Interacting Quantum Atoms Research Articles

Interacting Quantum Atoms and Multipolar Electrostatic Study of XH···π Interactions.

The interaction energies of nine XH···π (X = C, N, and O) benzene-containing van der Waals complexes were analyzed, at the atomic and fragment levels, using QTAIM multipolar electrostatics and the energy partitioning method interacting quantum atoms/fragment (IQA/IQF). These descriptors were paired with the relative energy gradient method, which solidifies the connection between quantum mechanical properties and chemical interpretation. This combination provides a precise understanding, both qualitative and quantitative, of the nature of these interactions, which are ubiquitous in biochemical systems. The formation of the OH···π and NH···π systems is electrostatically driven, with the Qzz component of the quadrupole moment of the benzene carbons interacting with the charges of X and H in XH. There is the unexpectedly intramonomeric role of X-H (X = O, N) where its electrostatic energy helps the formation of the complex and its covalent energy thwarts it. However, the CH···π interaction is governed by exchange-correlation energies, thereby establishing a covalent character, as opposed to the literature's designation as a noncovalent interaction. Moreover, dispersion energy is relevant, statically and in absolute terms, but less relevant compared to other energy components in terms of the formation of the complex. Multipolar electrostatics are similar across all systems.

Borotropy: The Mechanism of Boron Transfer Between Adjacent N‐Atoms of Pyrazol‐1‐yl Rings

AbstractThis work examines theoretically the problem of the migration of borane groups between the nitrogen atoms of pyrazolyl rings. We have studied as a model the BH2 pyrazol‐1‐yl derivatives to determine the effects of substituents on the pyrazole ring; also 1‐(9‐borabicyclo[3.3.1]nonan‐9‐yl)‐1H‐pyrazoles to compare the calculated barriers with the experimental ones as well as to determine steric effects, i. e., how the buttressing effect increases the rate. The interacting quantum atoms methodology has been used for partitioning the energy of the systems in their stationary points into the contribution of pyrazole and BH2 group and their mutual interaction.

Enhanced Hydrogen Bonds of the (H2O)n (n = 4-8) Clusters Confined in Uranyl Peroxide Cluster Na20(UO2)20(O2)30.

Water is a basic resource and an essential component of living organisms. It often exhibits some novel properties under confinement. The water clusters (H2O)n (n = 4-8) confined in the cavity of uranyl peroxide cluster Na20(UO2)20(O2)30 (U20) have been computationally investigated by using ab initio molecular dynamics (AIMD) simulations and density functional theory (DFT) calculations in this study. The results show that the confined water clusters can form hydrogen bonds with the internal oxygen atoms (Ouranyl) of U20, and their conformations changed significantly. The average lengths (2.553-2.645 Å) of hydrogen bonds in confined (H2O)n are shorter than those (2.731-2.841 Å) in the corresponding free water clusters. Moreover, these confined hydrogen bonds show better hydrogen bond patterns according to the quantified indices. The natural bond orbital (NBO) calculations determine that there is electron transferring from the U20 to its interior (H2O)n. It is the main reason for enhancing hydrogen bond interactions among the confined water molecules because their oxygen atoms are more negatively charged and their hydrogen atoms are more positively charged. The quantum theory of atoms in molecules (QTAIM) and interacting quantum atoms (IQA) analyses indicate that the confined hydrogen bonds are more covalent, based on the significant electron density ρ(r) and local energy density H(r) at the bond critical points (BCPs), and the stronger energies of interatomic exchange interactions (Vxc). These findings may help to promote the communication of confined water clusters and enrich the understating of confined hydrogen bonds.

How to Compute Atomistic Insight in DFT Clusters: The REG-IQA Approach.

