Conformational analysis of a secondary hydroxamic acid in aqueous solution by NOE spectroscopy

Hydroxamic acids are metal‐binding compounds used by micro‐organisms and possess applications in medicine and industry. Hydroxamic acids favor two conformations, E and Z; metal binding is limited to the Z conformation. The Z conformation may be identifiable by NOE spectroscopy, but analysis is complicated by the potential for long‐range coupling as well as for relayed NOEs due to conformational switching. In this report, we re‐examine the reported conformational preference of N‐methyl acetohydroxamic acid (NMHA) in D₂O using NOE spectroscopy. We find that the favored conformation of NMHA in aqueous solution is the E conformation, contrary to an earlier report. NOE build‐up curves are proposed as a valuable tool to probe conformational behavior in similar systems. Copyright © 2013 John Wiley & Sons, Ltd.     

1H NMR utilization of through-space effects. II—conformation of dienic ketones

The configurational and conformational assignments of the carbonyl group in the Z- and E-1-(3-substituted-5,5-dimethyl-2-cyclohexen-1-ylidene)-2-butanones are carried out using only the through-space effects of the carbonyl group. It is demonstrated that, regardless of the Z- or E-configuration or the nature of the substituent in position 3, the conformation of the carbonyl group is always s-cis.     

Theoretical investigation of the formic acid decomposition kinetics

Decomposition of formic acid (HCO₂H) proceeds via three unimolecular channels: dehydration, decarboxylation, and dissociation, the latter expected to be of minor contribution to the overall kinetics. In addition, despite the similar values reported for the individual activation energies for the dehydration and decarboxylation reactions, experimental works have shown that the former is dominant in the reaction mechanism. These reactions show pressure-dependent rate coefficients, and the high-pressure condition is not yet verified at atmospheric pressure. This work aims to investigate the influence of temperature and pressure on the rate coefficients. Hence, theoretical calculations at the CCSD(T)/CBS level have been performed to accurately describe the unimolecular reaction and Rice-Ramsperger-Kassel-Marcus (RRKM) rate coefficients have been calculated and integrated for the prediction of k(T,P) rate coefficients, adopting both strong and weak collision models, over the intervals 0.5-10 atm and 298-2200 K. Our results suggest that the isomerization path is important and explains the preference for the (CO + H₂O) channel. Rate coefficients for the (CO₂ + H₂) and (CO + H₂O) formations are given, in s⁻¹, as exp(−34404/T) and exp(−33785/T), respectively. The dissociation limit of 107.29 kcal mol^–1, with respect the Z-HCO₂H conformer, leading to OH + HCO, via a barrierless potential curve, with rate coefficients, in s⁻¹, expressed as k_HCO+OH(T) = 1.68 × 10¹⁷ exp(−56018/T). Temperature and pressure dependence for the HCO + OH → CO₂ + H₂ and HCO + OH → CO + H₂O reactions have also been estimated.     

Solution equilibria of aromatic dinitroso compounds: a combined NMR and DFT study

Solution-state nitroso monomer-azodioxide equilibria and conformational freedom of several aromatic dinitroso derivatives, differing in the spacer group between the aromatic rings, were studied by one- and two-dimensional variable temperature ¹H NMR spectroscopy and by quantum chemical calculations. The proton signals of nitroso monomer-azodioxide mixtures revealed by low-temperature NMR were assigned and validated using B3LYP-D3/6-311+G(2d,p)/SMD level of theory. In almost all cases, a preference towards the formation of only one azodioxy isomer of aromatic dinitroso compounds was found, which was assigned to Z-dimer according to computational data. Nevertheless, the computed small energy difference between the Z- and E-isomer could not account for the extreme preference for Z-dimer formation, indicating an influence of entropic or solvent effects. The formation of shorter oligomers in solution was excluded based on integrated ¹H NMR signal intensities. The experimental results indicated an average dimerization Gibbs energy of about ??5 kJ/mol at 223 K and were found to be in very good correlation with dimerization energies obtained by solution-phase optimization.

