Chloranilic Acid Research Articles

Investigation of hydrogen bonds in proton transfer complexes derived from the reaction of 2- and 4-(N,N-dimethylamino)pyridines with chloranilic acid

New complexes of 2-(N,N-dimethylamino)pyridine with chloranilic acid (2-DMAP + CLA) and 4-(N,N-dimethylamino)pyridine with chloranilic acid (4-DMAP + CLA) were synthesized and characterized by single crystal X-ray diffraction, infrared spectroscopy, thermal analysis methods and 1H, 13C and 15N NMR spectroscopy. The NMR spectroscopies were carried out in both, DMSO solution and in the solid state (CPMAS NMR). The 2-DMAP + CLA and 4-DMAP + CLA complexes crystallize in centrosymmetric P-1 and P21/c space group, respectively.In both complexes, the phenomenon of proton transfer is observed, which results in the formation of strong N+–H···O– hydrogen bonds. Thermal decompositions of 2-DMAP + CLA and 4-DMAP + CLA complexes were studied by thermogravimetric analysis. Temperature dependent IR spectra revealed that methyl groups of 4-DMAP + CLA perform fast stochastic reorientational motion at room temperature which is slowed on cooling while in 2-DMAP + CLA reonrientational motion of CH3 groups is much slower due to steric effects.

Molecular crystals of 2-methyl-1H-benzo[d]imidazole and pyridine-2,6-dimethanol with chloranilic, trimesic and gallic acid

Crystallization experiments of 2-methyl-1H-benzo[d]imidazole (MBI) and pyridine-2,6- dimethanol (PDM) with chloranilic (CLA), trimesic (TMA) and gallic acid (GA) yielded a total of ten multicomponent molecular crystals in salt form, i.e., MBI:CLA (1), 2MBI:CLA:2H2O (2), 2MBI:CLA:3H2O (3A), 2MBI:CLA:3H2O (3B), 2MBI:CLA:4H2O (4), MBI:TMA (5), MBI:GA:3.4H2O (6), PDM:CLA (7), PDM:CLA:H2O (8), and 2PDM:CLA (9), of which compounds 3A and 3B are polymorphs. Characteristic for the crystal structures of all compounds except for 7 is the presence of heterosynthons formed between the molecular components by charge-assisted NHMBI/PDM⋯OCLA/TMA/GA hydrogen bonds, which are mostly bifurcated. In compound 7, the positively charged NH groups are involved in the formation of PDM-PDM homodimers interacting through NHPDM⋯OPDM hydrogen bonds. The series of compounds having 2:1 MBI/PDM:CLA ratio (2, 3A, 3B, 4 and 9) comprise trimeric molecular units of the composition MBI-CLA-MBI or PDM-CLA-PDM, respectively, based on charge-assisted bifurcated NH⋯O hydrogen bonds. Despite the directionality of these interactions, the units have certain flexibility consisting in mutual bending of the aromatic ring planes and are considered interesting building blocks for crystal engineering purposes. Except for compound 9, all crystal structures exhibit π⋯π interactions involving the positively charged benzimidazolium and pyridinium rings of protonated MBI and PDM and/or the π-delocalized sections in the organic anions. The water molecules in hydrates 2, 3A, 3B, 4, 6 and 8 exercise mostly crystal lattice stabilizing functions by interconnecting the synthons established among the organic components. Hirshfeld surface and fingerprint analysis revealed that O⋯H/H⋯O interactions and van der Waals contacts are dominant in conjunct with Cl⋯H/H⋯Cl contacts in the compounds derived from CLA.

Chloranilic acid–Gabapentin proton transfer complexes: Synthesis, spectroscopic, antimicrobial, computational, and molecular docking studies

