Resonance-assisted Hydrogen Bond Research Articles

Investigation of resonance assisted hydrogen bond (RAHB) in some pyridine-based complexes: Intramolecular and intermolecular interactions

Intra- and intermolecular hydrogen bonding interactions in some pyridine-based complexes that have R groups without (H, –C2H5, and –C4H9) and with (−C2H3, –C4H5, –C6H7, and –C8H9) π-conjugated system were investigated using quantum mechanical calculations to know role of resonance on strength of interactions. Geometrical parameters and electronic properties based on atoms in molecules (AIM) analysis were studied to interpret the interactions. Also, aromaticity of the rings of the complexes was evaluated using aromatic fluctuation index (FLU) and para-delocalization index (PDI) to connect the mentioned benchmark to energy of the hydrogen bond interactions. Indeed, localized molecular orbital energy decomposition analysis (LMO-EDA) was employed to realize contribution of components of energy in stability of the complexes.

Tuning the Strength of the Resonance-Assisted Hydrogen Bond in Acenes and Phenacenes with Two o-Hydroxyaldehyde Groups-The Importance of Topology.

The fact that intramolecular resonance-assisted hydrogen bonds (RAHBs) are stronger than conventional ones is attributed to the partial delocalization of the π-electrons within the hydrogen bond (HB) motif, the so-called quasi-ring. If an aromatic ring is involved in the formation of the RAHB, previous studies have shown that there is an interplay between aromaticity and HB strength. Moreover, in 1,3-dihydroxyaryl-2-aldehydes, some of us found that the position of the quasi-ring formed by the substituents interacting through RAHB influences the strength of the H bonding, the HBs being stronger when a kinked-like structure is generated by formation of the quasi-ring. In this work, we explore this concept further by considering a set of acenes and phenacenes of different sizes with two o-hydroxyaldehyde substituents. Calculations with the CAM-B3LYP/6-311++G(d,p) + GD3B method show that for long acenes or phenacenes, once the substituent effect loses importance because quasi-rings are pulled apart far from each other, the different topologies rule the HB distances. This fact can be explained in most cases using an extended Clar's aromatic π-sextet model. In some kinked systems, however, the justification from the Clar model has to be complemented by taking into account the repulsion between hydrogen atoms. Triphenylene-like compounds with different numbers of benzene rings have been studied, finding out a very good relationship between aromaticity of the ipso- and quasi-rings with the RAHB distances. This result confirms the importance of the communication of the π-systems of the ipso- and quasi-rings.

How Resonance Modulates Multiple Hydrogen Bonding in Self-Assembled Systems.

The secondary electrostatic interaction (SEI) has been regarded as the fundamental cause for the relative strengths of multiple hydrogen bonds for decades, though recent studies challenged its validation. Here, we used our developed block-localized wave function (BLW) method, which is a variant of ab initio valence bond (VB) theory and can self-consistently derive the wave function for a strictly electron-localized state, to study a series of exemplary multiply hydrogen-bonded complexes and critically examine the role of SEI in the binding. Our computations show that the multiple hydrogen bond in self-assembled complexes is a kind of resonance-assisted hydrogen bond (RAHB) in nature, and the π resonance which moves electron density from the hydrogen bond donor to the acceptor is the true origin of the different hydrogen bond strengths. By quenching the π resonance effect, the hydrogen bond strengths become nearly identical for various neutral doubly, triply, and quadruply hydrogen-bonded dimers where in general the SEI model works. In other words, the SEI plays only a minor role in multiply hydrogen-bonded complexes, and the π resonance, which changes not only electron densities but also molecular polarities (dipole moments), is the major force.

A Comprehensive Theoretical Study of Amide Resonance, Intramolecular Hydrogen Bonding, and π-Electron Delocalization in Diformyl and Dithioformyl Amine

In the present work, a comprehensive theoretical study of diformyl (DFA) and dithioformylamine (DTFA) were performed by various theoretical methods, HF, B3LYP, and MP2 with 6‑311++G(3df,3pd) basis set, and the equilibrium conformations were determined. According to these calculations, tautomeric and conformeric preferences, intramolecular hydrogen bond (IMHB) and π-electron delocalization were investigated. Generally, DAI/DTAI tautomers have extra stability with respect to the AI/TAI ones. Also, among the AI/TAI series, the AI-11/TAI-13 conformer with/without IMHB is the most stable tautomer. Moreover, our computation results reveal that the formation of the intramolecular hydrogen bond is accepted as the origin of conformational preferences. The results of hydrogen bond descriptors, such as HB energy, geometrical, topological, spectroscopic and molecular orbital parameters are in agreement with the related energy values and show that the strength of intramolecular hydrogen bond in DFA is more than DTFA ones. On the other hands, π-electron delocalization of chelated rings was measured using various indices, such as q, λ', λ, and HOMA index. Finally, the orders of hydrogen bond strength and π-electron delocalization, obtained by some of the indices, support the resonance assisted hydrogen bond theory.

