Effect of geometric isomerism on the anticancer property of new platinum complexes with glycine derivatives as asymmetric N, O donate ligands against human cancer.

In this project, to fallow the anticancer ability of new Pt drugs, several new Pt complexes were synthesized with the asymmetric bidentate glycine derivatives, as named propyl- and hexyl glycine (L), in the general formula: [Pt(NH3)2(L)]NO3, and cis- and trans-[Pt(L)2]. The structure of two cis- and trans-[Pt(propylgly)2] complexes was proved by single crystallography analysis. However, all complex structures were characterized by various methods of 1H NMR, 13C NMR, 195Pt NMR, FTIR, LC-Mass, and Raman spectroscopy. To study the passage of water-soluble complexes of [Pt(NH3)2(L)]NO3 via cell membrane, their solubility, and lipophilicity were analyzed. In addition, the cytotoxic properties of these complexes were evaluated against normal and malignant cell lines (skin, breast, and lung cancer cells). The results indicated that they were either comparable to cisplatin or less damaging than carboplatin and oxaliplatin. It was expected that due to less steric effect, and the presence of length aliphatic hydrocarbon chain in the complex structure, trans-[Pt(hexylgly)2] is more toxic on cancerous cell lines than trans-[Pt(propylgly)2]. Cellular accumulation of all complexes was evaluated on A549 and MCF7 cell lines, and the amount of platinum metal (ng) was measured by the ICP method. Results showed that trans-[Pt(hexylgly)2] complex has the highest accumulation inside both mentioned cell lines and [Pt(NH3)2(L)]NO3 complexes behave like clinical Pt-drugs. Ultimately, the interaction patterns of DNA were examined using spectroscopic methods and molecular docking simulations for all substances.

Sulfur- and DABCO-Promoted Reaction between Alkylidene Rhodanines and Isothiocyanates: Access to Aminoalkylidene Rhodanines.

In this work, an efficient sulfur- and DABCO-promoted reaction for the synthesis of aminoalkylidene rhodanines from available alkylidene rhodanines and isothiocyanates is reported. A tandem process including sulfurative annulation/ring-opening by liberation of a CS2 molecule/olefination allows the synthesis of aminoalkylidene rhodanines with acceptable functional group tolerance. Chemo- and stereoselectivity, operational simplicity, and synthetically useful yields are some highlighted advantages of these transformations.

Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands.

To investigate the structure and bioactivity relationship, six Pd(II)/Pt(II) complexes with N-isobutylglycine (L1) and cyclohexylglycine (L2) as N^O amino acid bidentate ligands, 1,10'-phenanthroline (phen) and 2,2'-bipyridine (bipy) as N^N donor ligands, and [Pd(L1)(bipy)]NO3 (1), [Pd(L2)(bipy)]NO3 (2), [Pd(L1)(phen)]NO3 (3), [Pd(L2)(phen)]NO3·2H2O (4), [Pt(L1)(phen)]NO3 (5), along with [Pt(L2)(phen)]NO3 (6) were prepared and then characterized. The geometry of each compound was validated by doing a DFT calculation. Furthermore, tests were conducted on the complexes' water solubilities and lipophilicity. All bipy complexes had superior aqueous solubility and less lipophilicity in comparison with phen complexes, as well as complexes containing cyclohexyl-glycine compared to isobutyl-glycine complexes, probably because of the steric effects and polarity of cyclohexylglycine. The in-vitro anticancer activities of these compounds were examined against HCT116, A549, and MCF7 cancerous cell lines. Data revealed that all Pd/Pt complexes demonstrate higher anticancer activity than carboplatin, and complexes 3 and 4 are more cytotoxic than cisplatin against the HCT116 cell line, particularly against MCF7 cancerous cells. In addition, among all compounds, complex 4 has more anticancer ability than oxaliplatin. Due to different solubility and lipophilicity behavior, the accumulation of Pt complexes and clinical Pt drugs in each cancerous cell was investigated. The binding capabilities of these complexes to DNA, as the main target in chemotherapy, occur through minor grooves and intercalate into DNA, which was done using absorption, fluorescence, and circular dichroism spectroscopy. Finally, the docking simulation study showed the mode of DNA bindings is in good agreement with the spectral binding data.

Three-Component Reaction between 3-Acetylcoumarins, Amines, and Elemental Sulfur: A Designed Approach to 3-Amino-4H-thieno[3,2-c]coumarins.