The behavior of Gabapentin (Gab) towards Chloranilic acid (CLA) in solution is checked using UV–visible spectroscopy in three different solvents: methanol, ethanol, and acetonitrile. Applying Job's continuous variation method, the reaction is proved to proceed as a 1:1 molar composition in solution. On the other hand, two nanocrystalline solid products are isolated from the reaction of Gabapentin (Gab) with chloranilic acid (CLA), depending on the initial mole ratio (G1CLA and G2CLA). The isolated solid products are characterized by physicochemical tools (UV–vis., FT-IR, 1HNMR), proving the existence of proton transfer interaction. The semi-crystalline G2CLA (1CLA: 2Gab) product was investigated using powder x-ray diffraction, whereas the crystallized G1CLA (1CLA: 1Gab) product was analyzed by SXRD. The determined crystallite sizes for G1CLA and G2CLA were 30.02 nm and 40.17 nm, respectively. G1CLA was optimized in ethanol and gas phase, using DFT computational study, with basis sets B3LYP/6–31+G(d,p). The calculations showed the occurrence of charge transfer and hydrogen bonding in gas phase whereas proton transfer took place in ethanol. NBO charge calculations, reactivity parameters, and MEP maps indicated that CLA exhibits e-accepting ability, while Gab demonstrates e-donating properties. The main electronic transition states were determined by TD-DFT method. Moreover, the isolated solids were subjected to biological activity study, against six pathogens: two fungi, two gram-positive, and two gram-negative bacteria. Molecular docking simulation of G1CLA was performed on the crystal structure of proteus vulgaris HigA antitoxin (6CF1), revealing a total binding energy of -74.8704 Kcal/mole.

Green and High Throughput Assay Using 96-Microwell Base to Determine Metformin Hydrochloride in the Tablet Dosage Form.

Metformin (MET) is an oral antidiabetic drug widely used as the primary treatment for type 2 diabetes mellitus (T2DM). While various spectrophotometric assays exist for determining MET in pharmaceutical formulations, they often have limited throughput for quality control purposes. This study describes the validation of a 96-microwell plate spectrophotometer method using charge-transfer complexes (CTCs) with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for the quality control and detected of MET. This reaction was carried out in 96-microwell plates, and the absorbance of the colored complexes of CLA and DDQ were measured at 530 nm and 460 nm, respectively, using an absorbance microplate reader. This study aims to identify and quantify the use of a 96-microwell plate spectrophotometer analytical technique for assessing complicated formulations. The method was successfully used for the quantification of MET in the tablet dosage form. The results showed good correlation coefficients (0.996 and 0.997) with CLA and DDQ, respectively. The present method showed high precision with RSD % not exceeding 2.17%. The accuracy of the method was obtained by recovery percentage, with percentage values less than ±5%. The Analytical Greenness Metric (AGREE) was used to evaluate greenness of the assays. The result show that the microwell assay method is greenness and suitable for handling large samples on a daily used with high throughput analysis. The use of the 96-microwell-plate method is superior to the existing method in terms of simplicity of the procedure, the low economic cost, and its consumption of low amounts of reagents and organic ethanol solvent, making it an environmentally friendly method. Therefore, these advantages make them suitable and rapid alternatives method to current methods for routine metformin analysis in quality control laboratories.

Second coordination sphere modulation during water oxidation with metal-hydroxide organic frameworks

Kinetic isotope study, spectroscopic measurements, and electrochemical studies reveal the modulation of the first and second coordination sphere of the metal ions in active water oxidation catalysts with an appropriate ligand chloranilic acid.

Electrochemical water oxidation reaction by dinuclear Re(V) oxo complexes with a 1,4-benzoquinone core via the redox induced electron transfer (RIET) process.