On the performance of molecular tailoring approach for estimation of the intramolecular hydrogen bond energies of RAHB systems: a comparative study

In the current research, the performance of molecular tailoring approach (MTA) for estimation of the intramolecular hydrogen bond (IMHB) energies of the simple resonance-assisted hydrogen bond (RAHB) systems was theoretically investigated. First, a wide range of malonaldehyde derivatives (36 members) including the F, Cl, Br, CN, NO2, ethen (-CH=CH2), ethin (-C ≡ CH), CF3, OCH3, C2H5, CH3, and Ph substitutions at R1, R2, and R3 positions were considered. Then, all of these molecules at MP2/6-311++G(d, p) level of theory have been optimized and their MTA energies were calculated. Furthermore, various qualitative descriptors of IMHB such as structural, spectroscopic, topological, and molecular orbital parameters were considered, and all of correlations between these factors and MTA energies were explored. According to their regression coefficients (R2), the linear characteristic of correlations obeys the following order:$$ {H}_{\mathrm{H}\dots \mathrm{O}}>{d}_{\mathrm{O}-\mathrm{H}}>{E}_{\mathrm{CT}}>{V}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{\rho}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{\nu}_{\mathrm{O}-\mathrm{H}}>{d}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{d}_{\mathrm{O}\bullet \bullet \bullet \mathrm{O}} $$$$ 0.952\kern1.5em 0.940\kern1.2em 0.936\kern0.75em 0.914\kern1.2em 0.901\kern1.2em 0.834\kern1em 0.789\kern1.3em 0.755 $$ These correlation coefficients have compared with the corresponding R2 values of other models such as RRM, RBM, GCM, IRM, and OCM, which leads to the following order of linearity:$$ \mathrm{MTA}\ge \mathrm{RRM}>\mathrm{RBM}>\mathrm{GCM}>\mathrm{IRM}>\mathrm{OCM}. $$ Finally, the significance of π-electron delocalization (π-ED) of RAHB rings is also evaluated by the geometrical factor of Gilli (λ) and the harmonic oscillator model of aromaticity (HOMA) that presents the excellent linear correlations with MTA energies, which may be implied on the validity of RAHB theory.

QTAIM, NBO, and NMR studies of hydrogen bonds in capecitabine

Intramolecular and Intermolecular hydrogen bonds of capecitabine, a pharmaceutically active substance in the group of fluorinated cytosines, have been investigated by density functional calculations at B3LYP level of theory using some Pople-style basis sets augmented with polarized and diffuse functions. To perform the calculations, one molecule (CAP-M) and three molecules (CAP-T) of capecitabine are modeled by available X-ray crystal analysis in the literature. The topological parameters of the electron density distributions have been analyzed in terms of the quantum theory of atoms in molecules (QTAIM). The calculated hydrogen bond energies, together with the structural parameters, confirm two intramolecular hydrogen bonds, and only one intermolecular hydrogen bond in the trimer or cluster. Calculated ring critical points approve the resonance-assisted hydrogen bonds in the intramolecular hydrogen bonds. Moreover, the natural bond orbital analysis (NBO) has been used to evaluate the nature of hydrogen bonding interactions and charge analysis. The calculated 1H NMR and 17O NMR chemical shifts (CS) are significantly influenced by forming the hydrogen bond bridges. CS values are in excellent agreement with the structural parameters, QTAIM, and NBO results. Molecular electrostatic potential maps confirm the regions of hydrogen bonds donor and hydrogen bonds acceptor of the title molecule.

About the Aromaticity of symm-Triaminotrinitrobenzene.

Aromaticity and structural features of the isolated symm-triaminotrinitrobenzene (TATB) were examined using the nonempirical ab initio quantum chemical method and molecular dynamics at the Car-Parrinello level. Different criteria of the aromaticity were combined with the study of conformational flexibility of molecule and analysis of the electron density distribution. It was found that the cooperative effect of the resonance-assisted hydrogen bonds results in the ultimate decreasing aromaticity of the benzene ring in TATB. Values of the HOMA index indicate that it could be classified as low-aromatic in equilibrium state at zero temperature but completely nonaromatic at room temperature. An extremely high flexibility of the molecule is also not typical for aromatic rings. The electron delocalization in H-bonded O═N-C═C-N-H quasi-aromatic rings was found to be greater than that in the benzene ring of TATB.