In this work, a series of novel 3-amino-4H-thieno[3,2-c]coumarins were designed and synthesized by a one-pot, catalyst-free, and three-component reaction of 3-acetylcoumarins with amines and elemental sulfur. Readily available starting materials, simple heating conditions, facile installation of a sulfur atom into the molecule using S8 as a sulfur source, acceptable functional group tolerance, and synthetically useful yields are some highlighted benefits of this process.

Efficient synthesis of novel thiadiazolo[2,3-b]quinazolin-6-ones catalyzed by diphenhydramine hydrochloride-CoCl⋠6H2O deep eutectic solvent.

In this research, a new Lewis acid-based deep eutectic solvent (LA-DES) was synthesized using diphenhydramine hydrochloride and CoCl2·6H2O, (2[HDPH]:CoCl42-), and identified by FT-IR and 1HNMR techniques. The physicochemical properties of this LA-DES, such as thermal behavior, thermal stability, and solubility in common solvents were also investigated. The catalytic ability of 2[HDPH]:CoCl42- was ascertained in the efficient synthesis of a novel array of thiadiazolo[2,3-b]quinazolin-6-one scaffolds via a one-pot three-component reaction of dimedone/1,3-cyclohexanedione, aldehydes, and 5-aryl-1,3,4-thiadiazol-2-amines/3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one under solvent-free conditions. This catalyst was also successfully utilized for the synthesis of mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehydes or bis-1,3,4-thiadiazol-2-amine. The simplicity of enforcement, short reaction time, avoidance of toxic organic solvents, scalability of the synthesis procedure, excellent atom economy, high reaction mass efficiency, and low E-factor are other outstanding advantages of this newly developed method. Furthermore, due to the convenient recovery and reuse of LA-DES, this protocol is economically justified and environmentally friendly.

In Situ Conversion of Ligand to a Coordination Polymer via a Core@Shell Crystal: A Multi-Step Phase-Dependent Structural Transformation.

Two pseudopolymorphic 1D coordination polymers of the formulas [Cd(3,3'-pytz)(CH3OH)2(ClO4)2]n (1) and [Cd(3,3'-pytz)(CH3CN)2(ClO4)2]n (2) have been prepared using the electron-deficient 3,6-bis(pyridin-3-yl)-1,2,4,5-tetrazine (3,3'-pytz) ligand and cadmium perchlorate in the chloroform/methanol and chloroform/acetonitrile solvent system, respectively. It was observed that compounds 1 and 2 experienced one-step (CPreagent → CPproduct) single-crystal-to-powder structural transformation to the pure water-coordinated compound [Cd(3,3'-pytz)(H2O)2(ClO4)2]n (3) by absorbing water vapor from air (solid-gas phase transformation). Interestingly, compounds 1, 2, and 3 undergo a different transformation path and show an in situ unique three-step (CPreagent → CPproduct → Ligandintermediate → CPproduct) single-crystal-to-single-crystal (SCSC) structural transformation process through soaking in deionized water (solid-liquid phase transformation). In this fascinating transformation, we report for the first time the direct conversion of a ligand into a coordination polymer by a rare core-shell pathway in a solid-liquid phase transformation. In this process, we obtained compound {[Cd(3,3'-pytz)(H2O)4](3,3'-pytz)2(ClO4)2(H2O)6}n (4) (single-crystal = S, crystal = C, or microcrystal = P) as mixed compounds of core-shell L@4C and 4S or core-shell L@4P and 4P for compounds (1 and 2) and 3, respectively.

Using Triazolobenzodiazepine as the Cyclic Imine in Various Types of Joullié-Ugi Reactions.

The triazolobenzodiazepine as a cyclic imine was employed in a variety of Joullié-Ugi reactions, and three new families of unique triazolobenzodiazepine connected to carboxamide and tetrazole products were synthesized via a three-component reaction of the cyclic imine and isocyanides with each species of a carboxylic acid/water/TMSN3 under mild conditions in high yields. Furthermore, triazolobenzodiazepine imine was used in an interesting strategy based on the modified Ugi reaction (pseudo-Joullié-Ugi reaction) of cyclic imines with an isocyanide and acetylenedicarboxylates under catalyst-free conditions for the synthesis of triazolobenzodiazepine-fused pyrroles. Mechanistic investigation reveals that triazolobenzodiazepine-fused pyrroles have been generated via a surprising route. Significantly, the use of triazolobenzodiazepine in the Joullié-Ugi, azido-Joullié-Ugi, and pseudo-Joullié-Ugi reactions of a broad scope of biological scaffolds occurred under mild, simple conditions without any catalyst.

The new synthesis of pyrrole-fused dibenzo[b,f][1,4]oxazepine/thiazepines by the pseudo-Joullié-Ugi reaction via an unexpected route with high chemoselectivity.