The relative energy gradient (REG) method is paired with the topological energy partitioning method interacting quantum atoms (IQA), as REG-IQA, to provide detailed and unbiased knowledge on the intra- and interatomic interactions. REG operates on a sequence of geometries representing a dynamical change of a system. Its recent application to peptide hydrolysis of the human immunodeficiency virus-1 (HIV-1) protease (PDB code: 4HVP) has demonstrated its full potential in recovering reaction mechanisms and through-space electrostatic and exchange-correlation effects, making it a compelling tool for analyzing enzymatic reactions. In this study, the computational efficiency of the REG-IQA method for the 133-atom HIV-1 protease quantum mechanical system is analyzed in every detail and substantially improved by means of three different approaches. The first approach of smaller integration grids for IQA integrations reduces the computational overhead by about a factor of 3. The second approach uses the line-simplification Ramer-Douglas-Peucker (RDP) algorithm, which outputs the minimal number of geometries necessary for the REG-IQA analysis for a predetermined root mean squared error (RMSE) tolerance. This cuts the computational time of the whole REG analysis by a factor of 2 if an RMSE of 0.5 kJ/mol is considered. The third approach consists of a "biased" or "unbiased" selection of a specific subset of atoms of the whole initial quantum mechanical model wave-function, which results in more than a 10-fold speed-up per geometry for the IQA calculation, without deterioration of the outcome of the REG-IQA analysis. Finally, to show the capability of these approaches, the findings gathered from the HIV-1 protease system are also applied to a different system named haloalcohol dehalogenase (HheC). In summary, this study takes the REG-IQA method to a computationally feasible and highly accurate level, making it viable for the analysis of a multitude of enzymatic systems.

Exact decompositions of the total KS-DFT exchange-correlation energy into one- and two-center terms.

In the so-called Interacting Quantum Atoms (IQA) approach, the molecular energy is numerically decomposed as a sum of atomic and diatomic contributions. While proper formulations have been put forward for both Hartree-Fock and post-Hartree-Fock wavefunctions, this is not the case for the Kohn-Sham density functional theory (KS-DFT). In this work, we critically analyze the performance of two fully additive approaches for the IQA decomposition of the KS-DFT energy, namely, the one from Francisco et al., which uses atomic scaling factors, and that from Salvador and Mayer based upon the bond order density (SM-IQA). Atomic and diatomic exchange-correlation (xc) energy components are obtained for a molecular test set comprising different bond types and multiplicities and along the reaction coordinate of a Diels-Alder reaction. Both methodologies behave similarly for all systems considered. In general, the SM-IQA diatomic xc components are less negative than the Hartree-Fock ones, which is in good agreement with the known effect of electron correlation upon (most) covalent bonds. In addition, a new general scheme to minimize the numerical error of the sum of two-electron energy contributions (i.e., Coulomb and exact exchange) in the framework of overlapping atoms is described in detail.

Merging the Energy Decomposition Analysis with the Interacting Quantum Atoms Approach.

Energy decomposition analysis (EDA) is a well-established approach to dissect the interaction energy into chemically sound components. Despite the inherent requirement of reference states has been a long-standing object of debate, the direct relation with the molecular orbital analysis helps in building up predictive models. The alternative molecular energy decomposition schemes that decompose the total energy into atomic and diatomic contributions, such as the interacting quantum atoms (IQA), has no external reference requirements and also the intra- and intermolecular interactions are treated on equal footing. However, a connection with heuristic chemical models are limited, bringing about a somewhat narrower predictive power. While efforts to reconcile the bonding picture obtained by both methodologies have been discussed in the past, a synergic combination of them has not been tackled yet. Herein, we present the use of IQA decomposition of the individual terms arising from the EDA in the context of intermolecular interactions, henceforth EDA-IQA. The method is applied to a molecular set covering a wide range of interaction types, including hydrogen bonding, charge-dipole, π-π and halogen interactions. We find that the electrostatic energy from EDA, entirely seen as intermolecular, leads to meaningful and non-negligible intra-fragment contributions upon IQA decomposition, originated from charge penetration. EDA-IQA also affords the decomposition of the Pauli repulsion term into intra- and inter-fragment contributions. The intra-fragment term is destabilizing, particularly for the moieties that are net acceptors of charge, while the inter-fragment Pauli term is actually stabilizing. In the case of the orbital interaction term, the sign and magnitude of the intra-fragment contribution at equilibrium geometries is largely driven by the amount of charge transfer, while the inter-fragment contribution is clearly stabilizing. EDA-IQA terms show a smooth behavior along the intermolecular dissociation path of selected systems. The new EDA-IQA methodology provides a richer energy decomposition scheme that aims at bridging the gap between the two main distinct real-space and Hilbert-space methodologies. Via this approach, the partitioning can be used directionally on all the EDA terms aiding in identifying the causal effects on geometries and/or reactivity.