Assessing Parameter Suitability for the Strength Evaluation of Intramolecular Resonance Assisted Hydrogen Bonding in o-Carbonyl Hydroquinones.

Intramolecular hydrogen bond (IMHB) interactions have attracted considerable attention due to their central role in molecular structure, chemical reactivity, and interactions of biologically active molecules. Precise correlations of the strength of IMHB’s with experimental parameters are a key goal in order to model compounds for drug discovery. In this work, we carry out an experimental (NMR) and theoretical (DFT) study of the IMHB in a series of structurally similar o-carbonyl hydroquinones. Geometrical parameters, as well as Natural Bond Orbital (NBO) and Quantum Theory of Atoms in Molecules (QTAIM) parameters for IMHB were compared with experimental NMR data. Three DFT functionals were employed to calculated theoretical parameters: B3LYP, M06-2X, and ωB97XD. O…H distance is the most suitable geometrical parameter to distinguish among similar IMHBs. Second order stabilization energies ΔEij(2) from NBO analysis and hydrogen bond energy (EHB) obtained from QTAIM analysis also properly distinguishes the order in strength of the studied IMHB. ΔEij(2) from NBO give values for the IMHB below 30 kcal/mol, while EHB from QTAIM analysis give values above 30 kcal/mol. In all cases, the calculated parameters using ωB97XD give the best correlations with experimental 1H-NMR chemical shifts for the IMHB, with R2 values around 0.89. Although the results show that these parameters correctly reflect the strength of the IMHB, when the weakest one is removed from the analysis, arguing experimental considerations, correlations improve significantly to values around 0.95 for R2.

Improving the mesomorphic behaviour of supramolecular liquid crystals by resonance-assisted hydrogen bonding

A significant impact of resonance-assisted hydrogen-bonding (RAHB) on the liquid crystalline behavior of hydrogen-bonded mesogens is reported and systematically investigated.

Investigations of the hydrogen bond in the crystals of tropolone and thiotropolone via car-parrinello and path integral molecular dynamics.

Car-Parrinello and path integrals molecular dynamics (CPMD and PIMD) simulations were carried out for the 10π-electron aromatic systems: 2-hydroxy-2,4,6-cycloheptatrien-1-one, commonly known as Tropolone (I) and 2-hydroxy-2,4,6-cycloheptatriene-1-thione, called Thiotropolone (II) in vacuo and in the solid state. The extremely fast proton transfer (FPT) and "prototropy" tautomerism in the keto-enol (thione-enethiol) systems have been analyzed on the basis of CPMD and PIMD methods level. Comparisons of two-dimensional (2D) free-energy landscapes of reaction coordinate δ-parameter and RO…O or RO…S distances shows that the OH… tautomer to be more favorable in the Thiotropolone. The hydrogen between the oxygen and the sulfur atoms adopts a starkly asymmetrical position in the double potential well. The values of the energy barriers for the FPT were calculated and suggested a strong hydrogen bond with low barrier for FPT mechanism. These studies and the 2D average index of π-delocalization 〈λ〉 landscape of time evolutions of RO1…O2 and RC7O2 or RC7S1 distances for the both crystals indicate that hydrogen bonds in the crystals of Tropolone (I) and Thiotropolone (II) have characteristic properties for the type of bonding model resonance-assisted hydrogen bonds and also low-barrier hydrogen bonds. In the crystal of the Thiotropolone (II), we found the hydrogen bond OH…S existing without the equilibrium of the two tautomers whereas in the crystal of the Tropolone (I) has been confirmed the hydrogen bond OH…O existing with the equilibrium of the two tautomers. It was also found the significant differences in frequency, speed, and the image of the FPT in the studied crystals. © 2018 Wiley Periodicals, Inc.