A novel and unexpected route for synthesizing pyrrole-fused dibenzoxazepines/thiazepines has been designed based on a modified Ugi reaction of cyclic imines with isocyanides and acetylenedicarboxylates under catalyst-free conditions. Mechanism investigation indicates that this process is carried out through the production of zwitterion species (Huisgen's 1,4-dipole), which is a key intermediate in the chemoselectivity of products. This Huisgen's 1,4-dipole is trapped in situ with isocyanides and a variety of pyrrole-fused dibenzoxazepines/thiazepines are synthesized in a simple one-pot operation with high yields and chemoselectivity. This strategy opens a new route in Ugi reactions (pseudo-Joullié-Ugi reaction) for the synthesis of pyrrole-fused heterocycles as special pharmaceutical scaffolds.

Diphenhydramine Hydrochloride-CuCl as a New Catalyst for the Synthesis of Tetrahydrocinnolin-5(1H)-ones.

The current study deals with the synthesis and characterization of a novel catalyst made from diphenhydramine hydrochloride and CuCl ([HDPH]Cl-CuCl). The prepared catalyst was thoroughly characterized using various techniques, such as 1H NMR, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis and derivative thermogravimetry. More importantly, the observed hydrogen bond between the components was proven experimentally. The activity of this catalyst was checked in the preparation of some new derivatives of tetrahydrocinnolin-5(1H)-ones via a multicomponent reaction between dimedone, aromatic aldehydes, and aryl/alkyl hydrazines in ethanol as a green solvent. Also, for the first time, this new homogeneous catalytic system was effectively used for the preparation of unsymmetric tetrahydrocinnolin-5(1H)-one derivatives as well as mono- and bis-tetrahydrocinnolin-5(1H)-ones from two different aryl aldehydes and dialdehydes, respectively. The effectiveness of this catalyst was further confirmed by the preparation of compounds containing both tetrahydrocinnolin-5(1H)-one and benzimidazole moieties from dialdehydes. The one-pot operation, mild conditions, rapid reaction, and high atom economy, along with the recyclability and reusability of the catalyst, are other notable features of this approach.

Water Content-Controlled Formation and Transformation of Concomitant Pseudopolymorph Coordination Polymers.

Two concomitant pseudopolymorph coordination polymers {[Cd2L2(OAc)4]·2DMSO} n (1) and {[CdL(OAc)2]·2.75H2O} n (2) were synthesized by self-assembly of 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene (L) and cadmium acetate in DMSO. Single-crystal X-ray diffraction confirmed that 1D ladder structural motifs exist for pseudopolymorphs 1 and 2 which contain DMSO and water guest molecules, respectively. Our study illustrated the active role of solvent water content in obtaining compound 2. We find that the presence of water as an impurity in the DMSO solvent creates the possibility of formation of concomitant pseudopolymorph coordination polymers which is a unique event. Furthermore, our analyses showed the effect of environmental humidity on the transformation of unstable compound 1. 1D ladder pseudopolymorphic compound 1 could be transformed to guest-free 1D linear compound [CdL(OAc)2(H2O)] n (3') (the powder form of single crystals of 3) through a scarce case of water absorption from air. Also, the crystalline material of coordination polymer 3 was transformed to coordination polymer 2 through the dissolution-recrystallization structural transformation process in DMF or DMSO. Our study clarified that the amount of water in the reaction container can control the formation of one of the compounds 2 or 3. In the presence of a significant amount of water, compound 3 (coordinated water) will be produced, whereas if a small amount of water is present, compound 2 (uncoordinated water) is prepared as an exclusive product.

Substrate-Controlled Diastereo- and Enantiodivergent Synthesis of Bis-Spirocyclopropyloxindoles from Available Isatin as a Single Starting Material.

The first diastereo- and enantiodivergent asymmetric synthesis of new bis-spirocyclopropyloxindole scaffolds has been accomplished from the readily available isatin as a single starting material. Four rel-(1R,2R,3R), rel-(1S,2S,3R), rel-(1R,2R,3S), and rel-(1S,2S,3S) configurations of desired products were constructed in excellent enantiopurity via a simple switch in substrates using the chiral auxiliary-controlled method. The absolute configuration of cycloadducts with three contiguous quaternary/tertiary stereogenic centers was confirmed through X-ray diffraction analysis. A facile synthesis of versatile precursor 3-chlorooxindoles was also introduced.

Biocatalytic stereoselective synthesis of pyrrolidine-2,3-diones containing all-carbon quaternary stereocenters.

