Pyrazole Ring Research Articles

Synthesis, characterization and photophysical properties of phthalimide-pyrazole compounds: Effect of the substituent in the pyrazole ring on the crystal structures

Four phthalimide-pyrazole derivative compounds (L1 = H, L2 = NO2, L3 = Br, and L4 = I) were synthesized and fully characterized. Single crystals of each compound were obtained, and their conformational and supramolecular structures were analyzed. The four crystal structures (L1 to L4) are stabilized by different intermolecular interactions and therefore have different characteristics from each other. L1 is dominated by long-range Van der Waals forces and not by short hydrogen bonds. On the other hand, L2 packs into a molecular sheet along the b and c axes. L3 and L4 have a common monoclinic structure (P21/c) and thus allow stabilization of the respective compounds by halogen-halogen interactions (Br–Br, I–I) and σ-hole effects. In all compounds, these interactions, whether Van der Waals forces, π‧‧‧‧π stacking or halogen bonds, are responsible for their packing and molecular stability. Therefore, it was concluded that the substituent on the pyrazole ring is the determining factor in their crystallization. In addition, photophysical and theoretical studies showed that the compounds exhibit emission in the presence of DCM, acetonitrile (MeCN), and DMSO, primarily due to the HOMO-LUMO orbitals in the phthalimide ring.

Theoretical exploration of energetic molecular design strategy: functionalization of C or N and structural selection of imidazole or pyrazole.

In researching energetic materials with high energy density, it is an effective method to introduce explosophoric groups. In this study, four series of energetic compounds were designed by functionalizing with C- or N-, introducing energetic groups -CH(NO2)2, -CF(NO2)2, -C(NO2)2(NF2), -C(NO2)3, and-CH(NF2)2 into imidazole and pyrazole structures. Density functional theory was employed to optimize the structure of the target compound and subsequently to predict and evaluate its performance based on this. Meanwhile, the sensitivity of the compounds was predicted based on their electrostatic potential analysis. Following analysis of the geometric structure, detonation performance, and sensitivity of the compounds, three factors were discussed: energetic groups, functionalization methods, and skeleton structure differences. The results indicate that C-functionalization has advantages only in density, but N-functionalization is better in thermal stability, heat of formation, and sensitivity. Meanwhile, the data shows that imidazole-based compounds exhibited greater density and detonation performance in the target compounds designed within this study, while pyrazoles have a higher heat of formation and chemical stability. By analyzing the design strategy of C- or N-functionalization of novel high-energy groups on energetic imidazole or pyrazole rings and selecting a more suitable molecular construction strategy, this study provides a theoretical approach for the development of new energetic materials with excellent performance. Gaussian 09 and Multiwfn 3.8 packages are the software used for calculation, and the electrostatic potentials were depicted using the VMD program. In this study, the imidazole and pyrazole derivatives were optimized at the B3PW91/6-311G (d, p) level to acquire the relevant data for the compounds.

Enhancing Performance and Stability of Perovskite Solar Cells with a Novel Formamidine Group Additive.

Perovskite materials, particularly FAPbI3, have emerged as promising candidates for solar energy conversion applications. However, these materials are plagued by well-known defects and suboptimal film quality. Enhancing crystallinity and minimizing defect density are therefore essential steps in the development of high-performance perovskite solar cells. In this study, 1H-Pyrazole-1-carboximidamide hydrochloride (PCH) is introduced into FAPbI3 perovskite films. The molecular structure of PCH features a pyrazole ring bonded to formamidine (FA). The FA moiety of PCH facilitated the incorporation of this additive into the film lattice, while the negatively charged pyrazole ring effectively passivated positively charged iodine vacancies. The presence of PCH led to the fabrication of an FAPbI3 device with improved crystallinity, a smoother surface, and reduced defect density, resulting in enhanced Voc and fill factor. A record power conversion efficiency of 24.62% is achieved, along with exceptional stability under prolonged air exposure and thermal stress. The findings highlight the efficacy of PCH as a novel additive for the development of high-performance perovskite solar cells.