We report two dinuclear rhenium(V) oxo complexes 1 and 2 types, [ReV(O)(Cl)3(L2-)ReV(O)(Cl)3][NBu4]2 (1, L2- = dianionic 2,5-dihydroxy 1,4-benzoquinone (DBQ2-)) and (2, L2- = dianionic chloranilic acid (CA2-) ligands), as a homogeneous electrocatalyst for water oxidation reactions in the acetonitrile-water mixture. The evolution of dioxygen gas at the anode was confirmed by a GC-TCD study. In controlled potential electrolysis (CPE), oxidation at 1.30 V (vs. Ag/AgCl) at neutral pH, 1 and 2 afforded 1+ [ReVI(O)(Cl)3(DBQ˙3-)ReVI(O)(Cl)3]- and 2+ [ReVI(O)(Cl)3(CA˙3-)ReVI(O)(Cl)3]- ions, respectively, via the redox induced electron transfer (RIET) process. Electrochemically generated species of 1+ and 2+ could be isolated in dry acetonitrile. 1+ and 2+ ions give strong EPR signals in fluid solution as well as under frozen glass conditions due to the [ReVI(O)(Cl)3(L˙3-)ReVI(O)(Cl)3]- ↔ [ReVI(O)(Cl)3(L2-)ReV(O)(Cl)3]- (where L2- = DBQ2- and CA2-) equilibrium. However, the continuation of the CPE study (1.30 V vs. Ag/AgCl) in the presence of acetonitrile-water mixture oxidised the in situ generated species of 1+ and 2+ to higher valent ReVIO species. These species (1+ and 2+) bound water through the water nucleophilic attack (WNA) to produce peroxide intermediate species of [ReV(OOH)(Cl)3(DBQ2-)ReV(OOH)(Cl)3] (A1) and [ReV(OOH)(Cl)3(CA2-)ReV(OOH)(Cl)3] (A2) for catalysts 1 and 2, respectively. Interestingly, A1 and A2 were authenticated and analysed by ESI mass spectrometry and infrared spectroscopy and were the active precursors of this water oxidation process. The extent of current generation under similar conditions suggested that complex 1 is superior to complex 2 for the water oxidation reaction. Notably, the maximum turnover frequency (TOFmax) of catalysts 1 and 2 were 2.1 and 1.6 s-1 at 0.27 V and 0.24 V over potential, respectively, which is very significant in WOR.

Spectrophotometric Study of Charge-Transfer Complexes of Ruxolitinib with Chloranilic Acid and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone: An Application to the Development of a Green and High-Throughput Microwell Method for Quantification of Ruxolitinib in Its Pharmaceutical Formulations

Ruxolitinib (RUX) is a potent drug that has been approved by the Food and Drug Administration for the treatment of myelofibrosis, polycythemia vera, and graft-versus-host disease. This study describes the formation of colored charge-transfer complexes (CTCs) of RUX, an electron donor, with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the π-electron acceptors. The CTCs were characterized using UV-visible spectrophotometry. The formation of CTCs in methanol was confirmed via formation of new absorption bands with maximum absorption at 530 and 470 nm for CTCs with CLA and DDQ, respectively. The molar absorptivity and other physicochemical and electronic properties of CTCs were determined. The molar ratio was found to be 1:1 for both CTCs with CLA and CTCs with DDQ. The site of interaction on RUX molecules was assigned and the mechanisms of the reactions were postulated. The reactions were employed as basis for the development of a novel green and one-step microwell spectrophotometric method (MW-SPM) for high-throughput quantitation of RUX. Reactions of RUX with CLA and DDQ were carried out in 96-well transparent plates, and the absorbances of the colored CTCs were measured by an absorbance microplate reader. The MW-SPM was validated according to the ICH guidelines. The limits of quantitation were 7.5 and 12.6 µg/mL for the methods involving reactions with CLA and DDQ, respectively. The method was applied with great reliability to the quantitation of RUX content in Jakavi® tablets and Opzelura® cream. The greenness of the MW-SPM was assessed by three different metric tools, and the results proved that the method fulfills the requirements of green analytical approaches. In addition, the one-step reactions and simultaneous handling of a large number of samples with micro-volumes using the proposed method enables the high-throughput analysis. In conclusion, this study describes the first MW-SPM, a valuable analytical tool for the quality control of pharmaceutical formulations of RUX.

Phosphine oxide donor-based dinuclear rhenium(I) metallocycles

Neutral binuclear metallocycles fac- [{Re(CO)3}2(CA)(L)] (1–2) were obtained using Re2(CO)10, flexible ditopic phosphine oxide donor 9,10-bis(dimethylphosphonomethyl)anthracene/ 9,10-bis(diethylphosphonomethyl)anthracene (L), and chloranilic acid (H2−CA) in mesitylene via one-pot solvothermal methods. The metallocycles were characterized by E.A., FT-IR, ESI-MS and NMR analysis. The solid-state structures of 1–2 were confirmed by X-ray analysis which reveal that the complexes adopt binuclear heteroleptic cyclic architectures. The fac- [Re(CO)3] core-based metallocycles 1–2 are two of the very few examples of phosphine oxide donor (P=O)-based supramolecular coordination cyclic complexes.

Charge Transfer Complex of Lorlatinib with Chloranilic Acid: Characterization and Application to the Development of a Novel 96-Microwell Spectrophotometric Assay with High Throughput.

