2D Fingerprint Research Articles

Prediction of molecular field points using SE(3)-transformer model

Due to their computational efficiency, 2D fingerprints are typically used in similarity-based high-content screening. The interaction of a ligand with its target protein, however, relies on its physicochemical interactions in 3D space. Thus, ligands with different 2D scaffolds can bind to the same protein if these ligands share similar interaction patterns. Molecular fields can represent those interaction profiles. For efficiency, the extrema of those molecular fields, named field points, are used to quantify the ligand similarity in 3D. The calculation of field points involves the evaluation of the interaction energy between the ligand and a small probe shifted on a fine grid representing the molecular surface. These calculations are computationally prohibitive for large datasets of ligands, making field point representations of molecules intractable for high-content screening. Here, we overcome this roadblock by one-shot prediction of field points using generative neural networks based on the molecular structure alone. Field points are predicted by training an SE(3)-Transformer, an equivariant, attention-based graph neural network architecture, on a large set of ligands with field point data. Resulting data demonstrates the feasibility of this approach to precisely generate negative, positive and hydrophobic field points within 0.5 Å of the ground truth for a diverse set of drug-like molecules.

Structural investigation, quantum chemical calculation, energy framework analysis and MIC studies of silver and cobalt complexes of 4-amino-N-(4, 6-dimethyl-2 pyrimidinyl) benzenesulfonamide in presence of secondary ligand

Silver and cobalt complexes of SMZ ligand (SMZ = 4-amino-N-(4, 6-dimethyl-2 pyrimidinyl) benzenesulfonamide) have been synthesized and characterized by elemental, FT-IR and 1H-NMR spectroscopy analysis. Due to the magnetic behaviour of the cobalt complex, it was characterized by EPR and magnetic susceptibility analysis. Single crystal X-ray diffraction (SC-XRD) study reveals the [Ag2(C12H14N4O2S)2(C6H7N), complex-1 crystallizes in orthorhombic space group Pbca, while [{Co(C12H13N4O2S)2(C5H5N)2}.(C5H5N)], complex-2 crystallizes in monoclinic space group C2/c. The SC-XRD analysis shows that silver in complex-1 is four-coordinate exhibiting distorted tetrahedral geometry, while cobalt in complex-2 is coordinated to six nitrogen’s leading to distorted octahedral geometry. Additionally, Hirshfeld surfaces and 2D fingerprint plots analysis shows that the H…H intermolecular contacts are the main contribution to the Hirshfeld surface area displaying values for complex-1 and complex-2 are 59.1% and 50% respectively (%H-H; complex 1 > Complex 2). In 3D energy frameworks analysis, complex-1, has shown the highest dispersion interaction energies than that of complex 2 [dispersion energy; -74.5 kJ mol-1 (complex-1) > -63.4 kJ mol-1 (complex-2)], Moreover, computational studies such as frontier molecular orbital (FMO), natural bond orbital (NBO) and Mulliken population analysis (MPA) were calculated using B3LYP method. Besides, The MIC data against panel of gram-positive and gram-negative organisms confirm that both the metal complexes of SMZ ligand possesses better inhibitory activities than that of SMZ ligand. The MIC data shows the silver complex exhibits comparatively better response towards the panel of the gram positive and gram negative bacteria. Furthermore, the molecular docking study agrees that the binding affinity of the complexes with 1BNA is higher than that of free SMZ ligand.

Experimental and Theoretical Biological Probing of Schiff Bases as Esterase Inhibitors: Structural, Spectral and Molecular Insights.

The present study was designed to evaluate the in vitro and in silico potential of the Schiff bases (Z)-4-ethoxy-N-((5-nitrothiophen-2-yl)methylene)benzenamine (1) and (Z)-2,4-diiodo-6-((2-methyl-3-nitrophenylimino)methyl)phenol (2). These Schiff bases were synthesized according to a reported method using ethanol as a solvent, and each reaction was monitored on a TLC until completion of the reaction. The structures of both compounds were elucidated using spectroscopic techniques such as UV-Vis, FTIR, 1H NMR and 13C NMR. Molecular structure was determined using single-crystal XRD, which revealed that compounds 1 and 2 were monoclinic and triclinic, respectively. Hirshfeld surface analysis (HS) and 2D fingerprint plots were used to determine the intermolecular interactions along the contact contribution in the crystalline molecules. The structures of both compounds were optimized through a hybrid functional method B3LYP using the 6-31G(d,p) basis set, and various structural parameters were studied. The experimental and theoretical parameters (bond angle and bond length) of the compounds were compared with each other and are in close agreement. The in vitro esterase potential of the synthesized compounds was checked using a spectrophotometric model, while in silico molecular docking studies were performed with AutoDock against two enzymes of the esterase family. The docking studies and the in vitro assessment predicted that such molecules could be used as enzyme inhibitors against the tested enzymes: acetylcholine esterase (AChE) and butyrylcholine esterase (BChE).

