C H 3 ( − Et ) ) (n = 1–10) clusters using atoms in molecules (AIM) theory and symmetry-adapted perturbation theory (SAPT). The investigation of optimum structures suggests that alcohol ( ROH ) forms two hydrogen bonds, one primary hydrogen bond ( O − H ⋅ ⋅ ⋅ O ) , and one secondary hydrogen bond ( C − H ⋅ ⋅ ⋅ O ) Two types of hydrogen bonds are addressed in these studies, where alcohol works as the hydrogen bond donor ( ROH ⋅ ⋅ ⋅ O H 2 ) and hydrogen bond acceptor ( RHO ⋅ ⋅ ⋅ HOH ) . The AIM results reveal that RHO ⋅ ⋅ ⋅ HOH and ROH ⋅ ⋅ ⋅ O H 2 hydrogen bonds are partially covalent. The SAPT study demonstrates that in all the clusters studied herein, the electrostatic interaction between alcohol and water is the main attractive force, and its contribution may be two times larger than the separate corresponding contributions from the dispersion and the induction terms. The electron density (ρ) at the bond critical point (BCP) is a suitable parameter to assess the strength of the interaction. The current study shows the strength and nature of ROH ⋅ ⋅ ⋅ O H 2 and RHO ⋅ ⋅ ⋅ HOH hydrogen bond, and cooperative effect in ( ROH ( H 2 O ) n ) ( R = − C H 3 ( − Me ) , − C H 2 C H 3 ( − Et ) .) (n = 1–10).

The source function (SF) decomposes the electron density at any point into contributions from all other points in the molecule, complex, or crystal. The SF "illuminates" those regions in a molecule that most contribute to the electron density at a point of reference. When this point of reference is the bond critical point (BCP), a commonly used surrogate of chemical bonding, then the SF analysis at an atomic resolution within the framework of Bader's Quantum Theory of Atoms in Molecules returns the contribution of each atom in the system to the electron density at that BCP. The SF is used to locate the important regions that control the hydrogen bonds in both Watson-Crick (WC) DNA dimers (adenine:thymine (AT) and guanine:cytosine (GC)) which are studied in their neutral and their singly ionized (radical cationic and anionic) ground states. The atomic contributions to the electron density at the BCPs of the hydrogen bonds in the two dimers are found to be delocalized to various extents. Surprisingly, gaining or loosing an electron has similar net effects on some hydrogen bonds concealing subtle compensations traced to atomic sources contributions. Coarser levels of resolutions (groups, rings, and/or monomers-in-dimers) reveal that distant groups and rings often have non-negligible effects especially on the weaker hydrogen bonds such as the third weak CH⋅⋅⋅O hydrogen bond in AT. Interestingly, neither the purine nor the pyrimidine in the neutral or ionized forms dominate any given hydrogen bond despite that the former has more atoms that can act as source or sink for the density at its BCP. © 2018 Wiley Periodicals, Inc.

DFT, spectroscopic, DSC/TGA, electronic, biological and molecular docking investigation of 2,5-thiophenedicarboxylic acid: A promising anticancer agent

Describing non-covalent interactions (NCIs) has shown to be of paramount importance in many areas of theoretical chemistry and related disciplines, such as biochemistry and material science. However, non-covalent interactions are subtle effects, very difficult to reproduce from most common computational approaches. Electron density studies have shown to provide a good semiquantitative visual approach to such interactions, which are much less prone to method dependency. But to which extent? This is the question addressed in this contribution. The NCI approach based on the reduced density gradient is given the third degree so as to provide the user with a benchmark on how it is affected by the computational method and the basis set of choice. We have assessed the dependence of the NCI results on the geometry. This last question is addressed in detail to dissect how, why and when the NCI method can be used to understand dispersion interactions. Along various examples, we will show that the NCI index is very little dependent on the method and basis set used in the calculation of the electron density as long as the geometry is kept fixed. Indeed, the biggest variations in NCI come from changes in the geometry. Thus, methods which provide descriptions of a given interaction type of different accuracies will yield different electron density organizations. This gives no qualitative variations in the NCI 3D picture. But it is reflected in quantitative NCI measures even in very subtle cases. Moreover, in the case of a failure of the calculation method, NCI can also reveal the sources of its error. NCI volumes are able to locate the energetic ordering in various conformational situations, but always in a relative manner. Absolute values should not be used in comparisons, nor between compounds that do not belong to the same family.

