Pyridyl Substituents Research Articles

The influence of the pyridyl substituent in N-methyl-P,P-diphenyl-N-2-pyridinyl-phosphinous amide ligand on the coordination chemistry of group 6B metal carbonyl derivatives

The reaction of N-methyl-P,P-diphenyl-N-2-pyridinyl-phosphinous amide (1) with group 6B metal hexa, tetra, and tricarbonyls yielded the same octahedral complexes cis-M(CO)4[1-κ2P,Npy] (M = Cr(2), Mo(3), W(4)) in which the ligand chelates only in a bidentate fashion through its phosphorus atom and pyridyl N-atom. Compounds 1–4 were identified and characterized by multinuclear NMR spectroscopy (1H, 13C, 31P NMR), elemental analysis, IR and UV–Vis spectroscopy. Complexes 2–4 exhibited weak metal-to-ligand charge transfer transitions unaffected by solvent polarity. Crystal structure determination is carried out on complex 4.

Ethyl 5-Hydroxy-2-methyl-1-(pyridin-2-ylmethyl)benzo[g]indole-3-carboxylate

Indole ring is widely represented in natural compounds, as well as in a great variety of drugs. In this paper, the synthesis of a 5-hydroxybenzoindole derivative carrying a pyridyl substituent on position 1 is reported. The method involved no chromatography for purification and used solvents and catalysts of very low toxicity.

A Survey of the Angular Distortion Landscape in the Coordination Geometries of High-Spin Iron(II) 2,6-Bis(pyrazolyl)pyridine Complexes.

Reaction of 2,4,6-trifluoropyridine with sodium 3,4-dimethoxybenzenethiolate and 2 equiv of sodium pyrazolate in tetrahydrofuran at room temperature affords 4-(3,4-dimethoxyphenylsulfanyl)-2,6-di(pyrazol-1-yl)pyridine (L), in 30% yield. The iron(II) complexes [FeL2][BF4]2 (1a) and [FeL2][ClO4]2 (1b) are high-spin with a highly distorted six-coordinate geometry. This structural deviation from ideal D2d symmetry is common in high-spin [Fe(bpp)2]2+ (bpp = di{pyrazol-1-yl}pyridine) derivatives, which are important in spin-crossover materials research. The magnitude of the distortion in 1a and 1b is the largest yet discovered for a mononuclear complex. Gas-phase DFT calculations at the ω-B97X-D/6-311G** level of theory identified four minimum or local minimum structural pathways across the distortion landscape, all of which are observed experimentally in different complexes. Small distortions from D2d symmetry are energetically favorable in complexes with electron-donating ligand substituents, including sulfanyl groups, which also have smaller energy penalties associated with the lowest energy distortion pathway. Natural population analysis showed that these differences reflect greater changes to the Fe-N{pyridyl} σ-bonding as the distortion proceeds, in the presence of more electron-rich pyridyl donors. The results imply that [Fe(bpp)2]2+ derivatives with electron-donating pyridyl substituents are more likely to undergo cooperative spin transitions in the solid state. The high-spin salt [Fe(bpp)2][CF3SO3]2, which also has a strong angular distortion, is also briefly described and included in the analysis.

Photoisomerization mechanism of iminoguanidinium receptors from spectroscopic methods and quantum chemical calculations.