Cooperativity and intermolecular hydrogen bonding in donor‐acceptor complexes of phenol and polyhydroxybenzenes

AbstractCooperativity between intermolecular and intramolecular hydrogen bonds is an important factor determining the strength of donor‐acceptor complexes. Its impact in poly‐1,2‐diols, notably polyhydroxybenzenes, is subject to debate. Density functional theory calculations have been performed on complexes of phenol, catechol, pyrogallol and 1,2,3,4‐tetrahydroxybenzene with pyridine, trimethylamine and trimethylphosphine oxide. Binding energies, proton NMR shifts, Quantum Theory of Atoms in Molecules analysis and Interacting Quantum Atoms (IQA) interaction energies reveal a positive cooperative effect of a topological intramolecular hydrogen bond (IMHB) in catechol relative to phenol, with insignificant or small negative effects of further HO groups. Except for catechol complexes, there are no topological IMHBs in any donors or their complexes, although all show Non‐Covalent Interaction isosurfaces. The absence of a topological IMBH in catechol itself is explained by electron density contour plots. Complexes of Me3N and Me3PO with catechol, pyrogallol and 1,2,3,4‐tetrahydroxybenzene display additional intermolecular hydrogen bonds, C‐H…H‐C and C‐H…O=P, respectively, with the hydrogen atom ortho to the bound HO group. The predominantly covalent or electrostatic character of the various hydrogen bond types is discussed in terms of the IQA energy partition scheme, which is also useful for characterising IMHBs in the absence of a bond critical point. These results further our understanding of the nature and the limits of cooperative hydrogen bonding in donor‐acceptor complexes.

Searching for Systems with Planar Hexacoordinate Carbons

Here, we present evidence that the D2h M2C50/2+ (M = Li-K, Be-Ca, Al-In, and Zn) species comprises planar hexacoordinate carbon (phC) structures that exhibit four covalent and two electrostatic interactions. These findings have been made possible using evolutionary methods for exploring the potential energy surface (AUTOMATON program) and the Interacting Quantum Atoms (IQA) methodology, which support the observed bonding interactions. It is worth noting, however, that these structures are not the global minimum. Nonetheless, incorporating two cyclopentadienyl anion ligands (Cp) into the CaC52+ system has enhanced the relative stability of the phC isomer. Moreover, cycloparaphenylene ([8]CPP) provides system protection and kinetic stability. These results indicate that using appropriate ligands presents a promising approach for expanding the chemistry of phC species.

Boat and Chair Shaped Hexahalogen Synthons.

Non-covalent halogen bonding interactions are quintessential in crystal engineering for the construction of distinctive supramolecular synthons. Here, we report the first crystalline evidences of unique boat and chair shaped cyclic hexahalogen synthons in the crystal structures of α,α,α',α',4-pentabromo-o-xylene (PBX) and α,α,α',α',4,5-hexabromo-o-xylene (HBX) respectively. Nature and stability of constituent interactions in the supramolecular synthons are scrutinized with the help of quantum-chemical calculations. Pendás' interacting quantum atoms approach confirmed the stability of Br⋅⋅⋅Br interactions leading to boat and chair shaped synthons with major contribution from exchange-correlation. Although both the molecules are achiral in nature, the packing forces guide PBX to crystallize in the chiral space group P21 with a helix-like orientation while HBX packs in a centrosymmetric P21 /n space group. The extended furcations in the pentabromo derivative construct a molecular framework consisting of macrocycles realized through halogen bonding.

Linking the Interatomic Exchange-Correlation Energy to ExperimentalJ-Coupling Constants

The main aim of the current work is to find an experimental connection to the interatomic exchange-correlation energy as defined by the energy decomposition method Interacting Quantum Atoms (IQA). A suitable candidate as (essentially) experimental quantity is the nuclear magnetic resonance (NMR) J-coupling constant denoted 3J(H,H'), which a number of previous studies showed to correlate well with QTAIM's delocalization index (DI), which is essentially a bond order. Inspired by Karplus equations, here, we investigate correlations between 3J(H,H') and a relevant dihedral angle in six simple initial compounds of the shape H3C-YHn (Y = C, N, O, Si, P, and S), N-methylacetamide (as prototype of the peptide bond), and five peptide-capped amino acids (Gly, Ala, Val, Ile, and Leu) because of the protein direction of the force field FFLUX. In conclusion, except for methanol, the inter-hydrogen exchange-correlation energy Vxc(H,H') makes the best contact with experiment, through 3J(H,H'), when multiplied with the internuclear distance RHH'.

