Performance of 4,5-diphenyl-1H-imidazole derived highly selective 'Turn-Off' fluorescent chemosensor for iron(III) ions detection and biological applications.

Two fluorescent chemosensors, denoted as chemosensor 1 and chemosensor 2, were synthesized and subjected to comprehensive characterization using various techniques. The characterization techniques employed were Fourier-transform infrared (FTIR), proton (1 H)- and carbon-13 (13 C)-nuclear magnetic resonance (NMR) spectroscopy, electrospray ionization (ESI) mass spectrometry, and single crystal X-ray diffraction analysis. Chemosensor 1 is composed of a 1H-imidazole core with specific substituents, including a 4-(2-(4,5-c-2-yl)naphthalene-3-yloxy)butoxy)naphthalene-1-yl moiety. However, chemosensor 2 features a 1H-imidazole core with distinct substituents, such as 4-methyl-2-(4,5-diphenyl-1H-imidazole-2-yl)phenoxy)butoxy)-5-methylphenyl. Chemosensor 1 crystallizes in the monoclinic space group C2/c. Both chemosensors 1 and 2 exhibit a discernible fluorescence quenching response selectively toward iron(III) ion (Fe3+ ) at 435 and 390 nm, respectively, in dimethylformamide (DMF) solutions, distinguishing them from other tested cations. This fluorescence quenching is attributed to the established mechanism of chelation quenched fluorescence (CHQF). The binding constants for the formation of the 1 + Fe3+ and 2 + Fe3+ complexes were determined using the modified Benesi-Hildebrand equation, yielding values of approximately 2.2 × 103 and 1.3 × 104 M-1 , respectively. The calculated average fluorescence lifetimes for 1 and 1 + Fe3+ were 2.51 and 1.17 ns, respectively, while for 2 and 2 + Fe3+ , the lifetimes were 1.13 and 0.63 ns, respectively. Additionally, the applicability of chemosensors 1 and 2 in detecting Fe3+ in live cells was demonstrated, with negligible observed cell toxicity.

Three-Component Reaction of 3-Formyl-6-Methylchromone, Primary Amines, and Secondary Phosphine Oxides: A Synthetic and Mechanistic Study.

A fast, mild, and efficient catalyst-free approach has been developed for the synthesis of chromonyl-substituted α-aminophosphine oxides by the three-component reaction of 3-formyl-6-methylchromone, primary amines, and secondary phosphine oxides at ambient temperature. Carrying out the reaction with aliphatic amines or aminoalcohols at a higher temperature (80 °C), phosphinoyl-functionalized 3-aminomethylene chromanones were formed instead of the corresponding chromonyl-substituted α-aminophosphine oxides. No reaction occurred when 3-formyl-6-methylchromone and secondary phosphine oxides were reacted with aromatic amines in the absence of any catalyst. Applying a basic catalyst, the formation of the phosphinoyl-functionalized 3-aminomethylene chromanones was observed; however, the reaction was not complete. Detailed experimental and quantum chemical studies were performed to study the transformation. Moreover, the in vitro cytotoxicity of phosphinoyl-functionalized 3-aminomethylene chromanones was also investigated in three different cell lines, such as human lung adenocarcinoma (A549), mouse fibroblast (NIH/3T3), and human promyelocytic leukemia (HL60) cells. Several derivatives showed modest activity against the human promyelocytic leukemia (HL60) cell line.

Synthesis, crystal structure and molecular docking study of novel isoxazole derivatives as CYP450 inhibitors in search of anticancer agents.

Synthesis of some novel isoxazole derivatives and their molecular docking with enzymes from CYP450 family carried out using erlotinib, gemcitabine and ketoconazole as reference drugs are reported in this work. Eight isoxazole derivatives of 3,4-substituted phenyl 3-chloroacrylaldehyde and one isoxazole derivative of cinnamaldehyde were synthesized. A molecular docking study of all nine compounds shows good docking score compared to standard drugs erlotinib, gemcitabine and ketoconazole. 4-OH and 4-F derivatives were found to have strong affinity for all six CYP450 proteins under study in the present work. 4-F and 3-NO2 derivatives could be a suitable lead compound inhibitor to CYP1A2 followed by 4-OH derivatives. 4-OH derivative with significant binding affinity showed encouraging inhibition of CYP1A2, CYP2C9, CYP2C8, CYP2C19 and CYP2D6. The current predictions over these nine isoxazole derivatives of 3,4-substituted phenyl 3-chloroacrylaldehyde will be needed to be further investigated in vivo and in vitro conditions to identify the optimum therapeutic efficacy. Synthesis of the isoxazole derivatives is the first known report of the Knoevenagal condensation of acrylaldehyde derivatives to form isoxazole derivatives as per the literature survey. A detailed crystal structure study of five analogues gives insight into the solid-state structural features of this new framework with isoxazole moieties.Communicated by Ramaswamy H. Sarma.