Lorlatinib (LRL) is the first drug of the third generation of anaplastic lymphoma kinase (ALK) inhibitors used a first-line treatment of non-small cell lung cancer (NSCLC). This study describes, for the first time, the investigations for the formation of a charge transfer complex (CTC) between LRL, as electron donor, with chloranilic acid (CLA), as a π-electron acceptor. The CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational calculations. The UV-visible spectrophotometry ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 0.55 × 103 L mol-1 cm-1 and its band gap energy was 2.3465 eV. The stoichiometric ratio of LRL/CLA was found to be 1:2. The association constant of the complex was 0.40 × 103 L mol-1, and its standard free energy was -0.15 × 102 J mole-1. The computational calculation for the atomic charges of an energy minimized LRL molecule was conducted, the sites of interaction on the LRL molecule were assigned, and the mechanism of the reaction was postulated. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for LRL. The assay limits of detection and quantitation were 2.1 and 6.5 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of LRL in its bulk form and pharmaceutical formulation (tablets). This assay is simple, economic, and more importantly has a high-throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of LRL's bulk form and pharmaceutical tablets.

Heteroleptic Metal-Organic Frameworks of Lanthanides (Lа, Ce, and Ho) Based on Ligands of the Anilate Type and Dicarboxylic Acids

New heteroleptic metal-organic frameworks of lanthanides, units of which contain anionic organic ligands of two types, are prepared by the solvothermal synthesis in N,N-dimethylformamide (DMF). The cross-linked coordination polymer [Ho2(CA)2(Bdc)·4DMF] (I) and two scaffold derivatives [La2(pQ)2(Bpdc)·4DMF] (II) and [Ce2(CA)(Bdc)2·4DMF]·2DMF (III·2DMF), where CA is chloranilic acid dianion, pQ is 2,5-dihydroxy-3,6-di-tert-butyl-para-benzoquinone dianion, Bdc is terephthalic acid dianion, and Bpdc is 4,4'-biphenyldicarboxylic acid dianion, are synthesized. The structures of compounds I, II, and III·2DMF are studied by X-ray diffraction (XRD) (CIF file CCDC nos. 2212230, 2212231, and 2212232, respectively).

Microbiological and spectrophotometric methods for the determination of tioconazole: A comparative thermodynamic study

Two sensitive microbiological and charge transfer spectrophotometric methods have been developed for the quantitative determination of the antifungal drug, tioconazole, in its pure form and pharmaceutical preparations. The microbiological assay was based on the agar disk diffusion method by measuring the diameter of the inhibition zones related to different concentrations of tioconazole. The spectrophotometric method relied on charge transfer complex formation between tioconazole as an n-donor and chloranilic acid as a π-acceptor at room temperature. The formed complex was measured at λmax = 530 nm. The molar absorptivity and the formation constant of the formed complex were determined using different models, including the Benesi-Hildebrand, Foster-Hammick-Wardley, Scott, Pushkin-Varshney-Kamoonpuri, and Scatchard equations. Different thermodynamic parameters associated with the complex formation, including the free energy change (ΔG°), the standard enthalpy (ΔH°), and the standard entropy change (ΔS°), were evaluated. The two methods were validated in conformity with ICH-recommended guidelines and employed successfully for the quantification of tioconazole in both pure form and pharmaceutical formulations.

Indirect Flow Injection Spectrophotometric and Chromatographic Methods for the Determination of Mebendazole in Pharmaceutical Formulations

Chromatographic and spectrophotometric methods for the estimation of mebendazole in pharmaceutical products were developed. The flow injection method was based on the oxidation of mebendazole by a known excess of sodium hypochlorite at pH=9.5. The excess sodium hypochlorite is then reacted with chloranilic acid (CAA) to bleach out its color. The absorbance of the excess CAA was recorded at 530 nm. The method is fast, simple, selective, and sensitive. The chromatographic method was carried out on a Varian C18 column. The mobile phase was a mixture of acetonitrile (ACN), methanol (MeOH), water and triethylamine (TEA), (56% ACN, 20% MeOH, 23.5% H2O, 0.5% TEA, v/v), adjusted to pH = 3.0 with 1.0 M hydrochloric acid. Naphazoline nitrate was used as an internal standard. The absorption of mebendazole was measured using a variable wavelength UV detector at 290 nm. Linearity was obtained in the concentration range of 1-60 and 0.10-3.0 mg/L for the HPLC and FIA, respectively. The methods were applied successfully for the assay of mebendazole in pharmaceutical products and no interferences were observed from the common excipients usually used. The proposed methods were validated for their accuracy and precision.