Structural elucidation and spectroscopic studies of acetyl substituted piperazine nucleus tethered with 4, 5-diaryl-1 H-imidazole scaffold: DNA binding, Cu2+and Sn2+ ions sensing and cytotoxicity

In this study, we report on synthesis of new imidazole based fluorescentchemosensors2-((4-(5-bromo-2-hydroxy-3-(4,5-diphenyl-1H-imidazol-2-yl)benzyl)piperazine-1-yl)methyl)-4-bromo-6-(4,5-diphenyl-1H-imidazole-2-yl)phenol(1)and2-((4-(2-hydroxy-5-methyl-3-(4,5-diphenyl-1H-imidazol-2-yl)piperazine-1-yl)methyl)-4-methyl-6-(4,5-diphenyl-1H-imidazole-2-yl)phenol(2). The synthesized chemosensors 1 and 2 were characterized by FT-IR, 1H NMR, UV–visible and fluorescence spectral studies. Further, the single crystal X-ray diffraction analysis shows that the chemosensor 1 crystallizes in triclinic system, with space group P-1.Hirshfeld surface analysis and 2D fingerprint maps revealed that 1 have remarkable H…H, C…H/H…C, and O…H/H…O Br…H/H…Br, interactions. The chemosensors have developed for selective and sensitive detection of Sn2+ and Cu2+ions in methanol among other tested cation. A bathochromic shift and color change with respect to the intra-molecular charge transfer transition in the absorption spectra was displayed after the addition of Sn2+ and Cu2+ions. The “Turn-on” fluorescence enhancement to Sn2+ ions and “turn-off” fluorescence quenching response to Cu2+ ions at λmax 450 and 448 nm, respectively, were detected in the fluorescence emission spectra of 1 and 2 upon addition of Sn2+ and Cu2+ions⁻. The receptor senses Sn2+ and Cu2+ ions via the deprotonation of the phenolic O-H unit, which was further confirmed by 1H NMR titration. Moreover, the fluorescence imaging in A549 cells suggested that chemosensors had great potential in the application of bio-imaging. The chemosensors1 and 2 with Sn2+ ions were found to be cytotoxic against A549 cells andthe IC50 of 1 and 2 have value of 107.40 μM and 8.21 μM, respectively and could be used as an anticancer agent.

Structural analysis and properties of three novel sulfonic acid-based pharmaceutical salts of paliperidone

Three novel paliperidone sulfonate salts, including salt 1 (paliperidone methanesulfate), salt 2 (paliperidone benzenesulfate), and salt 3 (paliperidone p-toluenesulfate), were successfully designed and synthesized using a slow solvent evaporation method. Through TGA-DSC (thermogravimetric analysis-differential scanning calorimetry) testing, it was observed that the decomposition temperatures of these newly developed pharmaceutical salts were increased by 90 K, highlighting their enhanced thermal stability compared with paliperidone. The formation of these salts was primarily attributed to intermolecular hydrogen bonding interactions, as revealed by single-crystal structure analyses. Furthermore, the analyses of 3D dnorm Hirshfeld surface and 2D fingerprint plots demonstrated that the molecular stability was further enhanced by the interactions of H···H and H···O. Salt 1 showed a 10-fold increase in solubility and an approximately 200-fold increase in dissolution rate in a variety of simulated human body fluid environments. The confirmation of the formation of paliperidone drug salts and the high purity of the synthesized salts were further supported by PXRD (powder X-ray diffraction) and IR (infrared spectroscopy) analysis. Notably, this study represents the first reported investigation of paliperidone sulfonate salts, potentially providing valuable insights for the improvement of paliperidone pharmaceutical formulations.