Glasdegib Dimaleate: Synthesis, Characterization and Comparison of Its Properties with Monomaleate Analogue.

Glasdegib is a recently approved drug for the treatment of acute myeloid leukemia. It is formulated and marketed in monomaleate salt form. In our investigation, we were able to prepare a glasdegib dimaleate form, which could, in theory, exist in double-salt form or as a mixture of salt and co-crystal species. Therefore, the obtained crystals of glasdegib dimaleate were characterized via 15N ssNMR and single-crystal X-ray diffraction, which revealed that the obtained glasdegib dimaleate exists in double-salt form. This is a surprising finding based on the pKa values for glasdegib and maleic acid. Furthermore, we fully characterized the new dimaleate form using thermal analyses (DSC and TGA) and spectroscopy (IR and Raman). Finally, the physicochemical properties, such as solubility and chemical stability, of both forms were determined and compared.

High temperature spin crossover behaviour of mononuclear bis-(thiocyanato)iron(II) complexes with judiciously designed bidentate N-donor Schiff bases with varying substituents.

We present herein a family of molecular cis-[FeII(X-PPMA)2(NCS)2]·H2O [4-X-N-(phenyl(pyridin-2-yl)methylene)aniline; X-PPMA; X = -Cl (1), -Br (2), and -CH3 (3)] complexes that exhibit spin crossover behaviour above room temperature. Judiciously designed bidentate N-donor Schiff bases of 2-benzoylpyridine and para-substituted anilines in combination with Fe(NCS)2 were used for the synthesis of complexes 1-3. The relatively strong ligand field of the Schiff bases stabilises the low spin state of iron(II) up to 300 K which is evident from magnetic measurements, room temperature Mössbauer spectra and crystallographic bond/angle distortion parameters. Interestingly, complexes 1-3 crystallize in a tetragonal system with either a P43212 or P41212 chiral space group from achiral building units due to the supramolecular helical arrangements of molecules through intermolecular (pyridine)C-H⋯C(NCS) interactions in the crystalline state. Complexes 1 and 2 exhibit complete, gradual and slightly irreversible spin crossover behaviour in the temperature range of 300-500 K with equilibrium temperatures (T1/2) 375 K (1) and 380 K (2). The spin state evolution of iron(II) in complexes 1 and 2 is monitored between 150 K and 450 K through variable temperature crystallographic studies in the warming mode. The structural data are in good agreement with the 94% (1) and 87% (2) high spin conversion of iron(II) at 450 K. At a high temperature (450 K), some minor irreversible ligand motion is noticed in complexes 1 and 2, in addition to a complete solvent loss that may induce the slight irreversibility of the spin crossover. On the other hand, complex 3 shows a complete and gradual spin crossover in the temperature range of 10-475 K with strong irreversible features. The equilibrium temperatures obtained upon first warming (T1/2↑) and second cooling (T1/2↓) are 375 K and 200 K, respectively. In complex 3, the loss of a water molecule triggers strong deviations in the spin crossover behaviour. Moreover, dehydrated complex 3 exhibits photoswitching LIESST effect with a relaxation temperature T(LIESST) = 60 K.

Macrocyclic "tet a"-Derived Cobalt(III) Complex with a N,N'-Disubstituted Hexadentate Ligand: Crystal Structure, Photonuclease Activity, and as a Photosensitizer.