Nature and Strength of Weak O⋅⋅⋅O Interactions in Nitryl Halide Dimers.

The use of real space functions and molecular graphs has pushed some chemists to wonder: Are interactions between negatively charged oxygen atoms possible? In this contribution we analyze whether there is a real interaction between oxygen atoms in nitryl halide dimers (XNO2 )2 (X=F, Cl, Br and I) and in tetranitromethane and derivatives. Based on ab-initio and density functional theories (DFT) methods, we show these complexes are weakly stabilized. Energy decomposition analyses based on local molecular orbitals (LMOEDA) and interacting quantum atoms (IQA) reveal both dispersion and exchange play a crucial role in the stabilization of these complexes. Electron charge density and IQA analyses indicate that the oxygen atoms are connected by privileged exchange channels. In addition, electrostatic interactions between O and N atoms are also vital for the stabilization of the complexes. Finally, a reasonable explanation is given for the dynamic behavior of nitryl groups in tetranitromethane and derivatives.

Wave function analyses of scandium-doped aluminium clusters, AlnSc (n = 1-24), and their CO2 fixation abilities.

Nanoclusters represent a connection between (i) solid state systems and (ii) species in the atomic and molecular domains. Additionally, nanoclusters can also have very interesting electronic, optical and magnetic properties. For example, some aluminium clusters behave as superatoms and the doping of these clusters might strengthen their adsorption capabilities. Thus, we address herein the structural, energetic and electronic characterisation of scandium-doped aluminium clusters (AlnSc (n = 1-24)) by means of density functional theory calculations and quantum chemical topology wave function analyses. We studied the effect of Sc-doping on the structure and charge distribution by considering pure Al clusters as well. The quantum theory of atoms in molecules (QTAIM) reveals that interior Al atoms have large negative atomic charges (≈2a.u.) and hence the atoms surrounding them are considerably electron deficient. The Interacting Quantum Atoms (IQA) energy partition allowed us to establish the nature of the interaction between the Al13 superatom and the Al12Sc cluster with Al to form the complexes Al14 and Al13Sc, respectively. We also used the IQA approach to examine (i) the influence of Sc on the geometry of the AlnSc complexes along with (ii) the cooperative effects in the binding of AlnSc and Aln+1 clusters. We also exploited the QTAIM and IQA approaches to study the interaction of the electrophilic surface of the examined systems with CO2. Overall, we observe that the investigated Sc-doped Al complexes with a marked stability towards disproportionation reactions exhibit strong adsorption energies with CO2. Concomitantly, the carbon dioxide molecule is considerably distorted and destabilised, conditions which might prepare it for further chemical reactions. Altogether, this paper gives valuable insights on the tuning of the properties of metallic clusters for their design and exploitation in custom-made materials.

Density functional theory study of crown ether-magnesium complexes: from a solvated ion to an ion trap.

Metal ion detection rests on host-guest recognition. We propose a theoretical protocol for designing an optimal trap for a desired metal cation. A host for magnesium ions was sought for among derivatives of crown ethers 12-crown-4, 15-crown-5, and 18-crown-6. Mg-crown complexes and their hydrated counterparts with water molecules bound to the cation were optimized using density functional theory. Based on specific geometric criteria, Interacting quantum atoms analysis and density functional theory-based molecular dynamics of Mg-crown complexes immersed in water, crown ethers for optimal accommodation of Mg2+ in aqueous solution were identified. Selectivity of the chosen crowns towards Na+, K+, and Ca2+ ions is addressed.

Bonding in the high spin lithium clusters:Non‐nuclearattractors play a crucial role

The bonding in lithium high-spin clusters contradicts the usual chemical bonding concept since there are no electron pairs between the atoms, and they are bound with parallel spin electrons. Quantum theory of atoms in molecules and interacting quantum atom analysis (IQA) were used to investigate the nature of bonding in the high-spin clusters. Our findings demonstrate that the non-nuclear attractors (NNAs) are an essential component of the high-spin lithium clusters and play a key role in keeping them stable. Based on IQA energy terms, an electrostatic destabilizing interaction between the lithium atoms works against the cluster formation. On the other hand, the interactions between lithium atoms and NNA basins are stabilizing and outweigh the lithium-lithium destabilizing effects. In fact, NNAs tend to draw lithium atoms together and stabilize the resulting cluster. The high-spin clusters of lithium can be regarded as electrostatically driven compounds since the electrostatic components are primarily responsible for the stabilizing interactions between NNAs and Li atoms. The only exception is 3 Li2 , which lacks NNA and has a non-repellent lithium-lithium interaction. Indeed, in the 3 Li2 , the interatomic electrostatic component is negligibly small, and the exchange-correlation term leads to a weak bonding interaction.