Solvent effects on the molecular stability, intramolecular hydrogen bond, and π-electron delocalization in the simple RAHB systems with different donors and acceptors: a quantum chemical study

In the present study, solvent effects on the molecular stability, intramolecular hydrogen bond (IMHB), and π-electron delocalization (π-ED) in some of the simple resonance-assisted hydrogen bond (RAHB) systems with different donors and acceptors are investigated. In this regard, all of the H-bonded structures (enol, thiol, and selenol) in the gas phase and presence of water/DMSO solvents with polarizable continuum (PCM)/self-consistent isodensity PCM methods at the M06-2X/6-311G++(d,p) level of theory are optimized. Relative energies clearly indicate that the enol conformers are more stable than the thiol and selenol ones in the gas phase while in the presence of polar solvents, the thiol structures are more stable than the other members. In the RAHB systems, the IMHB, π-ED, and tautomerization process are important factors in determining the stability of the H-bonded conformers. A survey of tautomeric equilibriums clearly shows that the tautomerization/activation energy of thio ⇋ thiol equilibrium is greater/smaller than the other equilibriums. These results reveal that the thiol tautomer is more preferred than the enol and selenol ones, from kinetic and thermodynamic points of view. Estimation of the IMHB by different descriptors emphasizes the presence of a stronger IMHB in the enol conformers. Moreover, the π-ED of enol tautomers are greater than those of the thiol and selenol ones. The results of IMHB and π-ED descriptors are compatible/incompatible with the stability order of the gas phase/solvents. Consequently, one can conclude that in the gas phase, the IMHB and π-ED are superior factors to determine the stability of tautomers. But in the presence of polar solvents, the tautomerization process is a dominant factor.

A Quantum Chemical Study of Various Intramolecular Hydrogen Bonds in 4-Amino-3-Pentene-2-Thial

B3LYP and MP2 methods with the most popular basis set, 6-311++G(d,p) are applied to optimize the equilibrium conformers of 4-amino-3-pentene-2-thial. Furthermore, to have more reliable energies, the total electron energies of all forms are recomputed at the CBS-4M level of theory. A theoretical investigation of the equilibrium conformers clearly shows that various intramolecular hydrogen bonds (IHBs) such as N–H...S, S–H...N, S–H...π, C–H...N, and C–H...S are the most effective factors in the conformational preference of thialamine, thiolimine, and thialimine groups. Hence, the IHB strengths are evaluated in various resonance-assisted hydrogen bond systems by geometrical factors, topological parameters, and charge transfers corresponding to orbital interactions. Also, the solvent effect on the IHB strength is considered using Tomasi′s PCM. Our results in the gas phase reveal that the thialamine group has extra stability with respect to thiolimine and thialimine ones. The population analyses of all the possible conformers by the NBO method predict that the origin of this tautomeric preference is mainly due to more significant π electron delocalization in the framework of thialamine forms, especially πC=C → π C = S* and Lp(N) → π C = C* charge transfers. Moreover, the excited state properties of IHBs in these systems are investigated theoretically using the time-dependent DFT method.

A resonance-assisted intra-molecular hydrogen bond in compounds containing 2-hy-droxy-3,5-di-nitro-benzoic acid and its various deprotonated forms: redetermination of several related structures.

A large number of structural determinations of compounds containing 2-hy-droxy-3,5-di-nitro-benzoic acid (I) and its various deprotonated forms, 2-hy-droxy-3,5-di-nitro-benzoate (II) or 2-carb-oxy-4,6-di-nitro-phenolate (III), are biased. The reason for the bias follows from incorrectly applied constraints or restraints on the bridging hydrogen, which is involved in the intra-molecular hydrogen bond between the neighbouring carb-oxy-lic/carboxyl-ate and oxo/hy-droxy groups. This hydrogen bond belongs to the category of resonance-assisted hydrogen bonds. The present article suggests corrections for the following structure determinations that have been published in Acta Crystallographica: DUJZAK, JEVNAA, LUDFUL, NUQVEB, QIQJAD, SAFGUD, SEDKET, TIYZIM, TUJPEV, VABZIJ, WADXOR, YAXPOE [refcodes are taken from the Cambridge Structural Database [CSD; Groom et al. (2016 ▸). Acta Cryst. B72, 171-179]. The structural features of the title mol-ecules in all the retrieved structures, together with structures that contain 3,5-di-nitro-2-oxidobenzoate (IV), are discussed. Attention is paid to the localization of the above-mentioned bridging hydrogen, which can be situated closer to the O atom of the carboxyl-ate/carb-oxy-lic group or that of the hy-droxy/oxo group. In some cases, it is disordered between the two O atoms. The position of the bridging hydrogen seems to be dependent on the pKa (base) although with exceptions. A stronger basicity enhances the probability of the presence of a phenolate (III). The present article examines the problem of the refinement of such a bridging hydrogen as well as that of the hydrogen atoms involved in the hy-droxy and primary and secondary amine groups. It appears that the best model, in many cases, is obtained by fixing the hydrogen-atom position found in the difference electron-density map while refining its isotropic displacement parameter.

