Chloro Derivatives Research Articles

A platform chemical from soybean hulls: Unveiling the bioactive effects of levoglucosenone derivatives

Soybean is one of the most extensively cultivated crops globally, and the soybean oil industry produces a significant amount of hulls annually. Utilizing this by-product to generate levoglucosenone through acid-catalyzed pyrolysis represents an environmentally friendly strategy to maximize the use of this crop and increase the value of the residue.This study explored the pyrolysis of soybean hulls to obtain the target enone and its application in the generation of new antifungal compounds. Halogenated derivatives were synthesized in a simple and straightforward manner and evaluated for antifungal activity against several Candida and Cryptococcus strains. Mechanistic studies investigated their interactions with ergosterol, impact on fungal cell wall synthesis, and inhibition of virulence factors. Biofilm formation assays were also conducted. Our results showed that the chloro derivative demonstrated the highest antifungal activity, exhibiting a remarkable minimum inhibitory concentration (MIC) and efficacy against both susceptible and resistant strains. It was also showed that the mode of action does not involve ergosterol bonding nor inhibition of cell wall synthesis. This study provides valuable insights into utilizing agricultural waste for developing bioactive compounds with pharmaceutical applications, contributing to the sustainable utilization of biomass resources in pharmaceutical research and development.

Mechanochemical oxidative complexation of copper(I) chloride with acetic acid, benzoic acid, their chloro derivatives and l-histidine affording anhydrous copper(II) complexes

This work reports solvent-free synthesis of copper(II)-carboxylates by grinding the reactants in solid state (the mechanochemical method). Here we used copper(I) salt to synthesize copper(II) complexes to demonstrate the potential of oxidative synthesis of the mechanochemical technique. The complexes were synthesized by grinding copper(I) chloride with a carboxylic acid together in 1:2 molar ratio in mortar and pestle. The carboxylic acids used were acetic acid, benzoic acid, 2-chloroacetic acid, 2-chlorobenzoic acid and l-histidine. The oxidative complexation occurred in the solid state producing anhydrous dimeric copper(II)-carboxylates (except that of l-histidine) in quantitative yield (>96%) having 1:2 metal to ligand ratio. The first evidence to oxidation of copper(I) to copper(II) ion was a change in color (pale to greenish blue) and a change in magnetic susceptibility from diamagnetic to paramagnetic value. The complexes were also characterized by elemental analysis, electronic absorption spectroscopy, FT-IR spectra, mass spectrometry, powder X-ray diffraction and thermal analysis. The electronic absorption, magnetic susceptibility, ESR and X-ray diffraction data supported a distorted square-planer geometry. This study provided for a distinct test in the form of magnetic susceptibility for the formation of copper(II)-complexes from a copper(I) salt. The dimeric nature of the complexes, except that of bis(histidinato)copper(II), was confirmed by the lower magnetic-moments (1.40–1.50 BM) than the spin only value (1.73 BM).

Correlation Between PFP, ERAS, PC-SAFT Models and Experimental Validation Through Thermodynamic and Spectroscopic Analysis of Acetonitrile with Chloro Derivatives of Ethane Binary Mixtures at Varying Temperatures

Correlation Between PFP, ERAS, PC-SAFT Models and Experimental Validation Through Thermodynamic and Spectroscopic Analysis of Acetonitrile with Chloro Derivatives of Ethane Binary Mixtures at Varying Temperatures

Dynamic features of virus protein 1 and substitutions in the 3-phenyl ring determine the potency and broad-spectrum activity of capsid-binding pyrazolo[3,4-d]pyrimidines against rhinoviruses

Pyrazolo[3,4-d]pyrimidines represent one potent class of well tolerated and highly active rhinovirus (RV) inhibitors that act as capsid binders. The lead compound OBR-5-340 inhibits a broad-spectrum of RVs. Aiming to improve lead activity, we evaluated the impact of structural modifications in the 3-phenyl ring of OBR-5-340 on its potency and spectrum of anti-RV activity vitro. Our results demonstrate the crucial role of substitution at position 4 for strong, broad-spectrum anti-RV activity. The 4-methyl (RCB23137) and 4-chloro (RCB23138) derivatives outperformed OBR-5-340 in terms of potency and anti-RV activity spectrum. Based on these findings, the compounds were selected for computational binding studies. Molecular dynamic simulations with six RVs differing in OBR-5-340, RCB23137, and RCB23138 sensitivity proved the impact of dynamic features of two VP1 loops enveloping these inhibitors on antiviral potency.