Intramolecular halogen bonds have been the subject of several current experimental and theoretical studies. In this work, intramolecular halogen bonds in a series of 1,2-aryldiyne molecules were investigated using density functional theory calculations at the M06-2x level of theory. For comparison, some dimeric complexes between halogenated aryldiynes and quinolinyl compounds were also considered. The calculated interatomic distances and interaction angles of intramolecular halogen bonds compare fairly well with those determined experimentally, and the triangle motifs retain almost perfectly planar in all the studied molecules. Many of the well-known properties of conventional halogen bonds are reproduced in intramolecular halogen bonds: the interaction strength tends to increase with the enlargement of the atomic radius of halogens (I > Br > Cl); the attachment of electron-withdrawing moieties to halogens leads to much stronger intramolecular halogen bonds; the X···N (quinolinyl) interactions are stronger than the X···O (carbonyl) halogen bonds. On the basis of the shorter interatomic distances and the larger values of electron densities at the bond critical points, intramolecular halogen bonds become stronger in strength than corresponding intermolecular halogen bonds. However, these interactions have similar structural, energetic, atoms in molecules (AIM), and noncovalent interaction index (NCI) characteristics to traditional halogen bonds. Therefore, these interactions can be recognized as halogen bonds that are primarily electrostatic in nature. Particularly, the formation of intramolecular halogen bonds gives rise to the essential coplanarity of the molecules, whereas the two subunits in the dimeric complexes deviate from planarity to a large degree. In addition, a small number of crystal structures containing intramolecular halogen bonds were retrieved from the Cambridge Structural Database (CSD), to provide more insights into these interactions in crystals. This work not only will extend the knowledge of noncovalent interactions involving halogens as electrophilic centers but also could be very useful in molecular design and synthetic chemistry.

A computational study of the monomers and hydrogen-bonded dimers of 2-pyrrolidone was executed at different DFT levels and basis sets. The above dimeric complexes were treated theoretically to elucidate the nature of the intermolecular hydrogen bonds, geometry, thermodynamic parameters, interaction energies, and charge transfer. The processes of dimer formation from monomers and concerted reactions of double proton transfer were considered. The evolution of geometry, vibrational frequencies, charge distribution, and AIM properties in going from monomers to dimers was systematically followed. The solvent effects upon dimer formation were investigated in terms of the self-consistent reaction field (SCRF Onsager model). For the monomers and three dimers, vibrational frequencies were calculated and the changes in frequencies of the vibrations most sensitive to complexation were discussed. The orbital interactions were shown to lengthen the X-H (X = N, O) bond and lower its vibrational frequency (a red shift). To better understand the nature of the corresponding intermolecular interactions, we performed natural bond orbital (NBO) analysis. Topological analysis of electron density at bond critical points (BCP) was executed for complex molecules using the Bader's atoms in molecules (AIM) theory. The interaction energies were calculated, and the basis set superposition errors (BSSE) were estimated systematically. Satisfactory correlations between the structural parameters, interaction energies, and electron density characteristics at BCP were found.

The chemical nature of very strong hydrogen bonds in some categories of compounds

Experimental and theoretical electron density distribution of α,α-trehalose dihydrate

The hydrogen bonding interactions of the HNO dimer have been investigated using ab initio molecular orbital and density functional theory (DFT) with the 6-311++G(2d,2p) basis set. The natural bond orbital (NBO) analysis and atom in molecules (AIM) theory were applied to understand the nature of the interactions. The interrelationship between one N-H...O hydrogen bond and the other N-H...O hydrogen bond has been established by performing partial optimizations. The dimer is stabilized by the N-H...O hydrogen bonding interactions, which lead to the contractions of N-H bonds as well as the characteristic blue-shifts of the stretching vibrational frequencies nu(N-H). The NBO analysis shows that both rehybridization and electron density redistribution contribute to the large blue-shifts of the N-H stretching frequencies. A quantitative correlations of the intermolecular distance H...O (r(H...O)) with the parameters: rho at bond critical points (BCPs), s-characters of N atoms in N-H bonds, electron densities in the sigma*(N-H), the blue-shift degrees of nu(N-H) are presented. The relationship between the difference of rho (|Deltarho|) for the one hydrogen bond compared with the other one and the difference of interaction energy (DeltaE) are also illustrated. It indicates that for r(H...O) ranging from 2.05 to 2.3528 A, with increasing r(H...O), there is the descending tendency for one rho(H...O) and the ascending tendency for the other rho(H...O). r(H...O) ranging from 2.3528 to 2.85 A, there are descending tendencies for the two rho(H...O) with increasing r(H...O). On the potential energy surface of the dimer, the smaller the difference between one rho(H...O) and the other rho(H...O) is, the more stable the structure is. As r(H...O) increases, the blue-shift degrees of nu(N-H) decrease. The cooperative descending tendencies in s-characters of two N atoms with increasing r(H...O) contribute to the decreases in blue-shift degrees of nu(N-H). Ranging from 2.05 to 2.55 A, the increase of the electron density in one sigma*(N-H) with elongating r(H...O) weakens the blue-shift degrees of nu(N-H), simultaneously, the decrease of the electron density in the other sigma*(N-H) with elongating r(H...O) strengthens the blue-shift degrees of nu(N-H). Ranging from 2.55 to 2.85 A, the cooperative ascending tendencies of the electron densities in two sigma*(N-H) with increasing r(H...O) contribute to the decreases in blue-shift degrees of nu(N-H).