     

Effect of Solvents on the Spectra of Some β-Diketones

Acetoacetanilide, benzoylacetanilide and their derivatives have been examined in ultraviolet region in a series of solvents covering a broad polarity range e. e. from chloroform (Z, 63.2) to methanol (Z .83.6). Transition energies and oscillator strengths have been calculated and transition energy (E_T) has been plotted against Z-values, a new empirical measurement of solvent polarity. A linear relationship was observed between the transition energy and Z-values for π → π* and n → π* transitions. These transitions are identified as charge transfer (c-t) transitions and with the solvents having carbonyl oxygen and sulphur atom a c-t complex formation has been suggested. Strong electron-donating substituents on phenyl group of the nitrogen atom also showed a weak to moderate n → π* transitions. These substituents have no influence on the position of the λ_max in the same solvent. Stabilization energy of the excited state of these ligands and hence the dipole moments of the excited states have been calculated in comparison with pyridinium iodide. Solvent sensitivities of these ligands have also been calculated.     

Stereoselectivity and nonmigratory insertion mechanism of dimethylacetylene dicarboxylate into metallocene-hydride of Cp2M(L)H [Cp = η5-C5H5; M = Nb,V; L = CO,P (OMe)3]: A DFT study

The insertion of an alkyne into transition metal–hydrogen bonds is a key elementary step in catalytic polymerization and hydrogenation processes. It was found that a (Z)- or (E)-type alkyenyl complex can be formed through trans/cis stereospecific processes. In this work, the reaction mechanism of Cp₂M(L)H [Cp = η⁵-C₅H₅; M = Nb, V; L = CO, P (OMe)₃] with dimethylacetylene dicarboxylate (DMAD), and the factors influencing the stereoselectivity have been investigated based on density functional theory calculations. The calculated results show that all of the reactions are exothermic. For L = CO, the Z-isomer product forms first even at low temperatures because of the low Gibbs free energy barrier (ΔG^#). Then the Z-pro converts to E-pro , while for L = P (OMe)₃, the exclusive product is the E-isomer. For different metal centers, the reaction mechanisms of the Cp₂M(CO)H + DMAD (M = Nb and V) reaction are similar, while their products are different at room temperature. For M = Nb, because the energy barrier of the isomerization from Z-pro to E-pro is low and the relative free energies of Z-pro and E-pro are almost equal, both Z-pro and E-pro can be obtained. While for the Cp₂V(CO)H + DMAD reaction, only the Z-pro can be obtained under mild conditions, E-pro can be obtained only at high temperatures. For the Cp₂M(CO)H+DMAD(M=V and Nb) reactions, the formation of E-isomer products proceeds via two five-membered ring transition states. The calculated results provide an reasonable explanation for the experimental results and predict a new insertion reaction.     

Large-Z and -N dependence of atomic energies from renormalization of the large-dimension limit

By combining Hartree–Fock results for nonrelativistic ground-state energies of N-electron atoms with analytic expressions for the large-dimension limit, we have obtained a simple renormalization procedure. For neutral atoms, this yields energies typically threefold more accurate than the Hartree–Fock approximation. Here, we examine the dependence on Z and N of the renormalized energies E(N, Z) for atoms and cations over the range Z, N = 2 → 290. We find that this gives for large Z = N an expansion of the same form as the Thomas–Fermi statistical model, E → Z^7/2(C₀ + C₁Z^?1/3 + C₂Z^?2/3 + C₃Z^?3/3 + ?), with similar values of the coefficients for the three leading terms. Use of the renormalized large-D limit enables us to derive three further terms. This provides an analogous expansion for the correlation energy of the form δE δZ^4/3(δC₃ + δC₅Z^?2/3 + δC₆Z^?3/3 + ?); comparison with accurate values of δE available for the range Z ? 36 indicates the mean error is only about 10%. Oscillatory terms in E and δE are also evaluated. © 1994 John Wiley & Sons, Inc.     

1-(Nitrosoamino)benzimidazoles Containing Electron-acceptor Substituents at the Amine Nitrogen. Theoretical and Experimental Investigation of Conformational Mobility

The previously unknown 1-(N-nitrosoallylamino)- and 1-(N-nitrosopropargylamino)benzimidazoles have been synthesized and they exist in solution as a mixture of the E- and Z-conformers due to hindered rotation around the N-N(O) bond. The activation energies for the EZ transition in these compounds and for the model N-benzyl analog have been determined by a dynamic ¹H NMR method. With a view to studying the effect of a substituent at the amino nitrogen on the EZ isomerization we have carried out 3-21G and 6-31G** type ab initio calculations of the stable conformers of a series of N-nitrosohydrazines.     