Highly functionalized pyrrolidine-2,3-diones can be synthesized efficiently and stereoselectively under mild conditions using a biocatalytic approach. The reaction led to the formation of new all-carbon quaternary stereocenters from Myceliophthora thermophila laccase (Novozym 51003) catalyzed oxidation of catechols to ortho-quinones and subsequent 1,4-addition with 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones. The reaction was conducted with various substituents on both reactants, resulting in 13 products in moderate to good yields (42-91%). The same 15 reactions were also tested with K3Fe(CN)6 as a catalyst, but here only one reaction resulted in a product (60% yield).

Regioselective synthesis of enantiopure 1,2- and 1,3-dispirooxindoles along with a DFT study.

In the present study, a library of important enantiopure dispirooxindole [indolizidine, pyrrolizidine, and pyrrolidine] derivatives with three or four contiguous and two quaternary stereogenic centers using different amino acids (pipecolic acid, sarcosine, proline and hydroxyproline) were synthesized in high yields (up to 96%) through a regio- and diastereoselective (up to 99 : 1) multicomponent 1,3-dipolar cycloaddition strategy. Based on the results, the alteration of amino acids led to a change in the regioselectivity and unusual regioisomers (pyrrolizidine versus indolizidine/pyrrolidine) were obtained to construct a novel enantiopure 1,3-dispirooxindole skeleton. The stereochemical outcome of the cycloaddition was determined by single crystal X-ray diffraction analysis and the self-disproportionation of enantiomers (SDE) test confirmed the enantiomeric purity of the desired products. The mechanism and differences in the regioselectivity of the 1,3-dipolar cycloaddition reactions between the stable azomethane ylides obtained from ninhydrin, pipecolinic acid, and proline with (E)-2-oxoindolin-3-ylideneacetyl sultam were theoretically studied through DFT calculations at the M06-2X/6-31G(d,p) level in methanol.

Biological Activity of Two Anticancer Pt Complexes with a Cyclohexylglycine Ligand against a Colon Cancer Cell Line: Theoretical and Experimental Study.

Because of their extraordinary ability to disrupt the natural structure of nucleic acids, metal complexes could be used in cancer therapy. In this study, cyclohexylglycine (HL) as a ligand and two new Pt complexes, [Pt(NH3)2(L)]NO3 (1) and [Pt(bipy)(L)]NO3 (2), were synthesized and characterized by elemental analysis, LC-MS, UV-vis spectrometry, FT-IR, 1H NMR spectroscopy, 13C NMR spectroscopy, 195Pt NMR spectroscopy, HPLC analysis, and single-crystal X-ray diffraction. Complex 2 crystallized in the orthorhombic Pbca space group, and density functional theory (DFT) was used to describe its structural parameters were described in detail. These complexes can be classified as oral medications and drug-like molecules based on a comparison of their absorption, distribution, metabolism, and excretion assessment. Quantum chemical descriptors (QCDs) were determined using DFT calculations to predict the tendency of DNA to approach these complexes. During the determination of the function of the metallodrug in DNA binding, the fluorescence data indicated that static quenching took place for all ligands and complexes with higher DNA binding affinity. CD and isothermal absorption studies indicate the presence of electrostatic and groove binding for the amine derivative and that DNA binds with the bipy moiety via groove binding. Furthermore, the interaction modes were determined using molecular docking to investigate the binding of these compounds with the target DNA molecule. According to docking investigations, binding energies of -5.7, -11.56, and -10.00 kcal/mol for HL and complexes 1 and 2, respectively, indicate partially electrostatic and groove binding. The anticancer activities of the Pt(II) complexes were tested against the HCT116 human colon cancer cell line, with IC50 values of 35.51 and 51.33 µM for 1 and 2, respectively, after 72 h. These values show that the inhibitory effect of complex 1 was better than those of 2 and carboplatin (IC50 = 51.94 µM).

Synthesis of triarylpyridines with sulfonate and sulfonamide moieties via a cooperative vinylogous anomeric-based oxidation.

Herein, novel magnetic nanoparticles with pyridinium bridges namely Fe3O4@SiO2@PCLH-TFA through a multi-step pathway were designed and synthesized. The desired catalyst and its corresponding precursors were characterized with different techniques such as Fourier transform infrared (FT-IR) spectroscopy, 1H NMR, 13C NMR, Mass spectroscopy, energy dispersive X-ray (EDX) analysis, thermogravimetric/derivative thermogravimetry (TG/DTG) analysis, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). In addition, the catalytic application of the prepared catalyst in the synthesis of new series of triarylpyridines bearing sulfonate and sulfonamide moieties via a cooperative vinylogous anomeric-based oxidation was highlighted. The current trend revealed that the mentioned catalyst shows high recoverability in the reported synthesis.