A cobalt(III) complex, [Co(L)]Cl (complex 1, where L = 1,8-[N,N-bis{(3-formyl-2-hydroxy-5-methyl)benzyl}]-1,4,8,11-tetraaza-5,5,7,12,12,14-hexamethylcyclotetradecane) with distorted octahedral geometry has been synthesized and characterized using various spectroscopic techniques. The structure of the ligand has remarkably rich hydrogen intermolecular interactions such as H···H, H···C/C···H, and H···O/O···H that vary with the presence of the metal ion, and the structure of complex 1 has Cl···H interactions; this result has been proved by Hirshfeld surface and two-dimensional (2D) fingerprint maps analyses. The complex exhibits a quasi-reversible Co(III)/Co(II) redox couple with E 1/2 = -0.76 V. Calf thymus DNA (CT DNA) binding abilities of the ligand and complex 1 were confirmed by spectroscopic and electrochemical analyses. According to absorption studies, the ligand and complex 1 bind to CT DNA via intercalative binding mode, with intrinsic binding strengths of 1.41 × 103 and 8.64 × 103 M-1, respectively. A gel electrophoresis assay shows that complex 1 promotes the pUC19 DNA cleavage under dark and light irradiation conditions. Complex 1 has superior antimicrobial activity than the ligand. The cytotoxicity of complex 1 was tested against MDA-MB-231 breast cancer cells with values of IC50 of 1.369 µg mL-1 in the dark and 0.9034 µg mL-1 after light irradiation. Besides, cell morphological studies confirmed the morphological changes with AO/EB dual staining, reactive oxygen species (ROS) staining, mitochondria staining, and Hoechst staining on MDA-MB-231 cancer cells by fluorescence microscopy. Complex 1 was found to be a potent antiproliferative agent against MDA-MB-231 cells, and it can induce mitochondrial-mediated and caspase-dependent apoptosis with activation of downregulated caspases. The biotoxicity assay of complex 1 on the development of Artemia nauplii was evaluated at an IC50 value of 200 µg mL-1 and with excellent biocompatibility.

PMDTA-catalyzed multicomponent synthesis and biological activity of 2-amino-4H-chromenes containing a phosphonate or phosphine oxide moiety.

A new approach for the preparation of (2-amino-3-cyano-4H-chromen-4-yl)phosphonate derivatives is described. The multicomponent reaction of salicylaldehydes, malononitrile and dialkyl phosphites catalyzed by pentamethyldiethylenetriamine (PMDTA) provided the bicyclic derivatives in high yields. The method developed did not require chromatographic separation, since the products could be recovered from the reaction mixture by simple filtration. Our approach made also possible condensation with secondary phosphine oxides, and this reaction has not been previously reported in the literature. The crystal structures of five derivatives were studied by single-crystal XRD analysis. The in vitro cytotoxicity on different cell lines and the antibacterial activity of the (2-amino-4H-chromen-4-yl)phosphonates synthesized were also explored. According to the IC50 values determined, several derivatives showed moderate or promising activity against mouse fibroblast (NIH/3T3) and human promyelocytic leukemia (HL-60) cells. Furthermore, three (2-amino-3-cyano-4H-chromen-4-yl)phosphine oxides were active against selected Gram-positive bacteria.

Self-Assembly of Multinuclear Sandwich Silver(I) Complexes by Cooperation of Hexakis(azaheteroaryl)benzene Ligands, Argentophilic Interactions, and Fluoride Inclusion.

Self-assembly of AgOTf and AgF with the hexatopic ligands hexakis(pyridin-2-yl)benzene (2) and 2,4,6-tris(pyridin-2-yl)-1,3,5-tris(quinolin-2-yl)benzene (3) affords the discrete sandwich-shaped complexes [Ag4F(2)2](OTf)3, [Ag4F(3)2](OTf)3, and [Ag5F(2)2](OTf)4. The solid-state structures of the complexes were characterized by single-crystal X-ray diffraction analysis, which revealed that the fluoride anion is coordinated in the center of the Ag4-square or Ag5-pentagon units which are positioned between two molecules of the hexakis(azaheteroaryl)benzene. The generation of complexes is dictated by a unique cooperation of ligand coordination, argentophilicity, and fluoride anion inclusion. All three complexes adopt highly symmetrical structures in solution, as evidenced by appearance of one set of proton resonances for the two ligands arranged face to face.

Macrocyclic "tet a" derived colorimetric sensor for the detection of mercury cations and hydrogen sulphate anions and its bio-imaging in living cells.