Synthesis of 3-Methylidene-1-tosyl-2,3-dihydroquinolin-4(1H)-ones as Potent Cytotoxic Agents.

An efficient synthetic strategy to 3-methylidene-2,3-dihydroquinolin-4(1H)-ones variously substituted in position 2 has been developed. The title compounds were synthesized in the reaction sequence involving reaction of diethyl methylphosphonate with methyl 2-(tosylamino)benzoate, condensation of thus formed diethyl 2-oxo-2-(2-N-tosylphenyl)ethylphosphonate with various aldehydes followed by successful application of the obtained 3-(diethoxyphosphoryl)-1,2-dihydroquinolin-4-ols as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde. Also, enantioselective approach to the target compounds has been evaluated using 3-dimenthoxyphosphoryl group as a chiral auxiliary. Single X-ray crystal analysis of (2S)-3-(dimenthoxyphosphoryl)-2-phenyl-1-tosyldihydroquinolin-4-ol revealed the presence of strong resonance-assisted hydrogen bond (RAHB). The obtained 3-methylidene-2,3-dihydroquinolin-4(1H)-ones were then tested for their cytotoxic activity against two leukemia cell lines NALM-6 and HL-60 and a breast cancer MCF-7 cell line. All compounds showed very high cytotoxic activity with the IC50 values mostly below 1μm in all three cancer cell lines. The selected analogs were also tested on human umbilical vein endothelial cells (HUVEC) and on human mammary gland/breast cells (MCF-10A) to evaluate their influence on normal cells. Since one of the most serious problems in cancer chemotherapy is the development of drug resistance, the mRNA levels and activity of ABCB1 transporter considered to be the most important factor engaged in drug resistance, were evaluated in MCF-7 cells treated with two selected analogs. Both compounds were strong ABCB1 transporter inhibitors that could prevent efflux of anticancer drugs from cancer cells.

Car–Parrinello and Path Integral Molecular Dynamics Study of the Proton Transfer in the Intramolecular Hydrogen Bonds in the Ketohydrazone–Azoenol System

Car-Parrinello (CPMD) and path integral molecular dynamics (PIMD) simulations were carried out for 1-(phenylazo)-2-naphthol (I) and 1-(4-F-phenylazo)-2-naphthol (II) (Sudan I) in vacuo and in the solid state at 298 K. The fast proton transfer (FPT) and tautomerism in the ketohydrazone-azoenol systems have been analyzed on the basis of CPMD and PIMD methods level. The two-dimensional free-energy landscape of reaction coordinate δ-parameter and RN···O distances shows the NH tautomer to be more favorable in the gas phase as well as in the solid state according to the CP and PI results, respectively. The hydrogen between the nitrogen and the oxygen atoms adopts a starkly asymmetrical position in the double potential well. The molecular geometry and energy barrier for the intramolecular proton transference were calculated, and the value found suggested a strong hydrogen bond with low barrier for FPT mechanism. These studies and the two-dimensional average index of π-delocalization ⟨λ⟩ landscape of time evolutions of RN1···O1 and RC1═O1 distances for both the crystals indicate that the hydrogen bonds in the crystals of 1-(phenylazo)-2-naphthol (I) and 1-(4-F-phenylazo)-2-naphthol (II) have characteristic properties for the type of bonding model: resonance-assisted hydrogen bonds and low-barrier hydrogen bonds, without the existence of equilibrium in the two tautomers. The infrared spectrum has been calculated, and a comparative vibrational analysis has been performed. The CPMD vibrational results appear to qualitatively agree with the experimental ones.

Open-Resonance-Assisted Hydrogen Bonds and Competing Quasiaromaticity.

The delocalization of electron density upon tautomerization of a proton across a conjugated bridge can alter the strength of hydrogen bonds. This effect has been dubbed resonance-assisted hydrogen bonding (RAHB) and plays a major role in the energetics of the tautomeric equilibrium. The goal of this work was to investigate the role that π-delocalization plays in the stability of RAHBs by engaging other isomerization processes. Similarly, acid-base chemistry has received little experimental attention in studies of RAHB, and we address the role that acid-base effects play in the tautomeric equilibrium. We find that π-delocalization and the disruption of adjacent aromatic rings is the dominant effect in determining the stability of a RAHB.

