Aminomethyl Pyridine Research Articles

A Very Rare Example of a Structurally Characterized 3'-GMP Metal Complex. NMR and Synthetic Assessment of Adducts Formed by Guanine Derivatives with [Pt(Ltri)Cl]Cl Complexes with an N,N',N″ Tridentate Ligand (Ltri) Terminated by Imidazole Rings.

[Pt(N(R)-1,1'-Me2dma)Cl]Cl complexes with tridentate ligands (bis(1-methyl-2-methylimidazolyl)amine, R = H; N-(methyl)bis(1-methyl-2-methylimidazolyl)amine, R = Me) were prepared in order to investigate Pt(N(R)-1,1'-Me2dma)G adducts (G = monodentate N9-substituted guanine or hypoxanthine derivative). Solution NMR spectroscopy is the primary tool for studying metal complexes of nucleosides and nucleotides because such adducts rarely crystallize. However, [Pt(N(H)-1,1'-Me2dma)(3'-GMPH)]NO3·5H2O (5) was crystallized, allowing, to our knowledge, the first crystallographic molecular structure determination for a 3'-GMP platinum complex. The structure is one of only a very few structures of a 3'-GMP complex with any metal. Complex 5 has the syn rotamer conformation, with 3'-GMP bound by N7. All Pt(N(R)-1,1'-Me2dma)G adducts exhibit two new downfield-shifted G H8 signals, consistent with G bound to platinum by N7 and a syn/anti rotamer mixture. Anticancer-active monofunctional platinum(II) complexes have bulky carrier ligands that cause DNA adducts to be distorted. Hence, understanding carrier-ligand steric effects is key in designing new platinum drugs. Ligand bulk can be correlated with the degree of impeded rotation of the G nucleobase about the Pt-N7 bond, as assessed by the observation of rotamers. The signals of syn and anti rotamers are connected by EXSY cross-peaks in 2D ROESY spectra of Pt(N(H)-1,1'-Me2dma)G adducts but not in spectra of Pt(N(H)dpa)G adducts (N(H)dpa = bis(2-picolyl)amine), indicating that rotamer interchange is more facile and carrier-ligand bulk is lower in Pt(N(H)-1,1'-Me2dma)G than in Pt(N(H)dpa)G adducts. The lower steric hindrance is a direct consequence of the greater distance of the G nucleobase from the H4/4' protons in the N(R)-1,1'-Me2dma carrier ligand in comparison to that from the H6/6' protons in the N(H)dpa carrier ligand. Although in 5 the nucleotide is 3'-GMP (not the usual 5'-GMP) and the N(H)-1,1'-Me2dma carrier ligand is very different from those typically present in structurally characterized Pt(II) G complexes, the rocking and canting angles in 5 adhere to long-recognized trends.

Palladium(II) complexes bearing di-(2-picolyl)amine functionalized chrysin fragments. An experimental and theoretical study

A new series of chrysin derivatives containing the di-(2-picolyl)amine (2a–d) moiety have been designed, synthesized, and treated with PdCl2·2CH3CN allowing the preparation of new cationic Palladium(II) complexes (3a–d). Solution-phase studies by 1H NMR spectroscopy of 3a–d revealed that the protons of the methylene groups of the di(2-picolyl)amine fragment are diasterotopic. GIAO/DFT studies were performed to predict the molecular structures of 3a–d by comparing the experimental and theoretical 1H-NMR chemical shifts. The molecular structure of 3c was determined by X-ray crystallographic analysis revealing that di-(2-picolyl)amine fragment is coordinated to the palladium center in a κ3-N,N,N-tridentate fashion in an overall square-planar geometry completed with a chloride atom.

Hybrid metal complexes with opposed biological modes of action – promising selective drug candidates

Abstract The oxidative stress is considered to be involved in the pathogenesis of many diseases. The antioxidative defense system in the living organism regulates the toxic impact of ROS and there is strong evidence that the antioxidants prevent some pathologies including cancer. The specific chemical properties of metal-based drugs impart innovative pharmacological profiles to this type of therapeutic agents, most likely in relation to novel biomolecular mechanisms. This review will focus on a novel approach to design polyfunctional metal-based physiollogically active compounds with opposed modes of action – prooxidant metal center and antioxidant 2,6-dialkylphenol group. The synthesis and anti/prooxidant activity and cytotoxicity studies of novel organometallic/coordination compounds (ferrocenes, complexes with di-(2-picolyl)amine ligand, porphyrins, pyridines, thiols, carboxylates) based on either biogenic metals (Fe, Mn, Co, Cu, Zn, Ni) or exogenic metals (Sn, Au, Rh) are presented and discussed. The results allow us to conclude that combining in one molecule a redox active metal center and cytoprotective functional organic moiety with antioxidative function is a promising way to rational metallodrug design in modern medicinal chemistry.