The hydrazone functional group, when coupled with a pyridyl substituent, offers a unique class of widely tunable photoswitches, whose E-to-Z photoisomerization equilibria can be controlled through intramolecular hydrogen bonding between the N-H hydrazone donor and the pyridyl acceptor. However, little is known about the photoisomerization mechanism in this class of compounds. To address this issue, we report a pyridine-appended iminoguanidinium photoswitch that is functionally related to acylhydrazones and provides insight into the photoisomerization processes between the E and Z configurations. The E-to-Z photoisomerization of the E-2-pyridyl-iminoguanidinium cation (2PyMIG) in DMSO, prepared as the bromide salt, was quantified by 1H NMR, and probed in real time with ultrafast laser spectroscopy. The photoisomerization process occurs on a picosecond timescale, resulting in low fluorescence yields. The multiconfigurational reaction path found with the growing string method features a small barrier (4.3 or 6.5 kcal mol-1) that the E isomer in the π-π* state must overcome to reach the minimum energy conical intersection (MECI) connecting the E and Z isomers of 2PyMIG. While two possible pathways exist depending on the orientation of the pyridine ring, both exhibit the same qualitative features along the path and at their MECIs, involving simultaneous changes in the CCNN and CNNC dihedral angles. Furthermore, the ground state barrier for pyridine ring rotation is readily accessible, thus a low barrier pathway to the experimentally observed Z isomer exists for both MECIs leading to a transition from the E isomer to photoproduct. Combining multiconfigurational reaction path calculations using growing string method with time-resolved fluorescence spectroscopy provided crucial insights into the photoisomerization process of 2PyMIG, resulting in both the computational and experimental results pointing to rapid photoisomerization via a surface crossing between the singlet π-π* and the ground states.

Dual-targeting compounds possessing enhanced anticancer activity via microtubule disruption and histone deacetylase inhibition

Dual-targeting anticancer agents 4–29 are designed by combining the structural features of purine-type microtubule-disrupting compounds and HDAC inhibitors. A library of the conjugate compounds connected by appropriate linkers was synthesized and found to possess HDACs inhibitory activity and render microtubule fragmentation by activating katanin, a microtubule-severing protein. Among various zinc-binding groups, hydroxamic acid shows the highest inhibitory activity of Class I HDACs, which was also reconfirmed by three-dimensional quantitative structure-activity relationship (3D-QSAR) pharmacophore prediction. The purine–hydroxamate conjugates exhibit enhanced cytotoxicity against MDA-MB231 breast cancer cells, H1975 lung cancer cells, and various clinical isolated non-small-cell lung cancer cells with different epidermal growth factor receptor (EGFR) status. Pyridyl substituents could be used to replace the C2 and N9 phenyl moieties in the purine-type scaffold, which can help to improve the solubility under physiological conditions, thus increasing cytotoxicity. In mice treated with the purine–hydroxamate conjugates, the tumor growth rate was significantly reduced without causing toxic effects. Our study demonstrates the potential of the dual-targeting purine–hydroxamate compounds for cancer monotherapy.

Interfacial self-assembly of Cd2+-tetraphenylethylene coordination polymers and their photophysical properties in Langmuir-Blodgett films

Molecular arrangement and orientation of tetraphenylethylene (TPE) unit in the highly ordered thin films and aggregates can effectively limit its conformation that results in strong effect on the excited energy transfer process and luminescent behaviors under irradiation. We report here an interfacial self-assembly of metal-TPE coordination polymer (CP) ultrathin films and their aggregate-induced emission (AIE) behaviors. After connected with pyridyl or benzimidazole substituents, the tetradentate TPEs as synthesized are used as the multidentate linkers to coordinate with the Cd2+ ions to produce aggregates in the solutions, and to form well-defined two- and three-dimensional organized Cd-TPE CP multilayers at the air-water interfaces by the Langmuir-Blodgett (LB) method. It is revealed that, in addition to the aggregation-induced emission, the following external factors have also large effects on the luminescence of TPEs, including the coordination bonding in the CPs, in plane and interlayer molecular interaction in the LB films; both of them can restrict the intramolecular motion or rotation of TPE unit. Because of these external effects, the emission lifetime of TPEs reaches to approximately 5–10 times longer in some Cd-TPE CP LB films than that in the solutions. Further, the luminescent emission wavelengths and colors of LB films can be tuned to some extent by the in-plane and interlayer molecular interaction. Finally, it is demonstrated that the luminescent emissions and colors of the Cd-TPPE CP LB films is selectively sensing to methanol and formic acid in the gas phase with good reversibility and reproductivity.

Metal carbonyl mediated rearrangement of 5-(2-oxoalkyl)-1,2,4-oxadiazoles: synthesis of fully substituted pyrimidines.