Developments of Pyrrolo[2,3-d]pyrimidines with Pharmaceutical Potential

: In terms of fused heterocyclic compounds, pyrrolopyrimidines, and their substituted analogs are among the most extensively explored scaffolds. Based on the location of the nitrogen atom in the pyrrole ring, pyrrolopyrimidines have different isomers. This study deals only with the pyrrolo[2,3-d]pyrimidine isomer. Several techniques are represented and discussed in this review for producing pyrrolo[2,3-d]pyrimidine derivatives. The first one is the cyclization of the pyrimidine ring on the pyrrole ring through the reaction of β-enaminonitrile, β-enaminoester or β-enaminoamide of the pyrrole ring with different bifunctional reagents such as formic acid, acetic acid, acetic anhydride, formamide, isothiocyanate, urea, thiourea, and carbon disulfide. The second technique includes cyclization of the pyrrole ring on the pyrimidine ring via the treatment of pyrimidine, aminopyrimidine, diamino-pyrimidine, or triamino-pyrimidine with different reagents such as nitroalkenes, alkynes, aldehydes, and acid chlorides. In addition, different reaction methodologies like one pot, two-step, and threestep synthetic methodologies were reported. The last technique for producing pyrrolo[2,3-d]pyrimidine derivatives is through miscellaneous reactions. This review also includes the interactions of pyrrolo[2,3- d]pyrimidines at different active centers of the pyrrole ring with different reagents to form N-alkylated, Nglycosylated, C-5, and C-6 adducts. Besides, the interactions on the pyrimidine ring to form chloro, hydrazino, and amino-imino derivatives were also discussed. The amino-imino derivatives are key intermediates for the preparation of tricyclic pyrrolotriazolopyrimidines. Finally, the pharmaceutical and biological properties of some pyrrolo[2,3-d]pyrimidine derivatives have also been mentioned. This information can be utilized to design novel diverse pyrrolopyrimidine derivatives for recent challenges in pharmaceutical and medical studies to develop the already existing drugs or discover new ones.

Lewis Acid-Mediated Isothiocyanation and Chlorination of Quinoxalin-2(1H)-ones under Visible Light Conditions.

Lewis acid-mediated selective C3-isothiocyanation of quinoxalin-2(1H)-ones using N-thiocyanatosaccharin as an isothiocyanate source under visible light conditions at room temperature is described. Under similar conditions with N-chlorosaccharin, the C3-chlorination of quinoxalin-2(1H)-ones achieved a 2 h time frame. Good to an excellent yield of products was obtained in both cases with broad functional group tolerance. Control experiments suggest that the reaction proceeds through a radical mechanism. The present procedure demonstrates the applicability at gram-scale reactions and highlights the subsequent conversion of isothiocyanates into representative thiourea derivatives, and one of the chloro derivatives transformed to glycogen phosphorylase inhibitors.

Green Fluorescence Property of Chromone-based Hydrazone Towards Zn2+ Ion

Excessive concentration of Zn in the environment may lead to bad toxicological responses that can affect human health and create numerous challenges in the environment. Therefore, it is very important to develop a sensitive method such as selective chemosensors based on fluorescence property which does not require laborious work in order to detect Zn metal ion. A formylchromone-thiosemicarbazide with two chloro derivatives namely DFCTSC was synthesized from reflux reaction of 6,8-dichloroformylchromone (DCF) and thiosemicarbazide (TSC) in ethanol. The characterisation of ligand structure was determined by using spectroscopic techniques such as Fourier transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-VIS) and nuclear magnetic resonance spectroscopy (NMR). Meanwhile, the fluorescence property of DFCTSC in the presence of Zn ion was recorded using fluorescence spectrophotometer. The result showed DFCTSC has a good fluorescence behaviour towards Zn ion by giving turn-on green fluorescence at peak 500 nm and emit light when it observed under UV light. The behaviour displayed the ability of ligand to be used as a potential fluorescent chemosensor for detecting Zn2+.