Electron Density Analysis of Metal–Metal Bonding in a Ni4 Cluster Featuring Ferromagnetic Exchange

We present a combined experimental and theoretical study of the nature of the proposed metal-metal bonding in the tetranuclear cluster Ni4(NPtBu3)4, which features four nickel(I) centers engaged in strong ferromagnetic coupling. High-resolution single-crystal synchrotron X-ray diffraction data collected at 25 K provide an accurate geometrical structure and a multipole model electron density description. Topological analysis of the electron density in the Ni4N4 core using the quantum theory of atoms in molecules clearly identifies the bonding as an eight-membered ring of type [Ni-N-]4 without direct Ni-Ni bonding, and this result is generally corroborated by an analysis of the energy density distribution. In contrast, the calculated bond delocalization index of ∼0.6 between neighboring Ni atoms is larger than what has been found for other bridged metal-metal bonds and implies direct Ni-Ni bonding. Similar support for the presence of direct Ni-Ni bonding is found in the interacting quantum atom approach, an energy decomposition scheme, which suggests the presence of stabilizing Ni-Ni bonding interactions with an exchange-correlation energy contribution approximately 50% of that of the Ni-N interactions. Altogether, while the direct interactions between neighboring Ni centers are too weak and sterically constrained to bear the signature of a topological bond critical point, other continuous measures clearly indicate significant Ni-Ni bonding. These metal-metal bonding interactions likely mediate direct ferromagnetic exchange, giving rise to the high-spin ground state of the molecule.

Binding Energy Partition of Promising IRAK‐4 Inhibitor (Zimlovisertib) for the Treatment of COVID‐19 Pneumonia

The front cover artwork is provided by César A. Zapata-Acevedo and co-workers at the Institute of Chemistry of the National Autonomous University of Mexico, the IMDEA Materials Institute, the University of Manchester and Tecnológico de Monterrey Campus Santa Fe. The image shows the fragment-based drug design process for candidate Zimlovisertib. The Interacting Quantum Atoms method reveals the adequacy (or lack of) of the chemical changes throughout the design of this IRAK4 inhibitor. Read the full text of the Research Article at 10.1002/cphc.202200455.

Energetic Origins of Force Constants: Adding a New Dimension to the Hessian Matrix via Interacting Quantum Atoms.

The Interacting Quantum Atoms (IQA) energy decomposition scheme divides the total energy of a molecule into intra- and interatomic contributions. While the former relates to the kinetic and potential energies of electrons inside a unique individual atomic basin, the latter contains the Coulomb and exchange-correlation potentials between electrons from two atomic basins. Considering that the molecular energy is a sum of IQA contributions, the Hessian matrix can also be written as a sum of "IQA Hessian" matrices, whose elements are second derivatives of IQA terms. Herein, we present a mathematical formalism for the IQA decomposition of force constants revealing their energetic origins. The method consists of adding a new dimension to the Hessian matrix, which becomes 3N × 3N × N2, with N being the number of atoms in the molecule and N2 the number of IQA terms. Since there is no analytical method that produces the IQA second derivatives, the three-dimensional IQA Hessian is numerically calculated. When studying molecular vibrations, force constants, providing information about the nature of chemical bond and related to infrared frequencies, can be obtained by Wilson's FG method, which involves detailed manipulations of the Hessian matrix. In this paper, the methodology is reported and validated for a set of 30 molecules and more than 200 force constants and their interactions. Energetic origins of force constants are presented for diatomics and small molecules containing carbon-carbon, oxygen-oxygen, and carbon-oxygen bonds with different bond orders. It is found that bond stability and stiffness can have strikingly different energetic origins.

Binding Energy Partition of Promising IRAK-4 Inhibitor (Zimlovisertib) for the Treatment of COVID-19 Pneumonia.