Variously substituted ethyl 6-oxo-1,6-dihydropyrimidine-5-carboxylates can be easily prepared by a metal carbonyl mediated rearrangement of ethyl 3-oxo-2-(1,2,4-oxadiazol-5-yl)propanoates. The irradiation of a mixture of oxadiazoles and Fe(CO)5 in wet solvents with a 365 nm LED at room temperature for 2 h followed by heating at 80 °C for 2 h gives pyrimidines in up to 90% yield. This procedure enables the preparation of 6-oxo-1,6-dihydropyrimidine-5-carboxylates with various aryl substituents at the C2 and alkyl or aryl substituents at the C4 position. 1-(1,2,4-Oxadiazol-5-yl)propan-2-ones analogously give 6-methylpyrimidin-4(3H)-ones, albeit in lower yields. Ethyl 6-oxo-1,6-dihydropyrimidine-5-carboxylates can be easily modified at the C6 position by bromination followed by cross-coupling reactions to give pyrimidine-5-carboxylates with pyridyl, amino and ethynyl substituents.

Solid state electrochemical behaviour of porphine in aqueous media

The electrochemical behaviour of porphine was studied by cyclic, differential pulse and square-wave voltammetry, in aqueous media, in the pH range between 3.4 and 9.2. The studies were carried out by solid state voltammetry with the insoluble porphine mechanically transferred onto the glassy carbon electrode. The porphine redox mechanism was established by comparison with the redox behaviour of pyrrole, 1,4-dimethylpyridinium p-toluenesulfonate, and two meso-substituted porphyrins, 5,10,15,20-tetraphenyl-21H,23H-porphine (TPP) and 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (TPyP). The porphine oxidation is a two-step, irreversible and pH-dependent process, each oxidation step involving the loss of one electron from the lone pairs in the nitrogen atoms. The porphine reduction is a one-step, irreversible and pH-dependent process, involving the acceptance of one electron and one proton. A second reduction step at more negative potentials is probable, but cannot be detected due to the limitation of the GCE potential range. The presence of phenyl and pyridyl substituents at meso position disturbs the electron density and the planarity of the porphine ring, which results in a shift of the porphine redox potentials to more positive values, consistent with a more difficult oxidation and a facilitated reduction, as observed for TPP and TPyP.

Diketopyrrolopyrrole Derivatives as Photosensitizing Agents against Staphylococcus aureus.

Diketopyrrolopyrrole (DPP) derivatives containing sulfonamide (Sulfonamide-DPP), pyridyl (Dipyridyl-DPP) and N-methylpyridyl (MePyridyl-DPP) substituents were assessed as antibacterial photosensitizers. Non-charged DPPs showed an intense absorption band centered at about 480 nm and green fluorescence emission (ΦF ~ 0.7) in acetonitrile. The absorption of MePyridyl-DPP was bathochromically shifted at 510 nm, with decreased fluorescence emission. Sulfonamide-DPP and Dipyridyl-DPP photosensitized the formation of O2 (1 Δg ) (ΦΔ ~ 0.15-0.17), while the production induced by MePyridyl-DPP was at least 10 times lower. Furthermore, these DPPs produced a photoreduction of NBT similar to that of the control. Photodynamic inactivation induced by DPPs was first investigated at the single-bacterium level of Staphylococcus aureus attached to a surface. After 30 min irradiation, MePyridyl-DPP produced a complete eradication of the bacteria. In bacterial cell suspensions, dicationic DPP induced more than 7 log10 decrease in S. aureus cell survival after 30 min irradiation. Potentiation with iodide anions allowed a complete elimination of bacteria after 15 min therapy. This compound was also effective to eliminate S. aureus cells on biofilms. The results show that MePyridyl-DPP bearing two positive groups provides an amphiphilic character to the structure that improves the interaction with the cell envelop. This effect enhances the photocytotoxic activity of MePyridyl-DPP against bacteria.