The Role of the Nitro Group on the Formation of Intramolecular Hydrogen Bond in the Methyl Esters of 1-Vinyl-Nitro-Pyrazolecarboxylic Acids

All reactions involving the nitrogen atom in 3(5)-substituted pyrazoles inevitably lead to a mixture of N-substituted 3- and 5- isomers due to tautomerism. The position of substituent can affect the behavior of N-vinyl isomers, in particular, the ability of some functional groups to form =C-H...O or =C-H...N weak hydrogen bonding type interaction with α-hydrogen of vinyl group due to steric reasons. Moreover, the additional substituents in the pyrazole ring can further influence the possibility and nature of specific intramolecular interactions. Here we have shown the effect of the nitro group on the formation of hydrogen bonds in methyl esters of 1-vinyl-4-nitro-3(5)- and 1-vinyl-5-nitro-3(5)-pyrazole carboxylic acids. A comprehensive study, including synthesis, quantum chemical calculations, NMR and XRD analysis, allowed to conclude that, contrary to expected, in the methyl ester of 1-vinyl-4-nitro-5-pyrazolecarboxylic acid, the formation of a planar conformation is unfavorable, preventing formation of a classical hydrogen bond. On the other hand, there is a hydrogen bond between the nitro group and vinyl group in 1-vinyl-5-nitro-pyrazolecarboxylic acids.

Studi Molecular Docking dan Evaluasi Farmakokinetik Senyawa Analog Pirazol Turunan Benzen-Sulfonilurea sebagai Inhibitor Enzim Aldose Reduktase and α-Glukosidase Menggunakan Pendekatan In Silico

The pyrazole scaffold modification in various chemical structures on several studies has shown various biopharmacological activities. This study aims to predict the potential inhibition of pyrazole analogs derived benzene-sulfonylurea (4A, 4B, 4E, 5A, 5C, 5D) against the α-glucosidase (3A4A) and aldose reductase (3RX2) enzymes based on a molecular docking approach using Molecular Operating Environment (MOE) 2020.0102 software and evaluate pharmacokinetic profile (ADMET). In this study, the six test compounds were obtained from previous studies that have been proven antihyperglycemic. The results showed that all the 3,5-disubstituted benzene-sulfonylurea derivative pyrazole analogs are predicted to have low inhibitory activity against the α-glucosidase enzyme. Further, all compounds showed good aldose reductase inhibitor activity and had lower binding free energy values ​​than tolrestat as the positive control (-6.82 kcal/mol). Compound 5C has the best potential inhibitory activity against the aldose reductase enzyme compared to the other test compounds, because it has the lowest binding free energy value (-8.76 kcal/mol) and interacts with important residues on the receptor forming four hydrogen bonds, namely the carbonyl group of SO2 with residues Trp111 and His110, and the carbonyl group of the amide with residues His110 and Tyr48, as well as 3 hydrophobic bonds, namely a pyrazole ring with residues Leu300, Trp219 and a furan ring with Phe122. ADMET properties of the compounds are also predicted. This information provides an opportunity for a 5C compound as an aldose reductase inhibitor agent to develop drug candidates with better and safer activities.

First Alliance of Pyrazole and Furoxan Leading to High-Performance Energetic Materials.

Nitrogen heterocyclic scaffolds retain their leading position as valuable building blocks in material science, particularly for the design of small-molecule energetic materials. However, the search for more balanced combinations of directly linked heterocyclic cores is far from being exhausted and aims to reach ideally balanced high-energy substances. Herein, we present the synthetic route to novel pyrazole-furoxan framework enriched with nitro groups and demonstrate a promising set of properties, viz., good thermal stability, acceptable mechanical sensitivity, and high detonation performance. In-depth crystal analysis showed that the isomers having lower-impact sensitivity values in both types of regioisomeric pairs are those with the exocyclic furoxan oxygen atom being closer to the pyrazole ring. Owing to the favorable combination of high crystal densities (1.83-1.93 g cm-3), positive oxygen balance to CO (up to +13.9%), and high enthalpies of formation (322-435 kJ mol-1), the synthesized compounds show high calculated detonation velocities (8.4-9.1 km s-1) and excellent metal accelerating abilities. The incorporation of the 3-nitrofuroxan moiety increases the thermal stability (by ca. 20 °C) and decreases the mechanical sensitivity of target hybrid materials in both types of regioisomeric pairs. Simultaneously, the detonation performance of 3-nitrofuroxans is almost identical to that of 4-nitrofuroxans, highlighting the potential of the regioisomeric tunability in the future design of energetic materials.