Effect of Solvents on the Spectra of Some N′-2-(Substituted Pyridyl)-N-Substituted-Thioureas

Some N′-2-(substituted pyridyl)-N-substituted thiourea (in all 12-substituted pyridyl thioureas) have been examined in ultraviolet region in a series of solvents covering a broad polarity range i. e. from benzene (Z, 54.0) to ethylene glycol (Z, 85.1). Transition energies and oscillator strengths have been calculated and transition energy (E_T) has been plotted against Z-values, a new-empirical measurement of solvent polarity. A linear relationship was observed between the transition energy and Z-value for pyridyl μ→μ* and thiocarbonyl μ→μ* transitions. The effect of substituent present in pyridyl group on λ_max of a compound in the same solvent has been studied. Solvent sensitivites of these ligands have also been calculated.     

NMR of enaminones. Part 7 1H-, 13C-, and 17O-NMR and X-ray structure determinations of 1,2-disubstituted conjugated 3-[(tert-Butyl)amino]enones

¹H-, ¹³C-, and ¹⁷O-NMR spectra for the 2-substituted enaminones MeC(O)C(Me)?CHNH(t-Bu) ( 1 ), EtC(O)C(Me)?CHNH(t-Bu) ( 2 ), PhC(O)C(Me)?CHNH(t-Bu) ( 3 ), and MeC(O)C(Me)?CHNH(t-Bu) ( 4 ) are reported. These data show that 3 exists mainly in the (E)-form, 4 in (Z)-form, and 1 and 2 as mixtures of both forms. Polar solvents favour the (E)-form. The (Z)- and (E)-forms exist in the 1,2-syn,3,N-anti and 1,2-anti,1,N-anti conformations A and B , respectively. The structures of the (E)- and (Z)-form are confirmed by X-ray crystal-structure determinations of 3 and 4. The shielding of the carbonyl O-atom in the ¹⁷O-NMR spectrum by intramolecular H-bonding (Δλ_HB) ranging from ?28 to ?41 ppm, depends on the substituents at C(l) and C(2). Crystals of 3 at 90 K are monoclinic. with a = 9.618(2) Å, b = 15.792(3) Å, c = 16.705(3) Å, and β = 94.44(3)°, and the space group is P2₁/c with Z = 8 (refinement to R = 0.0701 on 3387 independent reflections). Crystals of 4 at 101 K are monoclinic, with a = 16.625(8) Å, b = 8.637(6) Å, c = 11.024(7) Å, and β = 101.60(5)°, and the space group is Cc with Z = 4 (refinement to R = 0.0595 on 2106 independent reflections).     

Two Highly Stable Proton Conductive Cobalt(II)–Organic Frameworks as Impedance Sensors for Formic Acid

Metal–organic frameworks (MOFs) have been extensively explored as advanced chemical sensors in recent years. However, there are few studies on MOFs as acidic gas sensors, especially proton conductive MOFs. In this work, two new proton-conducting 3D MOFs, {[Co₃(p-CPhHIDC)₂(4,4′-bipy)(H₂O)] ⋅ 2 H₂O}_n ( 1 ) (p-CPhH₄IDC=2-(4-carboxylphenyl)-1 H-imidazole-4,5-dicarboxylic acid; 4,4′-bipy=4,4′-bipyridine) and {[Co₃(p-CPhHIDC)₂(bpe)(H₂O)] ⋅ 3 H₂O}_n ( 2 ) (bpe=trans-1,2-bis(4-pyridyl)ethylene) have been solvothermally prepared and investigated their formic acid sensing properties. Both MOFs 1 and 2 show temperature- and humidity-dependent proton conductive properties and exhibit optimized proton conductivities of 1.04×10⁻³ and 7.02×10⁻⁴ S cm at 98 % relative humidity (RH) and 100 °C, respectively. The large number of uncoordinated carboxylic acid sites, free and coordination water molecules, and hydrogen-bonding networks inside the frameworks are favorable to the proton transfer. By measuring the impedance values after exposure to formic acid vapor at 98 % or 68 % RH and 25 °C, both MOFs indicate reproducibly high sensitivity to the analyte. The detection limit of formic acid vapor is as low as 35 ppm for 1 and 70 ppm for 2 . Meanwhile, both MOFs also show commendable selectivity towards formic acid among interfering solutions. The proton conducting and formic acid sensing mechanisms have been suggested according to the structural analysis, E_a calculations, N₂ and water vapor absorptions, PXRD and SEM measurements. This work will open a new avenue for proton-conductive MOF-based impedance sensors and promote the potential application of these MOFs for indirectly monitoring the concentrations of formic acid vapors.     