Synthesis of Chiral 1,4,2-Oxazaphosphorinanes Bearing Pyridyl Substituents

Synthesis of Chiral 1,4,2-Oxazaphosphorinanes Bearing Pyridyl Substituents

Assembly of Sn(IV)-Porphyrin Cation Exhibiting Supramolecular Interactions of Anion···Anion and Anion···π Systems

Trans-diaqua[meso-tetrakis(4-pyridyl)porphyrinato]Sn(IV) dinitrate complexes were assembled in a two-dimensional manner via hydrogen bonding between aqua ligands and pyridyl substituents. Interestingly, this supramolecular assembly was accompanied by unconventional noncovalent interactions, such as anion···anion and anion···π interactions, which were confirmed by X-ray crystallographic analysis. Two nitrate anions close to 2.070 Å were constrained in a confined space surrounded by four hydrogen-bonded Sn(IV)-porphyrin cations. The nitrate anion was also 3.433 Å away from the adjacent pyrrole ring, and the dihedral angle between the two mean planes was estimated to be 7.39°. The preference of the anion···π interaction was related to the electron-deficient π-system owing to the high-valent Sn(IV) center and cationic nature of the porphyrin complex. These two unconventional noncovalent interactions played an important role in the formation of a one-dimensional array with pairs of Sn(IV)-porphyrin cation and nitrate anion.

“Urea to Urea” Approach: Access to Unsymmetrical Ureas Bearing Pyridyl Substituents

AbstractA protocol for the synthesis of unsymmetrical ureas substituted by pyridyl/quinolinyl moiety has been developed. This method concluded in metal‐ and base‐free reamination of N,N‐dimethyl‐N‘‐hetaryl ureas with a wide range of aryl and alkyl amines. The isolated yields vary from 40 to 96% depending on the nucleophilicity of the amines. The scope of this method includes more than 50 examples. The reaction is not hindered by either donor or acceptor groups as well as diverse functionalities. The synthesis can be easily scaled to gram quantities. Theoretical calculations supported by experimental data allowed us to propose a plausible mechanism for the process. This reaction takes place through the intermediate formation of hetaryl isocyanate.magnified image

Combination of tetrapyridylporphyrins and arene ruthenium(II) complexes to treat synovial sarcoma by photodynamic therapy

Four tetrapyridylporphyrin and four dipyridylporphyrin arene ruthenium complexes have been synthesized and characterized. In these complexes, the porphyrin core is either metal-free or occupied by zinc, and the arene ligand of the arene ruthenium units are either the standard methyl-isopropyl-benzene ([Formula: see text]cymene) or the less common phenylpropanol (PhPrOH) derivative. The porphyrin derivatives are coordinated to four arene ruthenium units or only two, in accordance with the number of pyridyl substituents at the periphery of the porphyrins, 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (TPyP) and 5,15-diphenyl-10,20-di(pyridin-4-yl)porphyrin (DPhDPyP). All eight complexes were evaluated as anticancer agents on synovial sarcoma cells, in the presence and absence of light, suggesting that both the arene ligand and the porphyrin core substituent can play a crucial role in fine-tuning the photodynamic activity of such organometallic photosensitizers.

Thallium(III) p‐tosylate‐mediated oxidative [1,2] rearrangement of 2‐naphthyl and 2‐heteroarylchromanones

AbstractA practical and effective approach towards the synthesis of 3‐heteroaryl‐4H‐chromen‐4‐ones by the oxidative [1,2] rearrangement of the respective 2‐heteroaryl chroman‐4‐ones using thallium(III) p‐tosylate is presented. The oxidative rearrangement of α‐ and β‐naphthyl and thiophene substituents behaves like aryl groups; However, pyridyl substituents gave only dehydrogenated products.

Crystal structures of (E)-2-amino-4-methyl-sulfanyl-6-oxo-1-(1-phenyl-ethyl-idene-amino)-1,6-di-hydro-pyrimidine-5-carbo-nitrile and (E)-2-amino-4-methyl-sulfanyl-6-oxo-1-[1-(pyridin-2-yl)ethyl-idene-amino]-1,6-di-hydro-pyrimidine-5-carbo-nitrile.