Development of new pyrazoles as class I HDAC inhibitors: Synthesis, molecular modeling, and biological characterization in leukemia cells.

Class I histone deacetylases (HDACs) are considered promising targets in current cancer research. To obtain subtype-selective and potent HDAC inhibitors, we used the aminobenzamide scaffold as the zinc-binding group and prepared new derivatives with a pyrazole ring as the linking group. The synthesized compounds were analyzed in vitro using an enzymatic assay against HDAC1, -2, and -3. Compounds 12b, 15b, and 15i were found to be potent HDAC1 inhibitors, also in comparison to the reference compounds entinostat and tacedinaline, with IC50 values of 0.93, 0.22, and 0.68 μM, respectively. The best compounds were measured for their cellular effect and target engagement in acute myeloid leukemia (AML) cells. In addition, we studied the interaction of the compounds with HDAC subtypes using docking and molecular dynamic simulations. In summary, we have developed a new chemotype of HDAC1 inhibitors that can be used for further structure-based optimization.

Anticancer and anti-inflammatory effects of novel ethyl pyrazole derivatives having sulfonamide terminal moiety

In the present work, a new series of ethyl pyrazole-containing compounds with side sulphonamide moiety was designed and synthesized. The new derivatives were divided into four groups based on the linker between the sulphonamide and pyridine ring attached to position 4 of the pyrazole ring and the substitution on the phenyl ring at position 3 of the same ring. The linker could be ethyl or propyl linkers. The phenyl ring is substituted with a methoxy group or hydroxyl group at position 3. The aim compounds were tested for their JNK1, JNK2, JNK3, and BRAF(V600E) activities. Compounds 23b, 23c, and 23d showed the highest activity with nanomolar IC50s. The most potent compound over JNK1 was 23d with an IC502 nM. While compound 23c was the most potent over JNK2 with an IC5057 nM. Finally, compound 23b was the most potent over JNK2 and BRAF(V600E) with IC50s of125 nM and 98 nM, respectively. After obtaining kinase inhibitory activity, the compounds were submitted to NCI to test their activity over different cell lines. Compound 23b showed the highest activity over most tested cell lines. In the second part of the present study, the final target compounds were tested for their anti-inflammatory effect. The anti-inflammatory effect of the new final compounds was performed by measuring their ability to inhibit inducible nitric oxide release and prostaglandin E2 production inhibition. Compound 23c showed the highest activity regarding nitric oxide release with IC50 0.63 μM, while compound 21d had the highest activity regarding prostaglandin E2 production with IC50 0.52 μM. The effect of the most potent compounds was tested by western blot against iNOS, COX-1, and COX-2.

(E)-1-(3,4-Di-meth-oxy-phen-yl)-3-(1,3-diphenyl-1H-pyrazol-4-yl)prop-2-en-1-one.

In the title compound, C26H22N2O3, the dihedral angle between the benzene and pyrazole rings of the chalcone unit is 88.3 (1)°. The pyrazole ring has two attached phenyl rings that form dihedral angles with the pyrazole ring of 22.6 (2) and 40.0 (1)°. In the crystal, pairwise C-H⋯O hydrogen bonds generate R 2 2(20) inversion dimers.

Chemo- and regioselective controlled synthesis and thermal analysis characterization of trifluoromethyl polypyrazoles

This study details the chemo- and regioselective synthesis and spectroscopic and thermal analysis characterization of trifluoromethyl bipyrazoles and polypyrazoles by stepwise N-alkylation of pyrazoles using (E)-4-(amino)-5-bromo-1,1,1-trifluoro-but-3-en-2-ones (5-bromo enaminones), followed by cyclocondensation of the enaminone moiety with hydrazines. A mechanism for the cyclocondensation reaction was proposed. Sixteen new methylene-bridged bipyrazoles and polypyrazole chains with up to five pyrazole units were achieved at very good yields. All the compounds were characterized by 1H and 13C NMR, and the 1,3-regiochemistry was evidenced by single-crystal X-ray diffraction. The polypyrazoles’ thermal behavior was elucidated by thermogravimetric analysis and differential scanning calorimetry. It is suggested that at approximately 300°C the polypyrazoles thermally decompose independent of the number of repeating units. The second and third heating/cooling cycles of the differential scanning calorimetry indicate that the majority of the polypyrazoles are amorphous materials, with glass transition values that can be tuned by the number of repeating units in the polymeric chain and the type of linkage between the pyrazole rings.