Conformational analysis of 2-substituted nitroethenes

Experimental and theoretical conformational analysis of polyfunctional 2-substituted nitroethenes was carried out by the method of dipole moments and density functional theory calculations. It was established that the nitro and ester (or trichloromethyl) groups are trans-arranged in the molecules of 2-trichloromethyl-(ethoxycarbonyl)-1-nitro- and 1-bromo-1-nitroethenes, i.e., nitroalkenes have E-configuration, their bromo-containing analogues have Z-configuration, and s-cis-orientation of the C=C and C=O double bonds is preferred for nitroacrylates. 2,3-Dibromo-3-nitroacrylates have untrivial Z-configuration in solution.     

Z‐sinapinic acid: the change of the stereochemistry of cinnamic acids as rational synthesis of a new matrix for carbohydrate MALDI‐MS analysis

Successful application of matrix‐assisted laser desorption/ionization (MALDI) MS started with the introduction of efficient matrices such as cinnamic acid derivatives (i.e. 3,5‐dimethoxy‐4‐hydroxycinnamic acid, SA; α‐cyano‐4‐hydroxycinnamic acid). Since the empirical founding of these matrices, other commercial available cinnamic acids with different nature and location of substituents at benzene ring were attempted. Rational design and synthesis of new cinnamic acids have been recently described too. Because the presence of a rigid double bond in its molecule structure, cinnamic acids can exist as two different geometric isomers, the E‐form and Z‐form. Commercial available cinnamic acids currently used as matrices are the geometric isomers trans or E (E‐cinnamic and trans‐cinnamic acids). As a new rational design of MALDI matrices, Z‐cinnamic acids were synthesized, and their properties as matrices were studied. Their performance was compared with that of the corresponding E‐isomer and classical crystalline matrices (3,5‐dihydroxybenzoic acid; norharmane) in the analysis of neutral/sulfated carbohydrates. Herein, we demonstrate the outstanding performance for Z‐SA. Sulfated oligosaccharides were detected in negative ion mode, and the dissociation of sulfate groups was almost suppressed. Additionally, to better understand the quite different performance of each geometric isomer as matrix, the physical and morphological properties as well as the photochemical stability in solid state were studied. The influence of the E/Z photoisomerization of the matrix during MALDI was evaluated. Finally, molecular modeling (density functional theory study) of the optimized geometry and stereochemistry of E‐cinnamic and Z‐cinnamic acids revealed some factors governing the analyte–matrix interaction. Copyright © 2013 John Wiley & Sons, Ltd.     

Structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone as chiral component of liquid-crystalline systems

The spatial structure of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone prepared by photochemical isomerization of the E-isomer was studied by analyzing the magnitudes and temperature dependence of the proton spin-spin coupling constants obtained by ¹H NMR spectroscopy and the results of molecular modeling using semiempirical quantum chemical AM1 and PM3 methods and the density functional theory (DFT). Comparison of the results obtained for the Z-and E-isomers shows that in both cases the conformational equilibrium for both isomers is characterized by significant preference of the chair conformer having an equatorial methyl group, namely, − ΔH (chair a ⇌ chair e) = 1.98–2.12 and 1.36–1.54 kcal mole⁻¹ for the Z-and E-isomers, respectively. Distinctions in the non-planarity of the enone fragment and cyclohexanone ring in the Z-and E-isomers under study following from the results of mathematical modeling were confirmed by the experimental values of the geminal spin-spin coupling constants of protons of the methylene groups in α,α ′-positions with respect to the enone group. Quantum chemical calculations of the Z-isomer revealed the existence of intramolecular hydrogen bond between the carbonyl oxygen and the nearest aromatic proton in ortho-position of the benzene ring. Possible reasons for different helical twisting power of (Z)-(5R)-methyl-2-(4-phenylbenzylidene)cyclohexanone and the E-and Z-arylidene derivatives of 1R, 4R-isomenthone in the mesophase are discussed based on the results of molecular structure studies for these compounds. In the text below the unsaturated ketones under study will be called “arylidene cyclohexanone derivatives” for convenience of comparing the characteristics of methylcyclohexanone and isomenthone derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 962–972, June, 2006.     