Enantioselective Liquid–Liquid Extraction of Underivatized Amino Acids with Simple Chiral Aminophenyl‐Aldehyde

The derivative of aminophenyl‐aldehyde with an asymmetric carbon and an uryl group, (S)‐2, was synthesized. The combination of (S)‐2 and aliquat‐336 in CDCl3 extracted underivatized amino acids in water layer by imine formation with enantioselectivities of 12/1 for Phe, 13/1 for Val, and 12/1 for Leu, which are comparable with those of previously reported binaphthol‐based extractor (S)‐1. The enantioselectivities of (S)‐2 is remarkable considering the low molecular weight compared to (S)‐1. Density functional theory computations and experimental data demonstrate that imine bond is strengthened by resonance‐assisted hydrogen bond with the nearby NH group.

Doxycycline hydrate and doxycycline hydrochloride dihydrate – crystal structure and charge density analysis

Abstract High-resolution low-temperature X-ray diffraction experiments for doxycycline monohydrate and hydrochloride dihydrate have been performed. Translation-Libration-Screw (TLS) analysis for both crystal forms as well as the data from neutron diffraction experiment for hydrochloride combined with the Hansen-Coppens formalism resulted in precise charge density distribution models for both the zwitterionic monohydrate and a protonated hydrochloride crystal forms. Their detailed topological analysis suggested that the electron structure of doxycycline’s amide moiety undergoes significant changes during protonation due to formation of a very strong resonance-assisted hydrogen bond. A notably increased participation of amide nitrogen atom and hydrogen-accepting oxygen atom in the resonance upon doxycycline protonation was observed. A comparison of TLS- and neutron data-derived hydrogen parameters confirmed the experimental neutron data to be vital for proper description of intra- and inter-molecular interactions in this compound. Finally, calculated lattice and interaction energies quantified repulsive Dox-Dox interactions in the protonated crystal form of the antibiotic, relating with a good solubility of doxycycline hydrochloride relative to its hydrate.

Anion˗π and Intramolecular Hydrogen Bond Interactions in the Various Complexes of 1,3,5-Triamino-2,4,6-trinitrobenzene with H-, F-, Cl- and Br- Anions

The quantum chemical calculations were performed to investigate the interplay between the anion˗π and intramolecular hydrogen bond (IMHB) interactions in the various complexes of 1,3,5-triamino-2,4,6-trinitrobenzene (ANB) with Hˉ, Fˉ, Clˉ and Brˉ anions. For better understanding the cooperative effects, the parent molecules (ANB) and the corresponding complexes of 1,3,5˗trinitrobenzene with the mentioned anions are also considered, as a set of the reference points. In this regard, the IMHB and anion˗π interactions are comprehensively analyzed by energetic, geometrical, spectroscopic and topological descriptors. It was found that the coexistence of the anion˗π and IMHB increases the strength of both interactions. Furthermore, the influences of the anion-π and IMHB interactions on the significance of the π˗electron delocalization (π˗ED) of the resonance assisted hydrogen bond (RAHB) units and the aromaticity of the benzene ring are evaluated by the harmonic oscillator model of aromaticity (HOMA), as a geometry based index. According to the HOMA values, we concluded that the coexistence of the mentioned interactions decreases the aromaticity of benzene ring and increases the π˗ED of RAHB units. Finally, the strength of the non-covalent interactions and the significance of π˗ED and aromaticity strongly depend on type of the anion.

A novel potential anticancer chalcone: Synthesis, crystal structure and cytotoxic assay

Recently, a wide number of bioactivities has been discovered for chalcones. These applications depend on structural features such as planarity, electronic delocalization paths and substitution pattern on aromatic rings. This work aimed the structural analysis of a novel nitroaminochalcone (C15H12N2O3, NAC) through single crystal X-ray diffraction technique and assessment of its cytotoxicity against tumor cells. NAC is almost completely planar, as evidenced by the low angle formed between its phenyl rings [4.40 (12)°], which enables the π-electron delocalization through whole molecule. A resonance-assisted hydrogen bond (RAHB) is another interesting intramolecular feature of NAC, which is assembled between the amino and carbonyl groups into a cyclic S (6) motif. The crystal packing is featured by the formation of dimers stabilized by a R22 (16) motif engaging the carbonyl group and nitrobenzene. These dimers are organized in a 2D layer onto (010) through CH⋯O interactions involving the nitro e amine groups in a C12(13)[R12(4)] motif. Furthermore, Hirshfeld surface analysis showed the crystal packing of NAC is also stabilized by both CH⋯π and π⋯π interactions. The compound showed high cytotoxicity against human tumor cells.