Hydrazone-flavonol based oxidovanadium(V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo

Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1H and proton-decoupled 13C(1H) NMR spectroscopy, alongside extensive 2D 1H1H COSY, 1H13C HMQC, and 1H13C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6–31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents.

Modeling of experimental excess molar enthalpy with Wilson, UNIQUAC, and NRTL for mixtures of acetophenone with chloro derivatives of ethane and ethene at T = 298.15 K

The excess molar enthalpy HmE, was determined for systems consisting of acetophenone with chloro alkanes and alkenes derivatives. These derivatives include 1,2-dichloroethane, 1,1,1-trichloroethane, 1,1,2,2-tetrachloroethane, trichloroethene and tetrachloroethene at a temperature of T = 298.15 K. The Redlich-Kister relation fitting was used to analyze the HmE values obtained from this experimental data. Additionally, the excess partial molar enthalpy HiE was derived from the experimental HmE values. The intermolecular interaction function such as ∂HiE∂xi and ∂HjE∂xjwere also calculated. For the system consisting of acetophenone + 1,1,1-trichloroethane or + tetrachloroethene, the HmE values were found to be positive. Conversely, the HmE values for acetophenone + 1,2-dichloroethane or + 1,1,2,2- tetrachloroethane or + trichloroethene were observed to be negative. The magnitude of the HmE values increased in chloroethanes as the number of chlorine atoms increased, and became more negative in chloroethenes. Based on the local composition theory, the Wilson model, the universal quasichemical (UNIQUAC) model, and the non-random two-liquid (NRTL) model were used to correlate these thermodynamic data. The results showed good agreement with the experimental enthalpy data.

Structure and Chiroptical Properties of Anthra[1,2-a]anthracene-1-yl Dimers as New Biaryls.

Dimers of anthra[1,2-a]anthracene-1-yl units and its mesityl derivative were synthesized by Ni(0)-mediated coupling of the corresponding chloro derivatives as new biaryls. The X-ray analysis and DFT calculations revealed that two polycyclic aromatic units with nonplanar deformations took a twisted conformation about the single bond as a chiral axis. Enantiomers of the nonsubstituted compound were resolved by chiral HPLC, and the enantiopure samples showed intense Cotton effects at 321 nm in the circular dichroism (CD) spectra and emission bands at 449 nm in the circularly polarized luminescence (CPL) spectra with dissymmetry factor of |glum| 3.6×10-3. The absolute stereochemistry of this biaryl was determined by the theoretical calculation of CD spectrum by the time-dependent DFT method. The barrier to enantiomerization was determined to be 108 kJ mol-1 at 298 K. The dynamic process proceeded via a stepwise mechanism involving the helical inversion of each aromatic unit and the rotation about the biaryl axis as analyzed by the DFT calculations.

Trans-Di-bromido-tetra-kis-(5-methyl-1H-pyrazole-κN2)manganese(II).

The title compound, trans-di-bromido-tetra-kis-(5-methyl-1H-pyrazole-κN 2)manganese(II), [MnBr2(C4H6N2)4] or [Mn(3-MePzH)4Br2] (1) crystallizes in the triclinic P space group with the cell parameters a = 7.6288 (3), b = 8.7530 (4), c = 9.3794 (4) Å and α = 90.707 (4), β = 106.138 (4), γ = 114.285 (5)°, V = 542.62 (5) Å3, T = 120 K. The asymmetric unit contains only half the mol-ecule with the manganese atom is situated on a crystallographic inversion center. The 3-MePzH ligands are present in an AABB type manner with two methyl groups pointing up and the other two down. The supra-molecular architecture is characterized by several inter-molecular C-H⋯N, N-H⋯Br, and C-H⋯π inter-actions. Earlier, a polymorphic structure of [Mn(3-MePzH)4Br2] (2) with a similar geometry and also an AABB arrangement for the pyrazole ligands was described [Reedijk et al. (1971 ▸). Inorg. Chem. 10, 2594-2599; a = 8.802 (6), b = 9.695 (5), c = 7.613 (8) Å and α = 105.12 (4), β = 114.98 (4), γ = 92.90 (3)°, V = 558.826 (5) Å3, T = 295 K]. A varying supra-molecular pattern was reported, with the structure of 1 featuring a herringbone type pattern while that of structure 2 shows a pillared network type of arrangement along the a axis. A nickel complex [Ni(3-MePzH)4Br2] isomorphic to 1 and the analogous chloro derivatives of FeII, CoII and CuII are also known.