Redox-active metal complexes with 2,2′-dipicolylamine containing ferrocenyl moiety: Synthesis, electrochemical behavior and biological activity

The novel metal complexes of general formula MCl2·L (M = Cu, Fe, Co, Mn, Zn) based on the di-(2-picolyl)amine ligand L with the redox-active ferrocenyl fragment were synthesized and characterized by elemental analysis, IR, 1H, 13C NMR, UV–vis spectroscopy and MALDI-TOF mass spectrometry. The molecular structure of [ZnCl2L] was established by X-ray crystallography. The redox properties of complexes were studied using cyclic voltammetry (CV) method and feasible schemes of electrochemical transformations were proposed. The antioxidant activity of compounds was tested by various methods. The lipoxygenase (LOX) inhibition activity of the studied compounds was evaluated. The in vitro biological experiments were performed using rat brain homogenates. The results demonstrate that ditopic compounds containing ferrocene and redox active dipicolylamine fragments act as polyfunctional antioxidants. These results let us to conclude that combining in one molecule several redox-active metal centers is a promising way of metallodrug design in modern medicinal chemistry.

Cobalt, nickel, and iron complexes of 8-hydroxyquinoline-di(2-picolyl)amine for light-driven hydrogen evolution.

Novel cobalt, nickel, and iron complexes based on the pentadentate 8-hydroxyquinoline-di(2-picolyl)amine ligand were synthesized and thoroughly characterized. X-ray structures of both the cobalt and iron complexes were also obtained, showing the tendency to adopt a pseudo-octahedral geometry by coordination of an additional sixth ligand. These metal complexes were then studied as potential hydrogen-evolving catalysts (HECs) under both electrochemical and light-driven conditions. In particular, two different photochemical systems were tested involving either Ru(bpy)32+/ascorbic acid or Ir(ppy)2(bpy)+/TEA sensitizer/sacrificial donor couples. The electrochemical results showed that these metal complexes may behave as competent HECs. However, under photochemical conditions, only the cobalt compound displayed substantial hydrogen-evolving activity in both ruthenium- and iridium-based systems. The nickel and iron complexes, on the other hand, exhibited appreciable photocatalytic activity only in the iridium-based photochemical system, while showing negligible hydrogen evolution ability when employed in the ruthenium-based one.

Synthesis of 3-(aminomethyl)pyridine by traceless C3-selective umpolung of 1-amidopyridin-1-ium salts

A natural product inspired rapid access of 3-(aminomethyl)pyridine by one-pot reaction of 1-amidopyridin-1-ium salt with aminal followed by reductive cleavage of the N-N bond is developed. This C3-selective formal C-H activation of pyridine features a traceless umpolung of the 1-amidopyridin-1-ium salt toward a Mannich type C-C bond formation of the in situ generated 1-amido-2-dialkylamino-1,2-dihydropyridine intermediate.

Electrochemical Behavior of Electroactive PVS/PANI Films Containing Chemically Modified Cellulose

Electroactive films containing cellulose modified with cationic and anionic groups were prepared with polyaniline (PANI) and poly (vinyl sulfonic acid) (PVS). The modifications were performed with (aminomethyl) pyridine (AMP), ethylenediamine (EDA), buthylenediamine (BN), bis-(aminopropyl) piperazine (APP), maleic anhydride (MA), and phosphate PO43- groups. The films were prepared using the layer-by-layer (LbL) technique, utilizing dispersed cellulose in a PANI solution forming the PVS/PANI system (cationic or anionic cellulose). Films of unmodified microcrystalline cellulose (MC) were also prepared for comparison. The films were characterized by cyclic voltammetry. The electrochemical responses of PANI present in the film, especially in terms of current density and redox potential, were found to be influenced by the modification of the cellulose.

New copper(II) complexes including pyridine-2,5-dicarboxylic acid: synthesis, spectroscopic, thermal properties, crystal structure and how these complexes interact with purified PON 1 enzyme

We report the synthesis of two square-pyramidal copper(II) complexes, [Cu(2,5-pydc)(2-aepy)(H2O)]·H2O, 1, and [Cu(2,5-pydc)(2-ampy)(H2O)]·H2O, 2 (2-aepy = 2-(aminoethyl)pyridine, 2-ampy = 2-(aminomethyl)pyridine, 2,5-pydc = pyridine-2,5-dicarboxylic acid or isocinchomeronic acid). The synthesized complexes have been characterized by X-ray diffraction, FT-IR, elemental, and thermal analysis techniques. The crystal structure of 1 was established by X-ray analysis. Powder X-ray diffraction analysis showed that the complexes are pure. The inhibition of human serum paraoxonase 1 (PON 1, EC 3.1.8.1) enzyme with these complexes were investigated. We used diethyl 4-nitrophenyl phosphate as a substrate to measure the paraoxonase activity of PON 1 enzyme spectrophotometrically. Complexes 1 and 2 decreased the in vitro PON 1 activity with different inhibition mechanisms. Complexes 1 and 2 inhibited paraoxonase activity of this enzyme as competitively and noncompetitively, respectively.