Procainamide Charge Transfer Complexes with Chloranilic Acid and 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone: Experimental and Theoretical Study

The formation of charge transfer (CT) complexes between bioactive molecules and/or organic molecules is an important aspect in order to understand ‘molecule-receptor’ interactions. Here, we have synthesized two new CT complexes, procainamide-chloranilic acid (PA-ChA) and procainamide-2,3-dichloro-5,6-dicyano-1,4-benzoquinone (PA-DDQ), from electron donor procainamide (PA), electron acceptor chloranilic acid (ChA), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The structures of these two CT complexes were elucidated/characterized using FTIR, NMR, and many other spectroscopic methods. A stability study of each complex was conducted for the first time using various spectroscopic parameters (e.g., formation constant, molar extinction coefficient, ionization potential oscillator strength, dipole moment, and standard free energy). The formation of CT complexes in solution was confirmed by spectrophotometric determination. The molecular composition of each complex was determined using the spectrophotometric titration method and gave a 1:1 (donor:acceptor) ratio. In addition, the formation constant was determined using the Benesi–Hildebrand equation. To understand the noncovalent interactions of the complexes, density functional theory (DFT) calculations were performed using the ωB97XD/6-311++G(2d,p) level of theory. The DFT-computed interaction energies (ΔIEs) and the Gibbs free energies (ΔGs) were in the same order as observed experimentally. The DFT-calculated results strongly support our experimental results.

Exploring the photocatalytic activity of synthesized hydrogen bonded charge transfer co-crystal of chloranilic acid with 2-ethylimidazole: DFT, molecular docking and spectrophotometric studies in different solvents

An organic donor (2-ethylimidazole) and an organic acceptor (chloranilic acid) were used to investigate the charge transfer (CT) interaction in polar solvents. Initially, interaction occurs between the electron-rich donor and electron-deficient acceptor through the H-bonding [N+−H····O−], which ultimately results in the formation of CT complex. The CT complex was analyzed using elemental analysis, FTIR, SC-XRD, NMR, UV, and SEM. Based on the results obtained, we concluded that a weaker H-bond is responsible for CT complex formation. The molecular docking study revealed that the CT complex binds precisely and effectively to human serum protein with a free energy value of −8.2 kcal/mol−1. We have further demonstrated the utility of the synthesized complex as an efficient photo-catalyst to degrade methylene blue (MB) and 93% photo-degradation was achieved under UV irradiation for 120 min. Furthermore, the scavenging experiment was performed to determine the mechanism of photo-degradation, which showed the formation of h+ and O2−•as primary active species. DFT calculations using the B3LYP/6-311G++ level of theory were employed.

Synthesis, spectroscopic characterization, DNA binding and DFT/PCM calculations of new Hydrogen-bonded charge transfer complex between 4-dimethylaminopyridine and Chloranilic acid

A charge transfer hydrogen bonded complex between the electron donor 4-dimethylaminopyridine (4-DMAP) and the electron acceptor Chloranilic acid (CLA) has been synthesized. The complex was studied experimentally and theoretically. A chemical reaction developed due to strong H-bonding, followed by proton transfer from the CLA to the 4-DMAP in acetonitrile medium (ACN). The straight line approach was employed to verify the 1:1 M ratio of the synthesised CT complex. The Benesi-Hildebrand equation was employed to compute the association constant (KCT), molar absorptivity (εCT), and other physical parameters. The synthesized complex was characterized spectroscopically. The presence of proton and charge transfers in the resultant complex was supported by 1H NMR, FT-IR and SEM-EDX investigations. The complex DNA binding ability of complex was investigated using electron absorption spectroscopy to reveal that the CT complex binding mechanism is intercalative and the intrinsic binding constant (Kb) value is 6.7 × 104 M−1. Theoretical calculations using DFT at the basis set CAM-B3LYP/6–31 G (d, p) were used to validate the experimental outcomes. The Mullikan atomic charges, geometrical parameters, and molecular electrostatic potential maps (MEPs) were computed and interpreted in conformity with the experimental results. In addition to e-transfer, the presence of an H-bond influences complex stability. There is good agreement between experimental results and DFT calculations.