AndroPred: an artificial intelligence-based model for predicting androgen receptor inhibitors

Androgen receptor (AR), a steroid receptor, plays a pivotal role in the pathogenesis of prostate cancer (PCa). AR controls the transcription of genes that help cells avoid apoptosis and proliferate, thereby contributing to the development of PCa. Understanding AR molecular mechanisms has led to the development of newer drugs that inhibit androgen production enzymes or block ARs. The FDA has approved a small number of AR-inhibiting drugs for use in PCa thus far, as the identification of novel AR inhibitors is difficult, expensive, time-consuming, and labor-intensive. To accelerate the process, artificial intelligence (AI) algorithms were employed to predict AR inhibitors using a dataset of 2242 compounds. Four machine learning (ML) and deep learning (DL) algorithms were used to train different prediction models based on molecular descriptors (1D, 2D, and molecular fingerprints). The DL-based prediction model outperformed the other trained models with accuracies of 92.18% and 93.05% on the training and test datasets, respectively. Our findings highlight the potential of DL, particularly the DNN model, as an effective approach for predicting AR inhibitors, which could significantly streamline the process of identifying novel AR inhibitors in PCa drug discovery. Further validation of these models using experimental assays and prospective testing of newly designed compounds would be valuable to confirm their predictive power and applicability in practical drug discovery settings. Communicated by Ramaswamy H. Sarma

Fingerprint Systems: Sensors, Image Acquisition, Interoperability and Challenges.

The fingerprint is a widely adopted biometric trait in forensic and civil applications. Fingerprint biometric systems have been investigated using contact prints and latent and contactless images which range from low to high resolution. While the imaging techniques are advancing with sensor variations, the input fingerprint images also vary. A general fingerprint recognition pipeline consists of a sensor module to acquire images, followed by feature representation, matching and decision modules. In the sensor module, the image quality of the biometric traits significantly affects the biometric system's accuracy and performance. Imaging modality, such as contact and contactless, plays a key role in poor image quality, and therefore, paying attention to imaging modality is important to obtain better performance. Further, underlying physical principles and the working of the sensor can lead to their own forms of distortions during acquisition. There are certain challenges in each module of the fingerprint recognition pipeline, particularly sensors, image acquisition and feature representation. Present reviews in fingerprint systems only analyze the imaging techniques in fingerprint sensing that have existed for a decade. However, the latest emerging trends and recent advances in fingerprint sensing, image acquisition and their challenges have been left behind. Since the present reviews are either obsolete or restricted to a particular subset of the fingerprint systems, this work comprehensively analyzes the state of the art in the field of contact-based, contactless 2D and 3D fingerprint systems and their challenges in the aspects of sensors, image acquisition and interoperability. It outlines the open issues and challenges encountered in fingerprint systems, such as fingerprint performance, environmental factors, acceptability and interoperability, and alternate directions are proposed for a better fingerprint system.

1-D MOF [Ag2(C10H10N3O3S)2(C4H8N)2]n: photocatalytic treatment, crystallographic evaluation, ADMET parameters, CT-DNA and anticancer activity

Newly synthesized dinuclear crystalline polymer, the silver complex of bidentate Sulfamethoxazole (Ag-SMX) in the presence of secondary ligand pyrrolidine has been characterized by elemental, spectral (1H-NMR spectra, FT-IR spectra, UV–Vis spectra.), powder XRD, and single-crystal X-ray diffraction (single-crystal) analysis. The synthesis molecular structure of the dinuclear [Ag2(C10H10N3O3S)2(C4H8N)2]n complex reveals a one-dimensional polymeric chain with seesaw geometry (τ4 = 0.71): two silvers interlink each other by argentophilic interaction with Ag1…Ag2 separation distance of 3.0047(6) Å. The Hirshfeld surfaces (HS) and 2D fingerprint plots were used to examine the interconnects in the crystal packing. Molecule properties including MEP, MPA, HOMO-LUMO energy, and global reactivity descriptor parameters were computed to understand the molecule’s stability. From ADMET parameters, human Intestinal Absorbance data revealed that the compound has the potential to be well absorbed, and also Ag-smx complex cannot cross the blood-brain barrier (BBB). The capacity of the silver complex to interact with CtDNA was investigated using absorption spectroscopy and viscosity tests. The interaction between CT-DNA reveals that the Ag-SMX complex exhibits the strongest binding affinity among all known sulfonamide derivatives and their metal complexes. The silver complex has higher inhibitory action than the free SMX ligand, according to data from a panel of gram (+ve) and gram (-ve) organisms’ minimum inhibitory concentrations. In vitro cytotoxicity investigation revealed that the IC50 value for Ag-SMX is 57.12 g/mL and for SMX is 100.90 g/mL against human lung cancer cell line (A549). This study revealed that, when compared to SMX free-ligand, Ag-SMX is the most effective in terms of cytotoxicity toward the human lung cancer cell line (A549 cell line). In under 120 min, the synthesized Ag-smx complex showed exceptional photo-degradation characteristics against methylene blue (MB) (10 ppm) in visible light radiation. Communicated by Ramaswamy H. Sarma