Toxic agents in the environment represent a serious threat to human life and pose a major problem, which has led scientists to conduct continuous research into methods for detecting and removing them from the environment. For example, H₂S, SO₂, NH₃, CO, CO₂, NO, and NO₂ are toxic agents commonly found in their gaseous state. Enhancing environmental sensing is, therefore, essential for protecting the ecosystem. In this context, we suggest new complexes of copper and cobalt based on thymine base pair: [thym-Co-thym] and [thym-Cu-thym] as sensors to detect and to attract toxic agents. Our theoretical study demonstrates the potential of the proposed complexes to act as biosensors capable of capturing toxic agents from the environment, as supported by various quantum chemistry methods, including quantum theory of atoms in molecules (QTAIM), reduced density gradient (RDG), natural bond orbitals (NBO), and non-covalent interaction (NCI) analysis. Orbital interaction is favored for H2S (0.06eV, 0.04eV) and NO (0.24eV, 0.35eV) for both complexes [thym-Co-thym] and [thym-Cu-thym] respectively. Energetically, interaction of [thym-Co-thym] and [thym-Cu-thym] is more favorable with SO2 (- 319.9kcal/mol, - 332.5kcal/mol respectively) than with the other agents. According to the RDG (reduced density gradient) method, the values of (signλ2) ρ(r) where λ2 is the second eigenvalue of the electron density Hessian matrix, are negative with ρ(r) > 0. This indicates strong attractive non-covalent interactions such as hydrogen bonding and halogen bonding between the complexes and the toxic agents, case of HCN with thym-Cu-thym and NO with thym-Co-thym. Most of the other interactions between the complexes and the toxic agents are of the van der Waals type, as (sign λ2) ρ(r)≈0. The quantum theory of atoms in molecules (QTAIM) confirms the interactions between the proposed complexes and the toxic agents through the appearance of bond critical points (BCPs). The topological analysis of the Laplacian of the electron density ρ(r), the electron density ρ(r), and the total electronic energy density H(r) at these BCPs indicates that the interactions between the complexes and the toxic agents are predominantly classified as pure closed-shell interactions, except in the case of NO and NO₂, which exhibit partial covalent character with both cobalt and copper complexes. Quantum theory of atoms in molecules is in accord with reduced density gradient (RDG) in description of non-covalent interactions. All these factors could support the environmentally sustainable synthesis of these molecules as biosensors. Interaction of the two complexes with adducts increases the hardness (η) values. Softness decreases after interaction with adducts. The electronegativity (χ) and electrophilicity (ω) are decreased after interacting with adducts, so that the ability to capture one or more electrons will be reduced. Most of donor-acceptor orbitals fortify the interaction of different adducts with both of [thym-Co-thym] and [thym-Cu-thym] complexes. [thym-Co-thym] complex exhibits best detection of NO2 and NO by a broad rise at 400-500nm and of SO2 through an intensity jump blue-shift in the UV, while [thym-Cu-thym] complex detects H2S and HCN by strong band at almost 470-500nm. CO2 is weakly interacting in both complexes. At 200-400nm region [thym-Co-thym] shows well detection of SO2, H2S, CO2, CO, and HCN, whereas [thym-Cu-thym] indicates well detection of NO, CO, CO2, H2S, and SO2. Studied structures are optimized at DFT/M06-2x/6-311 + G(d,p) level of theory implemented in Gaussian16. The pseudopotential LanL2DZ is used for metals copper and cobalt. [thym-Cu-thym] and [thym-Co-thym] complexes are reoptimized toward considered species and in the presence of humidity (H2O molecule) at the same level of theory. Relativistic effects are taken through the fourth-(DKH4) and zeroth-order Douglas-Kroll-Hess (DKH0) approximations applying cc-pVDZ-DK basis set, spin-orbit effects are taken into account through DKHSO. Frequency calculations give real frequencies confirming the stability of the two complexes and ensure that the structures correspond to the lowest potential energy. Natural bond orbital (NBO) was performed at the same way using the version implemented in Gaussian16. All optimized structures were analyzed using VMD (visual molecular dynamics). The reduced density gradient (RDG) method was applied, and the function sign(λ₂)ρ(r) was requested to identify the type of non-covalent interaction between the complexes and the adducts (toxic agents). RDG scatter plots are drawn by multiwfn program and colored using gnuplot for improved visualization. Furthermore, the quantum theory of atoms in molecules (QTAIM) analysis confirmed the non-covalent interactions between complexes and adducts (toxic agents). UV-Vis absorption spectra of the all studied complexes were obtained by TD-DFT at the same level of theory TD-SCF/ M602x/6-311G** level of theory.