Synthesis, crystal structure, density functional theory, drug-likeness, and molecular docking studies of a new carbazole-pyrazole derivative: A potential inhibitor of tuberculosis

In this study, a compound combining a carbazole moiety with a pyrazole ring (4E)-4-((9-ethyl-9H-carbazol-3-yl)methyleneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one was synthesized and evaluated for its potential as an effective tuberculosis (TB) inhibitor. Compound 3 was synthesized by the condensation of 9-ethylcarbazole-3-carbaldehyde (1) with 4-amino-1,2-dihydro-2,3-dimethyl-1-phenyl-1H-pyrazol-5-one (2), and its 3D pose was employed by X-ray crystallography. The crystal structure analysis revealed the precise arrangement of atoms and provided insights into the compound's three-dimensional arrangement, which is crucial for understanding its interactions with biological targets. To assess the compound's pharmacokinetic properties and potential toxicity, an absorption, distribution, metabolism, excretion, and toxicity study was implemented. The results indicated satisfactory bioavailability and showed limited toxicity risks, suggesting a favorable safety profile. To gain insights into the compound's binding interactions of the compound with the target protein involved in TB, molecular docking studies were carried out. The docking results supported its potential as a TB inhibitor by highlighting its ability to establish favorable interactions within the binding pocket.. KEYWORDS :ADMET, Carbazole cum pyrazole, Crystal structure, DFT, Docking, Drug-likeness.

Discovery of new molecular hybrid derivatives with coumarin scaffold bearing pyrazole/oxadiazole moieties: Molecular docking, POM analyses, in silico pharmacokinetics and in vitro antimicrobial evaluation with identification of potent antitumor pharmacophore sites

This synthetic organic methodology involves the creation of novel coumarin-based hybrids of series (1–4) with pyrazole ring and (5–8) with oxadiazole moiety. The targeted compounds were tested for In vitro Antimicrobial efficacy against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans pathogenic microbes using disc diffusion and broth microdilution with ciprofloxacin and fluconazole as reference standards. Density functional theory (DFT) studies were used to study atomic structure and reactivity, including absolute electronegativity (χ), electrophilicity (ω), electron acceptor (ω+), donor capabilities (ω–), electron affinity (EA), energy gap (ΔE), global hardness (η), global softness (S), and ionisation potential (IP) and FMOs, NBOs, MEP, and Mulliken Charge analysis. The POM tests found three integrated pharmacophore sites with antibacterial, antiviral, and anticancer activities. Molecular docking studies are also used to determine the S. aureus nucleoside diphosphate kinase receptor’s affinity and mode of action for the synthesized drugs. In silico analysis of thermodynamic and therapeutic effectiveness properties, including Lipinski’s ’rule of five’, Veber’s rule, and ADME properties, predicted toxicity-free, non-carcinogenic, and risk-free oral administration of the synthesized complexes.

Efficient Synthesis and Iodine-Functionalization of Pyrazoles via KIO3/PhSeSePh System under Acidic Conditions.

This manuscript reports a novel method for the direct iodination of the C-4 pyrazole ring generated in situ by the reaction of 1,1,3,3-tetramethoxypropane and various hydrazines. In this approach, potassium iodate (KIO3) is used as the iodinating agent and (PhSe)2 is used as catalysts under acidic conditions. This protocol provides a convenient method for the efficient synthesis of 4-iodo-1-aryl-1H-pyrazoles, valuable intermediates for several different coupling reactions.