The title compounds 3a, C14H13N5OS, and 3b, C13H12N6OS, both show an E configuration about the N=C bond and a planar NH2 group. The mol-ecules, which only differ in the presence of a phenyl (in 3a) or pyridyl (in 3b) substituent, are closely similar except for the different orientations of these groups. The amino hydrogen atoms form classical hydrogen bonds; in 3a the acceptors are the oxygen atom and the cyano nitro-gen atom, leading to ribbons of mol-ecules parallel to the b axis, whereas in 3b the acceptors are the oxygen atom and the pyridyl nitro-gen, leading to a layer structure perpendicular to (01).

First‐Row Transition Metals Complexes with Fused Oxazolidine (FOX) Ligands

AbstractIn this comprehensive study, we report the syntheses and crystal structures of 6 fused oxazolidine (FOX) bicycles and 22 complexes with FOX ligands. The structures are compared to the few FOX complexes found in literature. For our investigations, we developed synthetic strategies to selectively synthesize chiral or achiral FOX bicycles with pyridyl substituents. The coordination chemistry of the chiral and achiral FOX compounds with first‐row transition metals is discussed in an in‐depth analysis of the crystal structures. We found that the binding modes of the ligands are dependent on the configuration of the FOX backbone and on the steric demand of the substituents which were introduced to the pyridyl groups. The configuration of the FOX ligands is retained during the coordination of metal(II) ions such as Mn2+, Fe2+, Co2+, Ni2+, Cu2+. Reactions of these metal ions with chiral FOX ligands lead to the formation of chiral complexes. In contrast, stronger Lewis acidic metal(III) ions, such as Fe3+ or Al3+, induce an isomerization of the chiral FOX ligands to their achiral diastereomers.

Osmium-arene complexes with high potency towards Mycobacterium tuberculosis.

The treatment of tuberculosis (TB) poses a major challenge as frontline therapeutic agents become increasingly ineffective with the emergence and spread of drug-resistant strains of Mycobacterium tuberculosis (Mtb). To combat this global health problem, new antitubercular agents with novel modes of action are needed. We have screened a close family of 17 organometallic half-sandwich Os(II) complexes [(arene)Os(phenyl-azo/imino-pyridine)(Cl/I)]+Y– containing various arenes (p-cymene, biphenyl, or terphenyl), and NMe2, F, Cl, or Br phenyl or pyridyl substituents, for activity towards Mtb in comparison with normal human lung cells (MRC5). In general, complexes with a monodentate iodido ligand were more potent than chlorido complexes, and the five most potent iodido complexes (MIC 1.25–2.5 µM) have an electron-donating Me2N or OH substituent on the phenyl ring. As expected, the counter anion Y (PF6–, Cl–, I–) had little effect on the activity. The pattern of potency of the complexes towards Mtb is similar to that towards human cells, perhaps because in both cases intracellular thiols are likely to be involved in their activation and their redox mechanism of action. The most active complex against Mtb is the p-cymene Os(II) NMe2-phenyl-azopyridine iodido complex (2), a relatively inert complex that also exhibits potent activity towards cancer cells. The uptake of Os from complex 2 by Mtb is rapid and peaks after 6 h, with temperature-dependence studies suggesting a major role for active transport. Significance to Metallomics Antimicrobial resistance is a global health problem. New advances are urgently needed in the discovery of new antibiotics with novel mechanisms of action. Half-sandwich organometallic complexes offer a versatile platform for drug design. We show that with an appropriate choice of the arene, an N,N-chelated ligand, and monodentate ligand, half-sandwich organo–osmium(II) complexes can exhibit potent activity towards Mycobacterium tuberculosis (Mtb), the leading cause of death from a single infectious agent. The patterns of activity of the 17 azo- and imino-pyridine complexes studied here towards Mtb and normal lung cells suggest a common redox mechanism of action involving intracellular thiols.