The Charge Transfer Complex between 2, 3-diamino-5-bromopyridine and Chloranilic acid: Preparation, Spectroscopic Characterization, DNA binding, and DFT/PCM analysis

A charge transfer hydrogen bonded complex was prepared and experimentally explored in an acetonitrile (ACN) medium between the proton acceptor (electron donor) 2, 3-Diamino-5-bromopyridine and the proton donor (electron acceptor) chloranilic acid. The stoichiometry of the charge transfer complex is 1:1. The Benesi-Hildebrand equation is used to calculate the molar absorptivity (εCT), association constant (KCT) and other spectroscopic physical characteristics. The solid compound was synthesized and studied using several spectroscopic methods. The presence of charge and proton transfers in the resultant complex was supported by 1H NMR, FT-IR and SEM-EDX investigations. The complex DNA binding ability was investigated using electron absorption spectroscopy, and the CT complex binding mechanism is intercalative. The intrinsic binding constant (Kb) value is 5.2 × 106M−1. The good binding affinity of the CT complex makes it potentially suitable for usage as a pharmaceutical in the future. Molecular docking calculations have been performed between CT complex and DNA (ID = 1BNA) to study the CT-DNA interaction theoretically. To corroborate the experimental findings, calculations based on DFT were carried out in the gas and PCM analysis where the existence of charge and hydrogen transfers. Finally, good agreement between experimental and theoretical computations was observed confirming that the basis set used is appropriate for the system under examination.

Supporting Electrolyte Manipulation for Simple Improvement of the Sensitivity of Trace Vanadium(V) Determination at a Lead-Coated Glassy Carbon Electrode.

The paper presents a very simple way to extremely improve the sensitivity of trace V(V) determination. The application of a new supporting electrolyte composition (CH3COONH4, CH3COOH, and NH4Cl) instead of the commonly used acetate buffer (CH3COONa and CH3COOH) significantly enhanced the adsorptive stripping voltammetric signal of vanadium(V) at the lead-coated glassy carbon electrode (GCE/PbF). A higher enhancement was attained in the presence of cupferron as a complexing agent (approximately 10 times V(V) signal amplification) than in the case of chloranilic acid and bromate ions (approximately 0.5 times V(V) signal amplification). Therefore, the adsorptive stripping voltammetric system with the accumulation of V(V)-cupferron complexes at -1.1 V for 15 s in the buffer solution (CH3COONH4, CH3COOH, and NH4Cl) of pH = 5.6 ± 0.1 was selected for the development of a simple and extremely sensitive V(V) analysis procedure. Under optimized conditions, the sensitivity of the procedure was 6.30 µA/nmol L-1. The cathodic peak current of V(V) was directly proportional to its concentration in the ranges of 1.0 × 10-11 to 2.0 × 10-10 mol L-1 and 2.0 × 10-10 to 1.0 × 10-8 mol L-1. Among the electrochemical procedures, the lowest detection limit (2.8 × 10-12 mol L-1) of V(V) was obtained for the shortest accumulation time (15 s). The high accuracy of the procedure was confirmed on the basis of the analysis of certified reference material (estuarine water) and river water samples.

Spectroscopic and Molecular Docking Analysis of π-Acceptor Complexes with the Drug Barbital

The drug barbital (Bar) has a strong sedative–hypnotic effect. The intermolecular charge transfer compounds associated with the chemical reactions between Bar and some π acceptors, such as 2,6-dibromoquinone-4-chloroimide (DBQ), tetracyanoquinodimethane (TCNQ), chloranil (CHL), and chloranilic acid (CLA), have been synthesized and isolated in solid state. The synthesized products have the molecular formulas (Bar–DBQ), (Bar–TCNQ), (Bar–CHL), and (Bar–CLA) with 1:1 stoichiometry based on Raman, IR, TG, 1H NMR, XRD, SEM, and UV-visible analysis techniques. Additionally, the comparative analysis of molecular docking between the donor reactant moiety, Bar, and its four CT complexes was conducted using two neurotransmitter receptors (dopamine and serotonin). The docking results obtained from AutoDockVina software were investigated by a molecular dynamics simulation technique with 100ns run. The molecular mechanisms behind receptor–ligand interactions were also looked into. The DFT computations were conducted using theory at the B3LYP/6-311G++ level. In addition, the HOMO LUMO electronic energy gap and the CT complex’s optimal geometry and molecule electrostatic potential were examined.