The supramolecular hybrid inorganic–organic l-argininato-based copper(II) materials – preparation, structural, spectroscopic and thermal properties

Synthesis and characterization of the single crystal of new ternary copper(II) complexes containing l−arginine of formulae {[Cu(μ−O,O’−NO3)(l−Arg)(bpy)]NO3}n (1) and [CuCl(l−Arg)(bpy)]Cl·3H2O (2) (l−Arg =l−arginine; bpy=2,2′−bipyridine) with one−dimensional polymeric and monomeric nature, respectively, were the initial goal of the present study. Complete crystal and molecular structures figuration were achieved by powder and single crystal X−ray diffraction supported by Hirshfeld surface analysis, spectroscopic (FT−IR, FT−Raman, X− and Q−bands EPR, NIR−Vis−UV) methods as well as thermal analysis. In 1, the infinite 1D coordination chains are formed by the NO3– ions linking [Cu(l−Arg)(bpy)]2+ units. In 2, the self−assembled [Cu(l-Arg)(bpy)Cl]+ dimers are linked into 1D zig-zag chains. The intermolecular interactions in both crystals were explored by using Hirshfeld surface and 2D fingerprint plots analysis. The Q−band spectra displayed the anisotropic signals allowing to determine the g|| parameters. The thermal decomposition of complexes 1 and 2 occur by the formation of “creatine−proline” as a product of l−Arg decomposition.

Exploring the Crystal Structure Landscape of Sulfasalazine through Various Multicomponent Crystals.

Sulfasalazine is used as an anti-inflammatory drug to treat large intestine diseases and atrophic arthritis. In the solid state, two tautomers are known: an amide tautomer (triclinic polymorph) and an imide tautomer (monoclinic polymorph). Crystallization of six new multicomponent solids of sulfasalazine with three cocrystal formers and three salt formers has been achieved by slurry, liquid-assisted grinding and slow evaporation methods. All of the solid forms are characterized by X-ray diffraction techniques, thermal analysis, and Fourier transform infrared spectroscopy. The crystal structural analysis reveals that two sulfasalazine molecules or anions arrange in a head-to-head fashion involving their pyridyl, amide, and sulfonyl groups in an R22(7):R22(8):R22(7) motif. This is the key structural unit appearing in both sulfasalazine imide polymorph and all six multicomponent crystals. In addition, sulfasalazine exists in the amide form in all unsolvated multicomponent crystals obtained in this work and adopts the imide tautomer in the solvated cocrystals and salt. Hirshfeld surface analysis and the associated two-dimensional (2D) fingerprint plots demonstrate that sulfasalazine has significant hydrogen bond donor capability when cocrystallized and is a significant hydrogen bond acceptor in the salts. The frontier molecular orbital analysis indicates that sulfasalazine cocrystals are chemically more stable than the salts.

Recent Advances in Machine-Learning-Based Chemoinformatics: A Comprehensive Review.

In modern drug discovery, the combination of chemoinformatics and quantitative structure-activity relationship (QSAR) modeling has emerged as a formidable alliance, enabling researchers to harness the vast potential of machine learning (ML) techniques for predictive molecular design and analysis. This review delves into the fundamental aspects of chemoinformatics, elucidating the intricate nature of chemical data and the crucial role of molecular descriptors in unveiling the underlying molecular properties. Molecular descriptors, including 2D fingerprints and topological indices, in conjunction with the structure-activity relationships (SARs), are pivotal in unlocking the pathway to small-molecule drug discovery. Technical intricacies of developing robust ML-QSAR models, including feature selection, model validation, and performance evaluation, are discussed herewith. Various ML algorithms, such as regression analysis and support vector machines, are showcased in the text for their ability to predict and comprehend the relationships between molecular structures and biological activities. This review serves as a comprehensive guide for researchers, providing an understanding of the synergy between chemoinformatics, QSAR, and ML. Due to embracing these cutting-edge technologies, predictive molecular analysis holds promise for expediting the discovery of novel therapeutic agents in the pharmaceutical sciences.