Phosphoric acid catalyzed enantioselective transfer hydrogenation of imines: a density functional theory study of reaction mechanism and the origins of enantioselectivity

The phosphoric acid catalyzed reaction of 1,4‐dihydropyridines with N‐arylimines has been investigated by using density functional theory. We first considered the reaction of acetophenone PMP‐imine (PMP=p‐methoxyphenyl) with the dimethyl Hantzsch ester catalyzed by diphenyl phosphate. Our study showed that, in agreement with what has previously been postulated for other reactions, diphenyl phosphate acts as a Lewis base/Brønsted acid bifunctional catalyst in this transformation, simultaneously activating both reaction partners. The calculations also showed that the hydride transfer transition states for the E and Z isomers of the iminium ion have comparable energies. This observation turned out to be crucial to the understanding of the enantioselectivity of the process. Our results indicate that when using a chiral 3,3′‐disubstituted biaryl phosphoric acid, hydride transfer to the Re face of the (Z)‐iminium is energetically more favorable and is responsible for the enantioselectivity, whereas the corresponding transition states for nucleophilic attack on the two faces of the (E)‐iminium are virtually degenerate. Moreover, model calculations predict the reversal in enantioselectivity observed in the hydrogenation of 2‐arylquinolines, which during the catalytic cycle are converted into (E)‐iminium ions that lack the flexibility of those derived from acyclic N‐arylimines. In this respect, the conformational rigidity of the dihydroquinolinium cation imposes an unfavorable binding geometry on the transition state for hydride transfer on the Re face and is therefore responsible for the high enantioselectivity.     

An ab initio interpretation in gas phase and aqueous solution of the generalized anomeric effect in R?O?CR2?NR2 (R = H,CH3)

The conformational stability of aminomethanol and its methylated derivatives has been investigated by means of ab initio methods in the gas phase and aqueous solution. Among the computational levels employed, HF/6‐31G**//HF/6‐31G** calculations correctly describe the conformational features of this series of compounds, and agree well with the results obtained using larger basis sets and including ZPE or electron correlation corrections. Calculated energies and geometries follow the known trends associated to the generalized anomeric effect. Thus, the most stable conformers exhibit preferences for the trans orientations of the Lp N C O and Lp O C N moieties. However, reverse anomeric effects are observed when a methyl group is bonded to the oxygen, because the Lp O C N unit prefers a gauche orientation (that is, trans Me O C N). The natural bond orbital (NBO) method was employed to explain the cited conformational preferences. According to the NBO results, trans arrangements are preferred because the stabilization due to charge delocalization is more important than electrostatic and steric contributions. This explanation agrees with the conclusions obtained by other independent procedures based on energy decomposition schemes. The NBO method was also used to explain the origin of the rotational barriers around the C O and C N bonds in terms of the balance between unfavorable hyperconjugation and electrostatic and steric effects. Changes in conformational stability caused by methylations in different molecular positions were also explained by the influence of the methyl groups on lone‐pair delocalization and on steric effects. Finally, the effect of solvation was studied by means of the ab initio PCM method, and the significant changes on relative energies found were analyzed. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 462–477, 2000     

Peptide models XXIII. Conformational model for polar side‐chain containing amino acid residues: A comprehensive analysis of RHF,DFT, and MP2 properties of HCO‐L‐SER‐NH2

Geometric and energetic properties of a diamide of serine, HCO‐NH‐L ‐CH(CH₂OH)CO‐NH₂, are investigated by standard methods of computational quantum chemistry. Similarly to other amino acid residues, conformational properties of HCO‐L ‐Ser‐NH₂ can be derived from the analysis of its E=E(ϕ,ψ;χ₁,χ₂) hypersurface. Reoptimization of 44 RHF/3‐21G conformers at the RHF/6‐311++G** level resulted in 36 minima. For all conformers, geometrical properties, including variation of H‐bond parameters and structural shifts in the torsional space, are thoroughly investigated. Results from further single‐point energy calculations at the RHF, DFT, and MP2 levels, performed on the entire conformational data set, form a database of 224 energy values, perhaps the largest set calculated so far for any single amino acid diamide. A comprehensive analysis of this database reveals significant correlation among energies obtained at six levels of ab initio theory. Regression parameters provide an opportunity for extrapolation in order to predict the energy of a conformer at a high level by doing explicit ab initio computations only for a few selected conformers. The computed conformational and relative energy data are compared with structural and occurrence results derived from a nonhomologous protein database incorporating 1135 proteins. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 626–655, 2000     