A mono-N-substituted probe L containing a bromosalicylaldehyde pendant arm attached to a tetraazamacrocyclic "tet a" moiety was synthesized via straight forward reaction. The probe L crystallizes in a monoclinic P21/n space group. The probe L displayed quick sensitivity and selectivity towards Hg2+ ions due to its hopeful Chelation Enhancement Quenching (CHEQ) feature. Interestingly, the probe L exhibits turn-off fluorescence response to Hg2+ ion and turn-on fluorescence signals to HSO4- ions. When the probe L was complexed with HSO4- in 1:1 mode (L + HSO4- formation), improved turn-on fluorescence emission was detected due to the chelation enhanced fluorescence effect through sensor complex. The macrocyclic "tet a" probe L exhibited a binding constant value of 3.89 × 106 M-1 and 5.58 × 105 M-1 for Hg2+ and HSO4-, respectively. Probe L exhibited good selectivity to Hg2+ rather than other common metal ions and HSO4- over other common anions. The limit of detection (LOD) of Hg2+ and HSO4- were found to be 1 nM and 7 µM, respectively. The time-resolved fluorescence emission single-photon counting study was used to determine the average lifetime value for the probe L and L + HSO4- ions as 0.47 and 1.02 ns, respectively. The practical application of the probe in visualizing intracellular Hg2+ and HSO4- ions distribution in live Artemia salina was demonstrated. Furthermore, the probe L with Hg2+cations was found to be cytotoxic against breast cancer cells in nature and can be delivered as an anticancer agent. Besides the probe L with HSO4- exhibit strong fluorescence emission with low cytotoxicity, and it can be recommended for live-cell imaging.

Role of Ligands in the Uptake and Reduction of V(V) Complexes in Red Blood Cells.

The interaction with erythrocytes of four [VVO2L2]- complexes, with L = picolinate (pic), 5-cyanopicolinate (picCN), 3-aminopyrazine-2-carboxylate (przNH2), and 1,2-dimethyl-3-hydroxy-4(1 H)-pyridinonate (dhp), was studied. The thermodynamic stability at physiological pH is: [VVO2(dhp)2]- > [VVO2(przNH2)2]- > [VVO2(pic)2]- > [VVO2(picCN)2]-. With picCN and pic, V exists at physiological pH as H2VVO4-, with przNH2 as a mixture of H2VVO4- and [VVO2(przNH2)2]- and with dhp as [VVO2(dhp)2]-. In the systems with pic and picCN, H2VVO4- and the ligands cross the erythrocyte membrane independently, with dhp the uptake occurs by diffusion, whereas with przNH2 both the mechanisms are active. Inside erythrocytes stable VIVOL2 complexes are formed, indicating that there is no relationship with the stability and redox state of the administered compounds and that, if the metal ion changes its oxidation state in the cytosol as V does, unstable complexes in the extracellular medium could become stable inside the cells and contribute to the pharmacological action.

Supramolecular architectures in Co(II) and Cu(II) complexes with thiophene-2-carboxylate and 2-amino-4,6-dimethoxypyrimidine ligands.

The coordination chemistry of mixed-ligand complexes continues to be an active area of research since these compounds have a wide range of applications. Many coordination polymers and metal-organic framworks are emerging as novel functional materials. Aminopyrimidine and its derivatives are flexible ligands with versatile binding and coordination modes which have been proven to be useful in the construction of organic-inorganic hybrid materials and coordination polymers. Thiophenecarboxylic acid, its derivatives and their complexes exhibit pharmacological properties. Cobalt(II) and copper(II) complexes of thiophenecarboxylate have many biological applications, for example, as antifungal and antitumor agents. Two new cobalt(II) and copper(II) complexes incorporating thiophene-2-carboxylate (2-TPC) and 2-amino-4,6-dimethoxypyrimidine (OMP) ligands have been synthesized and characterized by X-ray diffraction studies, namely (2-amino-4,6-dimethoxypyrimidine-κN)aquachlorido(thiophene-2-carboxylato-κO)cobalt(II) monohydrate, [Co(C5H3O2S)Cl(C6H9N3O2)(H2O)]·H2O, (I), and catena-poly[copper(II)-tetrakis(µ-thiophene-2-carboxylato-κ(2)O:O')-copper(II)-(µ-2-amino-4,6-dimethoxypyrimidine-κ(2)N(1):N(3))], [Cu2(C5H3O2S)4(C6H9N3O2)]n, (II). In (I), the Co(II) ion has a distorted tetrahedral coordination environment involving one O atom from a monodentate 2-TPC ligand, one N atom from an OMP ligand, one chloride ligand and one O atom of a water molecule. An additional water molecule is present in the asymmetric unit. The amino group of the coordinated OMP molecule and the coordinated carboxylate O atom of the 2-TPC ligand form an interligand N-H...O hydrogen bond, generating an S(6) ring motif. The pyrimidine molecules also form a base pair [R2(2)(8) motif] via a pair of N-H...N hydrogen bonds. These interactions, together with O-H...O and O-H...Cl hydrogen bonds and π-π stacking interactions, generate a three-dimensional supramolecular architecture. The one-dimensional coordination polymer (II) contains the classical paddle-wheel [Cu2(CH3COO)4(H2O)2] unit, where each carboxylate group of four 2-TPC ligands bridges two square-pyramidally coordinated Cu(II) ions and the apically coordinated OMP ligands bridge the dinuclear copper units. Each dinuclear copper unit has a crystallographic inversion centre, whereas the bridging OMP ligand has crystallographic twofold symmetry. The one-dimensional polymeric chains self-assemble via N-H...O, π-π and C-H...π interactions, generating a three-dimensional supramolecular architecture.