Kinetic studies, molecular docking, and antioxidant activity of novel 1,3-diphenyl pyrazole-thiosemicarbazone with anti-tyrosinase and anti-melanogenesis properties

This study reports the Design Hypothesis of a novel series of 1,3-diphenyl pyrazole-thiosemicarbazone as novel tyrosinase inhibitors (TYRI). The designed compounds were prepared and their TYRI activity and mechanisms were studied. The results showed that the selected compounds exhibited potent tyrosinase inhibitory activities greater than that of kojic acid (KA). Lead candidates, denoted as 6g and 6n, with a para-hydroxyphenyl group attached to the 3-position of the pyrazole ring demonstrated IC50 values of 2.09 and 3.18 µM, respectively. The potency of these compounds was approximately 5–8 times higher than that of KA. The in vitro melanin content of 6g or 6n-treated melanoma cells resulted in significant efficacy in melanin reduction. The DPPH assay result revealed that the tyrosinase inhibition mechanism for these derivatives was independent of a redox effect and corresponded to the interaction with tyrosinase. According to the Lineweaver-Burk plot, the most potent compounds, 6g and 6n, exhibit a mixed type of inhibition, primarily noncompetitive inhibition. In silico molecular docking studies were employed to determine the binding mode and explore the Design Hypothesis in detail. The results suggested that these compounds could be considered promising leads for the further development of novel inhibitors to treat disorders related to tyrosinase.

Synthesis, characterization, and dyeing performance of Novel Bisazo disperse dyes: A combined spectroscopic and computational study

Disperse dyes are a versatile class of coloring agents with applications spanning textiles to advanced optical materials. This study details the synthesis and spectroscopic characterization of innovative bisazo disperse dyes, which are derived from benzidine-based compounds. The synthetic process involves the use of two distinct couplers, namely acetylacetone and ethyl acetoacetate. The reaction of these couplers with benzidine derivatives yields two specific bisazo dyes: diethyl 2,2′-(2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(hydrazin-2-yl-1-ylidene))bis(3-oxobutanoate) 3 and 3,3′-(2,2′-([1,1′-biphenyl]-4,4′-diyl)bis(hydrazin-2-yl-1-ylidene))bis(pentane-2,4‑dione) 4. The reaction of these azo compounds with hydrazine and phenylhydrazine results in the formation of azo dyes that incorporate a pyrazole ring 5–7. All the disperse azo compounds were characterized and identified through various spectroscopic methods, including UV-visible, FT-IR, NMR (both 1H and 13C), and elemental analysis. Examining the UV–vis profiles of the disperse dyes 3–7 revealed the maximum absorbance values (λmax) were affected by the change of the coupler moieties and more significant sensitivity to changes in pH. The polyester fabric (PE-F) was dyed by disperse dyes 3–7 in presence of the dispersing agent DYEWELL-002 and the fastness data were measured according to the standard procedures. The color strength (K S-1) and exhaustion (%E) values of the dyed fabrics are calculated and discussed. The synthesised bisazo dyes were subjected to computational calculations using DFT with B3LYP method and 6–31G(d,p) basis set to examine the dyeing efficiencies and anticipate the mechanism of the dyeing process. The computational analyses assessed the dipole moment, chemical reactivity descriptors and molecular electrostatic potential. Analysis of the chemical descriptor parameters revealed that the highest dyeing strength was exhibited by dye 3, as indicated by the ELUMO, EHOMO, ∆E, S, and η parameters, while dye 6 had the highest dyeing strength based on the values of χ and µ parameters.

Design, Antimicrobial Testing, and Molecular Docking Studies of New Chalcone and Pyrimidine Derivatives based on 2-phenyl-1H-pyrazol-3(2H)-one

Background & Objectives: Heterocyclic pyrimidine and pyrazole rings have attracted the interest of medicinal chemists because of their pharmacological potential including antimicrobial activity. Based on molecular hybridization, new chalcones 6a-g and pyrimidines 7a-g based on a pyrazole scaffold were designed. Methods: The synthesis of these compounds involved mild condensation reactions between compound 4 and various aromatic aldehydes in a mixture of ethanol/NaOH (95:5 v/v) to give the corresponding chalcones 6a-g. These chalcones were further reacted with urea in the presence of a base in ethanol to produce the pyrimidine derivatives 7a-g. These new candidates were screened for their in vitro antimicrobial activities and molecular docking studies were evaluated. Results: The antibacterial and antifungal studies of all synthesized compounds against the strains tested showed that compounds 6c, d, and 7c, d exhibited the highest antibacterial and antifungal activities. In addition, the structure-activity relationship and docking studies are discussed. Conclusion: The synthesized compounds 6c, 6d, 7c, and 7d showed the highest antibacterial and antifungal activities against the tested strains.