Humidity-Induced Structural Transformation in Pseudopolymorph Coordination Polymers.

Three cadmium coordination polymers, namely, {[CdL(OAc)2](C2H5OH)}n (1), {[CdL(OAc)2](CH3CN)}n (2), and [CdL(OAc)2(H2O)]n (3), were synthesized by an exoditopic 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene Schiff base ligand (L) and cadmium acetate in the presence of different solvent systems. Single-crystal X-ray diffraction, powder X-ray diffraction, and thermogravimetric analysis showed that 1D ladder pseudopolymorphic compounds (1 and 2) transformed to the solvent-free 1D linear compound 3 through a rare case of water absorption from air at room temperature. Interestingly, compound 3 was transformed to compound 1 through a dissolution-recrystallization structural transformation process. The results illustrated that solvents and humidity have an important role in the formation of pseudopolymorphs with the same or different structural motifs.

Chemoselective synthesis of fully substituted pyrroles via a one-pot four-component isocyanide-based reaction.

Small-ring heterocycles comprising pyrrole and pyrazole are well known for their rich biological properties. In this article, an efficient green sonochemical approach was designed for the synthesis of novel, fully substituted pyrroles connected to pyrazole scaffolds via a one-pot, four-component isocyanide-based sequential reaction. This reaction was carried out using various 5-amino-pyrazoles, aldehydes, dialkyl acetylenedicarboxylates and isocyanides for the synthesis of fully functionalized pyrroles with high chemoselectivity in the presence of a catalytic amount of PTSA·H2O, in good to excellent yields under ultrasound irradiation. This waste-free (-H2O) reaction exhibited a high atom economy and step economy via creating four new bonds, including two C-N and two C-C bonds, and the formation of two five-member heterocycles which are connected in a single operation. The mechanism of this four-component domino process involved sequential imination-dipolar cyclization-[1,5]-H shift reactions. The synthesized compounds possess interesting fluorescence features, and the bioactive scaffolds might attract great interest in the fields of clinical diagnostics and biomedical research in the future.

Iodide-Catalyzed Selenium-Assisted Sequential Multicomponent Synthesis of a Luminescence Benzo-Oxazino-Isoindole Framework.

We have described an unexpected pathway using the R-NC/Se system for the synthesis of the unreported benzo-oxazino-isoindole framework by the iodide-catalyzed selenium-assisted sequential multicomponent reaction of the Knoevenagel adduct of ninhydrin and malononitrile, isocyanide, amine, and elemental selenium under mild reaction conditions. The photophysical properties of the products were investigated by absorption and emission spectroscopy, revealing that the new heterocyclic system has good fluorescence properties.

Magnetic chitosan nanocomposite: As a novel catalyst for the synthesis of new derivatives of N-sulfonylamidine and N-sulfonylimidate.

This study reports the synthesis and characterization of a highly active catalyst based on chelated copper iodide on magnetic chitosan-salicylaldehyde Schiff base. This catalyst was successfully used for the three-component reaction of N-propargylphthalimide, tosylazide, and NH or OH containing nucleophiles to access new classes of N-sulfonylamidine or N-sulfonylimidate derivatives. The products, which were constructed via an in situ generated sulfonyl keteneimine intermediate, were obtained in good to excellent yields. Short reaction times, easy separation and reusability without significant loss of catalyst activity were found to be the notable features of this synthetic protocol.

Organocatalytic synthesis of enantiopure spiro acenaphthyl-pyrrolizidine/pyrrolidines: justifying the regioselectivity based on a distortion/interaction model.

An efficient organocatalytic [3 + 2] reaction with Schreiner's thiourea organocatalyst for the synthesis of a small library of novel enantiopure stable spiroacenaphthyl-pyrrolidines/pyrrolizidines with high regio- and diastereoselectivity (up to 99%) is described for the first time. These chiral compounds were synthesized by a three-component 1,3-dipolar cycloaddition of (E)-1-(2-oxoacenaphthylen-1(2H)-ylidene) pyrrolidin-1-ium-2-ide as a dipolar and (S)-cinnamoyl/crotonoyl oxazolidinone as a dipolarophile. The absolute configuration of cycloadducts was confirmed by X-ray diffraction analysis. The origin of catalyst reactivity and regio- and stereoselectivity was investigated through DFT calculations. DFT calculations showed that the regioselectivity was controlled by the distortion (deformation) of reactants and Schreiner's thiourea acts as a LUMO-lowering catalyst.