Tris(3-chloro-pentane-2,4-dionato-κ(2)O,O')iron(III).

In the title compound, [Fe(C(5)H(6)ClO(2))(3)], the Fe(III) cation is situated on a twofold rotation axis and is coordinated by six O atoms from three 3-chloro-pentane-2,4-dionate ligands in a slightly distorted octa-hedral environment. Fe-O bond lengths are in the range 1.9818 (18)-1.9957 (18) Å. The trans O-Fe-O angles are 169.06 (13) and 171.54 (8)°, whereas the corresponding cis angles are in the range 84.81 (10)-100.68 (12)°. In the crystal, mol-ecules are linked via C-H⋯Cl inter-actions.

Nickel-quinolones interaction. Part 5-Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones.

The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N'-donor heterocyclic ligand 2,2'-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2'-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2'-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)(2)(2,2'-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)(2)(H(2)O)(2)], [Ni(quinolonato)(2)(2,2'-bipyridine)] and [Ni(quinolonato)(2)(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase.

Nickel-quinolones interaction: part 3--Nickel(II) complexes of the antibacterial drug flumequine.

Nickel(II) complexes with the first-generation quinolone antibacterial agent flumequine in the presence or absence of nitrogen donor heterocyclic ligands (4-benzylpyridine, pyridine, 2,2'-bipyridine or 1,10-phenanthroline) have been structurally characterized by physicochemical and spectroscopic techniques. The experimental data suggest that flumequine acts as deprotonated bidentate ligand coordinated to Ni(II) through the carboxylato and ketone oxygen atoms. The crystal structures of bis(4-benzylpyridine)bis(flumequinato)nickel(II) 2, (2,2'-bipyridine)bis(flumequinato)nickel(II) 4 and (1,10-phenanthroline)bis(flumequinato)nickel(II) 5 have been determined by X-ray crystallography and are the first crystal structures of flumequinato complexes reported. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes bind to CT DNA and bis(aqua)bis(flumequinato)nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in DMSO solution and in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that in the presence of CT DNA they bind to CT DNA by the intercalative binding mode. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.

Nickel-quinolones interaction. Part 2--interaction of nickel(II) with the antibacterial drug oxolinic acid.

The mononuclear nickel(II) complexes with the first-generation quinolone antibacterial agent oxolinic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized. The experimental data suggest that oxolinic acid acts as deprotonated bidentate ligand coordinated to Ni(II) ion through the ketone and carboxylato oxygens. The crystal structure of (2,2'-bipyridine)bis(oxolinato) nickel(II), 2 has been determined by X-ray crystallography. The cyclic voltammograms of the complexes recorded in dmso solution and in 1/2 dmso/buffer (containing 150mM NaCl and 15mM trisodium citrate at pH 7.0) solution have shown that in the presence of calf-thymus DNA (CT DNA) they can bind to CT DNA by the intercalative binding mode. UV study of the interaction of the complexes with CT DNA has shown that the complexes bind to CT DNA and bis(aqua)bis(oxolinato) nickel(II) exhibits the highest binding constant to CT DNA. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.