Crystal Design, Antitumor Activity and Molecular Docking of Novel Palladium(II) and Gold(III) Complexes with a Thiosemicarbazone Ligand.

The current research describes the synthesis and characterization of 2-acetylpyridine N(4)-cyclohexyl-thiosemicarbazone ligand (HL) and their two metal complexes, [Au(L)Cl][AuCl2] (1) and [Pd(L)Cl]·DMF (2). The molecular structures of the compounds were determined by physicochemical and spectroscopic methods. Single crystal X-ray diffraction was employed in the structural elucidation of the new complexes. The complexes showed a square planar geometry to the metal center Au(III) and Pd(II), coordinated with a thiosemicarbazone molecule by the NNS-donor system and a chloride ion. Complex (1) also shows the [AuCl2]- counter-ion in the asymmetric unit, and complex (2) has one DMF solvent molecule. These molecules play a key role in the formation of supramolecular structures due to different interactions. Noncovalent interactions were investigated through the 3D Hirshfeld surface by the dnorm function and the 2D fingerprint plots. The biological activity of the compounds was evaluated in vitro against the human glioma U251 cells. The cytotoxicity results revealed great antitumor activity in complex (1) compared with complex (2) and the free ligand. Molecular docking simulations were used to predict interactions and properties with selected proteins and DNA of the synthesized compounds.

A novel centrosymmetric [C7H9NF]2ZnCl4 hybrid material: Synthesis, crystal structure, thermal, vibrational spectroscopy, optical and photoluminescence properties

A novel organic–inorganic hybrid material, [C7H9NF]2ZnCl4, was obtained by slow evaporation at room temperature and characterized by single crystal X-ray diffraction. The compound has monoclinic space group P21/n with the following cell parameters: a= 15.1956(10) Å, b= 7.2108(3) Å, c = 36.103(2) Å, β=93.16°, V=3950.1 Å3 and Z=8. The crystal structure consists of tetrahedral [ZnCl4]2− anions and 4-fluorobenzylammonuim [C7H9NF]+ cations connected by hydrogen bonding N–H…Cl, C–H…Cl, π-π, and van der Waals interactions, which ensures the stability of the crystal packing, forming layers lying approximately within the (101) planes. RT- XPRD was carried out to identify the purity of the synthesis material. Infrared spectroscopy technique is used to characterize the vibrational properties of the system. The material exhibits thermal stability up to 180 °C. Hirshfeld surface analysis reveals the significance of hydrogen bonds and electrostatic interactions in the material cohesion, while 2D fingerprint plots indicate the contributions of the H…Cl and H…H intermolecular interactions. The material also displays diffuse absorption, indicating the existence of optical direct allowed transition mechanisms with the band gap energy equal to 4.33 eV. Its photoluminescence spectrum extends over the entire visible band when excited by ultraviolet radiation. Owing to these properties, the compound is promising for use in optical devices.

Theoretical insight on the optical centred electrical properties of guanidinium isophthalate NLO crystal for electro-optic Q switches

Guanidinium isophthalate single crystals with dimensions 16 × 4 x 2 mm3 were prepared by the low temperature solvent evaporation method and growth kinetics with interfacial tension was discussed to bring out the growth parameters of guanidinium isophthalate single crystals. The harvested single crystals were utilized for various characterization studies like powder X-ray diffraction, optical transmission, photoluminescence, laser damage study and optical limiting studies. The visualization of varying potential regions on the surfaces to quantify short contacts were generated by Hirshfeld surface analysis. 2D fingerprint plots were analyzed, in which H ….H contact was found to be the most significant with 54.1%. Growth kinetics of the crystalline material was studied to reveal the nucleation process. Crystal samples prepared with reference to the solubility data were found to be free of inclusions and cracks and had maximum transmittance in the complete visible region. The electronic disorder of the crystal sample was reported in the form of Urbach energy. The PL spectra with the emission intensity provide the emission characteristic of the title compound. The major fundamental optical limit for a crystal material is experimentally measured and presented in the picosecond regime. Thus the present work contributes to the understanding of growth, structural, optical and electronic characteristics of the title guanidinium isophthalate single crystals for the fabrication of electro-optic devices in photonic industry.