The technique of Fragment‐Based Drug Design (FBDD) considers the interactions of different moieties of molecules with biological targets for the rational construction of potential drugs. One basic assumption of FBDD is that the different functional groups of a ligand interact with a biological target in an approximately additive, that is, independent manner. We investigated the interactions of different fragments of ligands and Interleukin‐1 Receptor‐Associated Kinase 4 (IRAK‐4) throughout the FBDD design of Zimlovisertib, a promising anti‐inflammatory, currently in trials to be used for the treatment of COVID‐19 pneumonia. We utilised state‐of‐the‐art methods of wave function analyses mainly the Interacting Quantum Atoms (IQA) energy partition for this purpose. By means of IQA, we assessed the suitability of every change to the ligand in the five stages of FBDD which led to Zimlovisertib on a quantitative basis. We determined the energetics of the interaction of different functional groups in the ligands with the IRAK‐4 protein target and thereby demonstrated the adequacy (or lack thereof) of the changes made across the design of this drug. This analysis permits to verify whether a given alteration of a prospective drug leads to the intended tuning of non‐covalent interactions with its protein objective. Overall, we expect that the methods exploited in this paper will prove valuable in the understanding and control of chemical modifications across FBDD processes.

The IQA Energy Partition in a Drug Design Setting: A Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B) Case Study.

The interaction of the thumb site II of the NS5B protein of hepatitis C virus and a pair of drug candidates was studied using a topological energy decomposition method called interacting quantum atoms (IQA). The atomic energies were then processed by the relative energy gradient (REG) method, which extracts chemical insight by computation based on minimal assumptions. REG reveals the most important IQA energy contributions, by atom and energy type (electrostatics, sterics, and exchange–correlation), that are responsible for the behaviour of the whole system, systematically from a short-range ligand–pocket interaction until a distance of approximately 22 Å. The degree of covalency in various key interatomic interactions can be quantified. No exchange–correlation contribution is responsible for the changes in the energy profile of both pocket–ligand systems investigated in the ligand–pocket distances equal to or greater than that of the global minimum. Regarding the hydrogen bonds in the system, a “neighbour effect” was observed thanks to the REG method, which states that a carbon atom would rather not have its covalent neighbour oxygen form a hydrogen bond. The combination of IQA and REG enables the automatic identification of the pharmacophore in the ligands. The coarser Interacting Quantum Fragments (IQF) enables the determination of which amino acids of the pocket contribute most to the binding and the type of energy of said binding. This work is an example of the contribution topological energy decomposition methods can make to fragment-based drug design.

A QCT View of the Interplay between Hydrogen Bonds and Aromaticity in Small CHON Derivatives.

The somewhat elusive concept of aromaticity plays an undeniable role in the chemical narrative, often being considered the principal cause of the unusual properties and stability exhibited by certain skeletons. More recently, the concept of aromaticity has also been utilised to explain the modulation of the strength of non-covalent interactions (NCIs), such as hydrogen bonding (HB), paving the way towards the in silico prediction and design of tailor-made interacting systems. In this work, we try to shed light on this area by exploiting real space techniques, such as the Quantum Theory of Atoms in Molecules (QTAIM), the Interacting Quantum Atoms (IQA) approaches along with the electron delocalisation indicators Aromatic Fluctuation (FLU) and Multicenter (MCI) indices. The QTAIM and IQA methods have been proven capable of providing an unbiased and rigorous picture of NCIs in a wide variety of scenarios, whereas the FLU and MCI descriptors have been successfully exploited in the study of diverse aromatic and antiaromatic systems. We used a collection of simple archetypal examples of aromatic, non-aromatic and antiaromatic moieties within organic molecules to examine the changes in delocalisation and aromaticity induced by the Aromaticity and Antiaromaticity Modulated Hydrogen Bonds (AMHB). We observed fundamental differences in the behaviour of systems containing the HB acceptor within and outside the ring, e.g., a destabilisation of the rings in the former as opposed to a stabilisation of the latter upon the formation of the corresponding molecular clusters. The results of this work provide a physically sound basis to rationalise the strengthening and weakening of AMHBs with respect to suitable non-cyclic non-aromatic references. We also found significant differences in the chemical bonding scenarios of aromatic and antiaromatic systems in the formation of AMHB. Altogether, our investigation provide novel, valuable insights about the complex mutual influence between hydrogen bonds and systems.