Exploring concomitant/conformational dimorphism in a difluoro‐substituted phosphoramidate derivative

The concomitant occurrence of dimorphs of diphenyl (3,4‐difluorophenyl)phosphoramidate, C₁₈H₁₄F₂NO₃P, was observed via a solution‐mediated crystallization process with variation in the symmetry‐free molecules (Z′). The existence of two forms, i.e. Form I (block, Z′ = 1) and Form II (needle, Z′ = 2), was characterized by single‐crystal X‐ray diffraction, differential scanning calorimetry and powder X‐ray diffraction. Furthermore, a quantitative analysis of the energetics of the different intermolecular interactions was carried out via the energy decomposition method (PIXEL), which corroborates with inputs from the energy framework and looks at the topology of the various intermolecular interactions present in both forms. The unequivocally distinguished contribution of strong N—H…O hydrogen bonds along with other interactions, such as C—H…O, C—H…F, π–π and C—H…π, mapped on the Hirshfeld surface is depicted by two‐dimensional fingerprint plots. Apart from the major electrostatic contribution from N—H…O hydrogen bonds, the crystal structures are stabilized by contributions from the dispersion energy. The closely related melting points and opposite trends in the calculated lattice energies are interesting to investigate with respect to the thermodynamic stability of the observed dimorphs. The significant variation in the torsion angles in both forms helps in classifying them in the category of conformational polymorphs.     

Mechanism and Stereoselectivity of the Elementometalation Process of Activated Alkyne RCCR(RCO2Me) by Cp2TaH3

The elementometalation process is a fundamental chemical step in several catalytic cycles. In this work, density functional theory computations have elucidated the detailed elementometalation mechanism of activated alkyne RCCR(RCO₂Me) by Cp₂TaH₃ and rationalized the selectivity in experimental findings. The calculated results show that in the formation process of (E)-olefin monohydride((E)-Pro), the Gibbs free energy barrier is low and the entire reaction is spontaneous and exothermic; thus, (E)-Pro can be formed easily. The formation of (Z)-η²-olefin monohydride complex ((Z)-Pro) is difficult due to its high Gibbs free energy barrier. The formation process (E)-Pro consists of the following five steps: hydride H1-shift, conformational isomerism 1, hydride H2-shift, conformational isomerism 2, and olefin coordination process. Topological analysis shows that there is a five-membered ring plane structure in the reaction pathway and that the final product (E)-Pro belongs to a typical η²-olefin monohydride complex. Our calculated results provide an explanation for experimental observations and useful insights for further development of olefin functionalization. © 2019 Wiley Periodicals, Inc.     

ss‐NMR and single‐crystal X‐ray diffraction in the elucidation of a new polymorph of bischalcone (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one

We report a new polymorph of (1E,4E)‐1,5‐bis(4‐fluorophenyl)penta‐1,4‐dien‐3‐one, C₁₇H₁₂F₂O. Contrary to the precedent literature polymorph with Z′ = 3, our polymorph has one half molecule in the asymmetric unit disordered over two 50% occupancy sites. Each site corresponds to one conformation around the single bond vicinal to the carbonyl group (so‐called anti or syn). The other half of the bischalcone is generated by twofold rotation symmetry, giving rise to two half‐occupied and overlapping molecules presenting both anti and syn conformations in their open chain. Such a disorder allows for distinct patterns of intermolecular C—H…O contacts involving the carbonyl and anti‐oriented β‐C—H groups, which is reflected in three ¹³C NMR chemical shifts for the carbonyl C atom. Here, we have also assessed the cytotoxicity of three symmetric bischalcones through their in vitro antitumour potential against three cancer cell lines. Cytotoxicity assays revealed that this biological property increases as halogen electronegativity increases.