Monocular 3D Fingerprint Reconstruction and Unwarping.

Compared with contact-based fingerprint acquisition techniques, contactless acquisition has the advantages of less skin distortion, more complete fingerprint area, and hygienic acquisition. However, perspective distortion is a challenge in contactless fingerprint recognition, which changes the ridge frequency and relative minutiae location, and thus degrades the recognition accuracy. We propose a learning-based shape-from-texture algorithm to reconstruct a 3-D finger shape from a single image and unwarp the raw image to suppress the perspective distortion. Our experimental results for 3-D reconstruction on contactless fingerprint databases show that the proposed method has high 3-D reconstruction accuracy. Experimental results for contactless-to-contactless and contactless-to-contact-based fingerprint matching indicate that the proposed method can improve the matching accuracy.

Synthesis, experimental and theoretical (DFT) analysis, molecular docking and ADME properties of (E)-N'-(3-ethoxy-4-hydroxybenzylidene)isonicotinohydrazide (3E4HBINH)

Synthesis and characterisation like single crystal X-ray crystallography, FT-IR, DFT, MEP, UV–Vis, molecular docking and ADME properties of (E)-N'-(3-ethoxy-4-hydroxybenzylidene)isonicotinohydrazide (3E4HBINH) were reported here. The structure of 3E4HBINH is belongs to monoclinic system with space group P21/c. According to small molecule docking studies with the target protein, 3E4HBINH is a small molecule that interacts well with the Complex of the catalytic part of human HMG-CoA reductase. The calculated vibrational frequencies (Fourier Transfroms –Infrared & Fourier Transforms -Raman spectrum) of 3E4HBINH molcule is compared and it shows good agreement with experimental values. The molecular electrostatic potential (MEP) facilitates the enhancement of protein-ligand electrostatic interactions. The chemical surface and hydrogen bonding interactions in the 3E4HBINH crystal structure were identified and studied using a 2D fingerprint plot and Hirshfeld Surfaces. The optimized geometry like bond length and bond angle of the 3E4HBINH molecule is calculated using Density functional Theory (DFT)-B3LYP calculations using 6–31++G (d, p) basis set, and the observed bond lengths and bond angles are shows good agreement with experimental XRD values. Using preADMET online server, the characteristics of absorption, distribution, metabolism, and excretion (ADME) were examined.

Two novel metal complexes based on 2,2′-bipyridine and 2,4-dihydroxybenzoic acid: Synthesis, crystal structure and catalytic performance

To further enhance the catalytic performance of copper/lead 2,4-dihydroxybenzoate salt, two novel ternary complexes, Cu(C10H8N2)2(C7H5O4)·3H2O (complex 1) and [Pb(C10H8N2)(C7H5O4)2]·H2O (complex 2) were designed by introducing carbon framework ligand. The molecular structures of complexes 1 and 2 were determined by single crystal X-ray diffraction analysis. Both complex 1 and complex 2 were crystallized in the monoclinic crystal system. The difference is that the central Cu ion in complex 1 is connected to one oxygen atom of the carboxyl group of 2,4-dihydroxybenzoic acid, while the other 2,4-dihydroxybenzoic acid anion only acts as a counterion to balance the charge. But the central Pb ion in complex 2 is connected to four oxygen atoms of the carboxyl groups of two 2,4-dihydroxybenzoic acid and forms a six-coordinated structure. The Hirshfeld surface and associated 2D fingerprint analysis offer valuable insights into the intermolecular interactions within the crystal structure. Importantly, the thermal analysis results show that the thermal decomposition temperature of complex 1 is 204.1 °C, which has better thermal stability than complex 2. Furthermore, complex 1 showed remarkable catalytic activity on RDX compared to complex 2, and changed the thermal decomposition of RDX from melting decomposition to solid phase decomposition. This study will provide a new insight into development of combustion catalysts.