Ascorbate-dependent and ascorbate-independent Mn porphyrin cytotoxicity: anticancer activity of Mn porphyrin-based SOD mimics through ascorbate-dependent and -independent routes

ABSTRACT Objective The aim of this study was to investigate how modifications at the periphery of the porphyrin ring affect the anticancer activity of Mn porphyrins (MnPs)-based SOD mimics. Methods Six compounds: MnTE-2-PyP with a short ethyl chain on the pyridyl ring; MnTnHexOE-2-PyP and MnTnOct-2-PyP with linear 8-atom alkyl chains, but the former with an oxygen atom within the alkyl chain; MnTE-2-PyPhP and MnTPhE-2-PyP with pyridyl and phenyl substituents, were investigated. Cytotoxicity was studied using pII and MDA-MB-231 cancer cell lines. Viability was assessed by the MTT (3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyltetrazolium bromide) assay and cell proliferation was determined by the sulforhodamine B assay. Results Cellular uptake was increased with the increase of the lipophilicity of the compounds, whereas reduction potential (E ½) of the Mn(III)/Mn(II) redox couple shifted away from the optimal value for efficient redox cycling with ascorbate, necessary for ROS production. Amphiphilic MnPs, however, exerted anticancer activity by a mechanism not involving ROS. Conclusion Two different processes account for MnPs cytotoxicity. MnPs with appropriate E ½ act via a ROS-dependent mechanism. Amphiphilic MnPs with suitable structure damage sensitive cellular constituents, leading to the suppression of proliferation and loss of viability. Design of compounds interacting directly with sensitive cellular targets is highly promising in the development of anticancer drugs with high selectivity and specificity.

Simple lattice model of self-assembling metal-organic layers of pyridyl-substituted porphyrins and copper on Au(111) surface.

A simple lattice model of metal-organic adsorption layers self-assembling on a Au(111) surface and based on pyridyl-substituted porphyrins differing in the number of functional groups and their position has been proposed. The model has been parameterized using DFT methods. The ground state analysis of the considered model demonstrates the variety of surface-confined metal-organic networks (SMONs) containing square, linear, and discrete elements appearing in the adsorption layer depending on the partial pressure of the components. The SMONs comprising more symmetrical molecules with a greater number of pyridyl substituents in the porphyrin core exhibit more diverse phase behavior. Structures of the phase diagrams were verified at nonzero temperatures using Grand Canonical Monte Carlo simulations. It was found that the continuous SMONs have higher thermal stability at relatively low partial pressures of the organic component, while the linear and discrete SMONs are more thermally stable at high pressure. Depending on the partial pressure of the organic component, thermal destruction of continuous SMONs occur either through the formation of defects/islands having structures of the linear SMONs, or through the sublimation of individual structural elements. Melting of linear SMONs reveals the appearance of 2D pores or islands of a purely organic phase. The latter fact is confirmed by the experimentally observed coexistence of these phases.

PH-Sensitive Fluorescence Switching of Pyridylanthracenes: The Effect of the Isomeric Pattern.

9,10-substituted anthracenes are known for their useful optical properties like fluorescence, which makes them frequently used probes in sensing applications. In this article, we investigate the fundamental photophysical properties of three pyridyl-substituted variants. The nitrogen atoms in the pyridinium six-membered rings are located in the ortho-, meta-, and para-positions in relation to the anthracene core. Absorption, fluorescence, and transient absorption measurements were carried out and were complemented by theoretical calculations. We monitored the photophysics of the anthracene derivatives in chloroform and water investigating the protonated as well as their nonprotonated forms. We found that the optical properties of the nonprotonated forms are strongly determined by the anthracene chromophore, with only small differences to other 9,10-substituted anthracenes, for example diphenyl anthracene. In contrast, protonation leads to a strong decrease in fluorescence intensity and lifetime. Transient absorption measurements and theoretical calculations revealed the formation of a charge-transfer state in the protonated chromophores, where electron density is shifted from the anthracene moiety toward the protonated pyridyl substituents. While the para- and ortho-derivatives' charge transfer is still moderately fluorescent, the meta-derivative is affected much stronger and shows nearly no fluorescence. This nitrogen-atom-position-dependent sensitivity to hydronium activity makes a combination of these fluorophores very attractive for pH-sensing applications covering a broadened pH range.