In silico Design, Synthesis and Biological Evaluation of Novel Thieno[3,2-d]pyrimidine Derivatives for Cancer Therapy - A Preliminary Study on the Inhibitory Potential towards ATR Kinase Domain and PIKK Family.

Continuing our studies in the field of new heterocyclic compounds with biological interest, herein we report the synthesis and anticancer activity of new N- and S-substituted derivatives of tetracyclic pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines. In this regard, starting from the thieno[2,3-b]pyridine-2-carboxylates, the corresponding 8(9)-aminopyrido[3',2' : 4,5]thieno[3,2-d]pyrimidin-7(8)-ones, as well as chloro derivatives were obtained. Based on the latter, amino, hydrazino and S-alkyl derivatives of pyrido[3',2' : 4,5]thieno[3,2-d]pyrimidines were synthesized subsequently. The current study focuses on identifying the potential of thieno[3,2-d]pyrimidine derivatives primarily towards ATR kinase inhibition, through computational predictions, followed by synthesis and cancer cell viability studies, along with an aim to develop the core as PIKK inhibitors for cancer therapy.

Synthesis and evaluation of 2-phenylamino-1,4-naphthoquinones derivatives as potential hypoglycaemic agents.

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Synthesis of new fused 3(4)-substituted 11-furylthieno[3,2-<i>d</i>]pyrimidine derivatives

A method was developed for the synthesis of new fused 3-alkyl-substituted derivatives of thieno[3,2- d ]pyrimidin-4(3 H )-ones based on 11-(2-furyl)-8,8-dimethyl-7,10-dihydro-8 H -pyrano[3′′,4′′:5′,6′]pyrido[3′,2′:4,5]-thieno[3,2- d ]pyrimidin-4(3 H )-one via nucleophilic substitution in the pyrimidine ring. A series of fused 4-amino-substituted 11-furylthieno[3,2- d ]pyrimidine derivatives was also synthesized from the corresponding 4-chloro derivative.

AMINATION OF 2-(2-OXO-2-ARYLETHYLTHIO)-PYRIMIDIN-4(3H)-ONE DERIVATIVES USING THE SULFONATE METHOD

A Derivatives of 2-thiouracil are characteri­zed by wide spectrum of biological activity, which is characteristic of most representatives this heterocycles class. In particular, 2-(2-oxo-2-phenylethylthio)-pyrimi­din-4(3H)-ones belong to the group of non-nucleoside inhibitors of HIV-1 reverse transcriptase. The antimalarial properties of 2-(2-oxo-2-phenylethyl­thio)-4-R-pyrimidine derivatives, which proved to be effective inhibitors of CIpP protease of Plasmodium falciparum, are being studied. Known examples of 2-(2-oxo-2-phenylethyl­thio)-pyrimidines modification at the "4" position of the heterocycle are limited to use 4-chloro derivatives, which, in turn, are formed according to the classical method by reaction of pyrimidine-4(3H)-ones with POCl3 at boiling point of reaction mixture. In this work, we present an alternative version of modification the above-mentioned class of compounds. By amination amide function of 6-R-2-(2-oxo-2-arylethylthio)-pyrimidin-4(3H)-ones derivati­ves of with ethanolamine and 1-aminopropa­ne-2,3-diol using sulfonate method, synthesized and characterized new compounds a 6-R-2-(2-oxo-2-phenylethylthio)-pyrimidines series by spectral methods. The advantages of this scheme are discussed (the formation of intermediate sulfonates and the amination stage do not require harsh conditions and are carried out with satisfactory yields). The proposed scheme can be recommended in cases where the original substrate contains functio­nal groups that are labile at high temperatures and sensitive to an acidic environment.

Challenging breast cancer through novel sulfonamide-pyridine hybrids: design, synthesis, carbonic anhydrase IX inhibition and induction of apoptosis.