Monobromination of 2-hydroxy-6-methoxyacetophenone and studies of the non-covalent interactions in the crystal structure of 3-bromo-2-hydroxy-6-methoxyacetophenone

In principle both position C-3 and C-5 of 2-hydroxy-6-methoxyacetophenone (1) should be able to react with N-bromosuccinimide (NBS), being jointly activated by the meta directing effect of the carbonyl group and strongly so by the ortho-para directing resonance effects of the hydroxyl and methoxy group, respectively. However, this acetophenone derivative reacted with NBS in acetic acid to afford 3-bromo-2-hydroxy-6-methoxyacetophenone (2), exclusively. Intramolecular hydrogen (CO…HO) bonding interaction in ortho-hydroxycarbonyl compounds result in a thermodynamically stable six-membered ring with the resultant complex resembling naphthalene. C-3 becomes the α-position of this naphthaneloid scaffold and therefore the most activated/nucleophilic for electrophilic attack by NBS. The molecular electrostatic potential (MEP) map of substrate 1 shows that C-3 accommodates higher negative charge than that on C-5 making the former centre more susceptible to electrophilic attack. Moreover, density functional theory (DFT) method also predicted the 3-Br isomer to be more stable and favoured than the 5-Br form in acetic acid solution and also in the gas phase. Single crystals of the monobrominated acetophenone 2 were obtained and the structure of this compound was accurately established with the aid of X-ray diffraction technique complemented with spectroscopic (NMR, FT-IR, Uv-Vis and HR-MS) and DFT methods. The intermolecular interaction pattern was studied by Hirshfeld surface analysis along with 2D fingerprint diagrams. The DFT calculations were also performed in the gas phase to correlate the experimental results with the simulated data.

Structure determination through powder X-ray diffraction, Hirshfeld surface analysis, and DFT studies of 2- and 4-(methylthio)benzoic acid

Abstract 2-(methylthio)benzoic acid (1) is an ortho-substituted benzoic acid derivative, whereas 4-(methylthio)benzoic acid (2) is a para-substituted benzoic acid derivative. The structural analysis of both compounds was carried out using PXRD data. 2-(methylthio)benzoic acid shows a triclinic system with the P 1 ‾ $P\overline{1}$ space group, whereas 4-(methylthio)benzoic acid shows a monoclinic system and crystallizes in the P21/a space group. The strength, as well as relative contributions of intermolecular hydrogen bonds, have been examined through Hirshfeld surfaces as well as 2D fingerprint plots. A weak intramolecular hydrogen bond was found only in the case of ortho-substituted 2-(methylthio)benzoic acid. Supramolecular frameworks for 1 are formed by the interplay of intramolecular and intermolecular interactions, whereas for 2, intermolecular contacts form supramolecular assemblies. Intermolecular O–H⋯O interactions involving carboxyl groups form the R2 2(8) graph-set motif for both compounds. Theoretical DFT calculations using the B3LYP correlation functional reveal that the energy gap of HOMO–LUMO orbitals in compound 1, with the methylthio moiety in the ortho position relative to the carboxyl group, is lower than that of compound 2, with the methylthio moiety in the para position. Vertical and adiabatic ionization energies are also calculated for both compounds.

A Probe to Surface Reactivity, Crystal Structure, and DFT Investigations for Newly Synthesized 4,5-bis(4-Nitrophenyl)-8a-phenyl-decahydro-[1,3]diazino[4,5-d]pyrimidine-2,7-dione: A Combined Theoretical and Experimental Study

The multicomponent reaction of 4-nitrobenzaldehyde with acetophenone and urea in the presence of HCl was investigated, and, as a result, 4,5-bis(4-nitrophenyl)-8a-phenyl-decahydro-[1,3]diazino[4,5-d]pyrimidine-2,7-dione was synthesized. The structure of the synthesized compound was confirmed by the X-ray method. We performed Hirshfeld surfaces (HS) analysis and two-dimensional (2D) fingerprint plots for the studied compound to obtain surface reactivity and intermolecular interactions. The H∙∙∙H interactions were found to be higher, up to 32.2%, while the percentage C∙∙∙O contact was found to be the lowest among the reported interactions for single crystal packing. The energy framework analysis shows the strength of interaction energy within fragments of a single crystal at 3.08 A distances. The DFT study shows structural reactivity and a reduced HOMO-LUMO gap up to 4.0 eV. The NPA study reveals the reactivity and excellent charge transfer within the structure. The TD-DFT study reveals the absorbance in the UV region and excited state parameters during crucial transitions (transitions with maximum oscillator strength). The investigated compound shows excellent optical and nonlinear optical (NLO) properties, as indicated by its polarizability (αo) and hyperpolarizability (βo) values.