Synthesis, Single Crystal X-ray Structure, Spectroscopy and Substitution Behavior of Niobium(V) Complexes Activated by Chloranilate as Bidentate Ligand

Chloranilic acid (2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone, caH2) as a bidentate ligand for Nb(V) as a metal center is presented. The different coordination behavior of caH2 is well illustrated by a monomeric (Et4N)cis-[NbO(ca)2(H2O)OPPh3]·3H2O.THF (5) and a novel tetranuclear compound (Et4N)4[Nb4O4(ca)2(μ2-O)2Cl8]·2CH3CN (6) via self-assembly, respectively. These were obtained in >80% yields and characterized by IR, UV/Vis and NMR (1H, 13C{1H}, 31P{1H}) spectroscopy and single crystal X-ray diffraction, and they included a systematic assessment of the solid-state behavior. The anionic metal complexes showed different coordination modes at the Nb(V): [Nb4O4(ca)2(μ2-O)2Cl8]4− (6a; distorted octahedral) and cis-[NbO(ca)2(H2O)(OPPh3)]− (5a; D5h distorted pentagonal bipyramidal), respectively. The tetranuclear complex 6a is substitution inert, while cis-[NbO(ca)2(H2O)OPPh3]− (5a) allowed a systematic ligation kinetic evaluation. The substitution of the coordinated triphenylphosphine oxide by a range of pyridine-type entering nucleophiles, 4-N,N-dimethyl-aminopyridine (DMAP), pyridine (py), 4-methylpyridine (4Mepy), 3-chloropyridine (3Clpy) and 3-bromopyridine (3Brpy) in acetonitrile at 31.2 °C was carefully evaluated. The subtle interplay between the main group ligand systems and the hard, early transition metal Nb(V) complex (5a) was well illustrated. The entering monodentate ligands showed a 15-fold reactivity range increase in the order 3Brpy < 3Clpy < 4Mepy < py < DMAP in broad agreement with the Brønsted-donating ability of the nucleophiles. The activation parameters determined for the reaction of 5a with DMAP as the entering ligand yielded ΔH≠kf = 52 ± 1 kJ mol−1 and ΔS≠kf = −108 ± 3 J K−1 mol−1 for the enthalpy and entropy of activation, respectively, indicating an associative substitution mechanism. The study presents an important contribution to the structure/reactivity relationships in Nb(V) complexes stabilized by chloranilic acid as a bidentate ligand.

Thermodynamic and Computational (DFT) Study of Non-Covalent Interaction Mechanisms of Charge Transfer Complex of Linagliptin with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and Chloranilic acid (CHA).

This study describes the non-covalent interactions of the charge transfer complex (CT), which was responsible for the synthesis of Linagliptin (LNG) with 2,3-Dichloro-5,6-Dicyano-1,4-benzoquinone (DDQ), or with Chloranilic acid (CHA) complexes in acetonitrile (MeCN) at temperatures of (25 ± 2 °C). Then, a UV–Vis spectrophotometer was utilized to identify Linagliptin (LNG) from these complexes. For the quantitative measurement of Linagliptin in bulk form, UV–Vis techniques have been developed and validated in accordance with ICH criteria for several aspects, including selectivity, linearity, accuracy, precision, LOD, LOQ, and robustness. The optimization of the complex synthesis was based on solvent polarization; the ratio of molecules in complexes; the association constant; and Gibbs energy (ΔG°). The experimental work is supported by the computational investigation of the complexes utilizing density functional theory as well as (QTAIM); (NCI) index; and (RDG). According to the optimized conditions, Beer’s law was observed between 2.5–100 and 5–100 µM with correlation coefficients of 1.9997 and 1.9998 for LGN-DDQ and LGN-CHA complexes, respectively. For LGN-DDQ and LGN-CHA complexes, the LOD and LOQ were (1.0844 and 1.4406 μM) and (3.2861 and 4.3655 μM), respectively. The approach was successfully used to measure LGN in its bulk form with high precision and accuracy.