Background: Among the important key modulators of the tumor microenvironment and hypoxia is a family of enzymes named carbonic anhydrases. Herein, 11 novel sulfonamide-pyridine hybrids (2-12) were designed, synthesized and biologically evaluated for their potential use in targeting breast cancer. Methods & results: The para chloro derivative 7 reported the highest cytotoxic activity against the three breast cancer cell lines used. In addition, compound 7 was found to induce cell cycle arrest and autophagy as well as delaying wound healing. The IC50 of compound 7 against carbonic anhydrase IX was 253±12nM using dorzolamide HCl as control. Conclusion: This study encourages us to expand the designed library, where more sulfonamide derivatives would be synthesized and studied for their structure-activity relationships.

Anti-inflammatory and Analgesic Studies of 2-aryl-3-(5-alkyl-1, 3, 4-thiadiazol-2-yl) 4-thiazolidinones

Any damage and bad stimulus causes pain and inflammation. The compound used for pain is known as analgesic and for inflammation is known as anti-inflammatory. The title compounds were evaluated for analgesic activity using Tail-Flick method and anti-inflammatory activity using Carrgenan Induced Rat Paw Edema. Diclofenac Sodium used as standard drug. The chloro, fluro and nitro containg derivatives showed best activity as compared to methyl, methoxy and hydroxy derivatives.

Fused-Pentagon Carbon Cages in Chloro and Trifluoromethyl Derivatives of C60: Non-IPR 1809C60Cl8, 1806C60(CF3)14, and Nonclassical C60(NC)Cl14.

High-temperature chlorination of conventional IPR C60 can produce chloro derivatives of non-IPR C60 by skeletal transformations via Stone-Wales rearrangements (SWRs) of the carbon cage. We report the synthesis and structure elucidation of non-IPR 1809C60Cl8 and nonclassical C60(NC)Cl14. The present isolation of 1809C60Cl8 hints at the possibility that the same product in the previously reported chlorine-doped arc-discharge synthesis could have, likewise, resulted from the initially formed IPR C60. C60(NC)Cl14 is the first chloride containing a nonclassical carbon cage with one heptagon and 13 pentagons known previously only in a CF3 derivative. Additionally, trifluoromethylation of non-IPR chlorides revealed the formation of 1806C60(CF3)14 with a new non-IPR carbon cage and unusual trifluoromethylation pattern. Thereby, the number of different, structurally confirmed non-IPR carbon cages of C60 now reaches eight.

Preparation and crystal structure of C84(11)Cl20,22, chloro derivatives of a C84 minor isomer

Chlorofullerenes C84(11)Cl20 and C84(11)Cl22 were prepared by chlorination of C2–C84(11) with VCl4 at 340–360 °C. An X-ray crystallographic study with the use of synchrotron radiation revealed the chlorination patterns featuring only para additions in C6Cl2 hexagons.

Synthesis, DFT, and photophysical studies of substituted pyridine carbonitrile derivatives

The synthesis and photophysical study of cyanopyridine derivatives of chalcones are very fascinating because of their excellent fluorescent nature in solid and solution states. Their emission properties accomplish the need for fluorescent probes for optoelectronic applications. Herein we synthesized the cyanopyridine derivative PC (1-3) by hetero cyclization of chalcone using malononitrile. The structure was confirmed by spectroscopic (NMR, FTIR, and, Mass) and DFT data. The solid-state emission showed the emission in the UV region (250-400 nm) for PC1 and PC2. The PC3 showed feeble emission both in solid and solution states. The corresponding chloro and thiophene derivatives showed good emission intensity because of Intramolecular Charge Transfer (ICT) enhancement. The Commission Internationale de l'Elcairage (CIE) color coordinates showed blue emission in the solution state. The emission maxima were centered at 391, 385, and 487 nm for PC1, PC2, and PC3 respectively. There are two absorption bands in the range of 265-309 nm and 323-379 nm due to π-π* and n-π* transitions. The synthesized molecules have shown broad and high solid-state emission with good fluorescence quantum efficiency and these attributes have been extensively leveraged in the fabrication of optical sensors, imaging substances, and organic light-emitting diodes.