Synthesis of sildenafil and its derivatives bearing pyrazolo‐pyrimidinones scaffold

AbstractThe pyrazole ring structure is extensively spotted as a pharmacophore and fortify‐cation of the modern organic synthesis toolbox, which demands synthetic tactics to generate its derivatives. Especially, pyrazolo‐pyrimidinones are crucial part to synthesize phosphodiesterase type 5 (PDE5) such as sildenafil and lodenafil. Herein, we report a simple and efficient route for Sildenafil and derivatives from easily available materials.

Metabolic characteristic profiling of 1-amino-3,3-dimethyl-1-oxobutan-2-yl-derived indole and indazole synthetic cannabinoids in vitro

Characterizing the metabolic profiles of synthetic cannabinoids (SCs), a type of new psychoactive substances, is of particular importance for forensic detection and analysis. Although the metabolism of individual SCs derived from 1-amino-3,3-dimethyl-1-oxobutan-2-yl (ADB-SCs) has been reported, their metabolites also undergo a continuous change and combination of their tail and core regions. Therefore, elucidating the metabolic characteristics and effects of these structures is essential to enhance our understanding. In this study, the human liver microsome was used as the model for studying the in vitro phase I metabolism of 12 ADB-SCs, and the metabolites obtained were analyzed using ultra-high performance liquid chromatography–tandem four-level rod-electrostatic field orbital ion trap mass spectrometry to determine type, structure, and relative contents. The results indicated that hydroxylation and N-dealkylation were the major metabolic pathways in 12 ADB-SCs. The effects of the core and tail on the metabolism of these ADB-SCs were studied using theoretical calculations. For N-dealkylation metabolism, the strong electron-withdrawing conjugative effect of the –N= moiety in the pyrazole ring, steric hindrance of the tail, and electronic effect of substituents on the tail significantly affected metabolism. Further, it changed the relative contents of N-dealkylation metabolites. For hydroxylation, the reaction types were inconsistent at different parts. For instance, the phenyl group of the core is electrophilic, and its electron cloud density determines whether the phenyl group can be hydroxylated at the specific metabolic sites. Meanwhile, hydroxylation of the neopentyl moiety of the linked group involves the oxidation of aliphatic C–H bonds, whereas amide–hydroxylamine tautomerism affects hydroxylation metabolism. When the alkyl chain in the tail contains functional groups (such as –F and >CC<), oxidative defluorination or dihydrodiol metabolites are produced. Taken together, we systematically determined d the effect of functional groups in the core and tail of ADB-SCs on their metabolism, validating confirmed the feasibility of ADB-SC metabolism prediction based on their structural characteristics.

Discovery of a potent, selective, and orally available EGFR C797S mutant inhibitor (DS06652923) with in vivo antitumor activity

The C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Herein, we describe the discovery of DS06652923, a novel, potent, and orally available EGFR-triple-mutant inhibitor. Through scaffold hopping from the previously reported nicotinamide derivative, a novel biaryl scaffold was obtained. The potency was successfully enhanced by the introduction of basic substituents based on analysis of the docking study results. In addition, the difluoromethoxy group on the pyrazole ring improved the kinase selectivity by inducing steric clash with the other kinases. The most optimized compound, DS06652923, achieved tumor regression in the Ba/F3 allograft model upon its oral administration.

Halogen bonding in 5-chloropyrazoles: Two new examples and a descriptive CSD investigation

This article presents an extensive Cambridge Structural Database (CSD) analysis on the presence and the role of the halogen bonds in the 5-chlorinated pyrazole motif. The study involved eighty CSD structures (83 .cif) and two new crystals of 1-aryl-5-chloropyrazoles obtained by us with the aim to establish the role of the chlorine atom attached at C-5 of the pyrazole ring both as donor and acceptor of the halogen bond. Different types of halogen contacts appear in 50 % of the investigated molecules. Chlorine atom in the 5-chloropyrazoles structures is involved in Cl···Cl, Cl···Y (Y: O, N, etc.), and Cl···π halogen contacts. The most numerous contacts found were of type Cl···Y (Y: O, N, etc.). The two new 1-aryl-5-chloropyrazole structures reported herein present Cl···O contacts at the sum of the vdW distance. The Cl···O contacts were evaluated also through DFT methods compared with other bonds acting on the same direction.