Synthesis of oxetane/azetidine containing spirocycles via the 1,3-dipolar cycloaddition reaction

Silver catalyzed 1,3-dipolar cycloaddition reactions between methyl 2-(oxetane/azetidine-3 ylidene)acetate as dipolarophiles and imines derived from α-amino acid methyl esters, 2-aminomethyl pyridine, and 2-aminomethyl pyrazine afforded oxetane/azetidine containing spirocycles in 40–77% yield. The use of 3-oxetanone used as the carbonyl compound thermal 1,3-dipolar cycloaddition reactions with secondary α-amino acids or methyl esters resulted in oxetane spirocycles in 62–90% yield.

Radiation synthesis of spherical cellulose-based adsorbent for efficient adsorption and detoxification of Cr(VI)

Spherical cellulose-based adsorbent (2-AMPR) with 2-aminomethyl pyridine was synthesized by radiation method. The adsorption behaviors of 2-AMPR for Cr(VI) removal were evaluated through batch and column experiments. The results presented that the adsorption kinetics well obeyed pseudo-second-order mode and the adsorption isotherm of Cr(VI) followed the Langmuir model with adsorption capacity of 209.6mg/g at optimal pH 2.0. Dynamical experiments revealed that the 2-AMPR could selectively and simultaneously separate and detoxify trace amount of Cr(VI) even from simulated electroplating wastewater including high concentration of Cu(II), Ni(II) and Zn(II) ions. Additionally, FTIR and XPS analysis verified that part of Cr(VI) was reduced to Cr(III) during adsorption process by adsorption–reduction mechanism.

In vitro evaluation of metal chelators as potential metallo- β -lactamase inhibitors.

This study aimed at investigating the use of metal chelators as potential metallo-β-lactamase inhibitors (MBL). The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane-1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2-picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0·06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0·5 and 0·06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0·125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0·06 mg l(-1) against an NDM-1 producing isolate. The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem. In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors.

Label-Free Pyrophosphate Recognition with Functionalized Asymmetric Nanopores.

The label-free detection of pyrophosphate (PPi) anions with a nanofluidic sensing device based on asymmetric nanopores is demonstrated. The pore surface is functionalized with zinc complexes based on two di(2-picolyl)amine [bis(DPA)] moieties using carbodiimide coupling chemistry. The complexation of zinc (Zn(2+) ) ion is achieved by exposing the modified pore to a solution of zinc chloride to form bis(Zn(2+) -DPA) complexes. The chemical functionalization is demonstrated by recording the changes in the observed current-voltage (I-V) curves before and after pore modification. The bis(Zn(2+) -DPA) complexes on the pore walls serve as recognition sites for pyrophosphate anion. The experimental results show that the proposed nanofluidic sensor has the ability to sense picomolar concentrations of PPi anion in the surrounding environment. On the contrary, it does not respond to other phosphate anions, including monohydrogen phosphate, dihydrogen phosphate, adenosine monophosphate, adenosine diphosphate, and adenosine triphosphate. The experimental results are described theoretically by using a model based on the Poisson-Nernst-Planck equations.

Tuning the DNA binding and cleavage of bpa Cu(II) complexes by ether tethers with hydroxyl and methoxy groups

Five bpa (bis(2-picolyl)amine) derivatives (1b, 2e, 3f, 4c, 5d) carrying ether tethers with hydroxyl and methoxy groups, have been synthesized from pyridine aldehyde and the respective amines by reductive amination. Their Cu(II) complexes carrying additional nitrato (6a–b) and perchlorato (7a–e) ligands, respectively, have been characterized and subjected to DNA cleavage studies. Since the hydrolytic DNA cleavage activity of 6a is known from the literature, further experiments comprising the novel derivatives have been carried out. These reveal that derivative 7e was able to generate 10 times more linear DNA in a standard cleavage experiment than 6a. Considering the redox activity of the Cu(II) center, a possible oxidative cleavage activity of this kind of bpa complexes was also investigated.

Novel Cobalt(II) complexes containing N,N-di(2-picolyl)amine based ligands; Synthesis, characterization and application towards methyl methacrylate polymerisation

The reaction of [CoCl2·6H2O] with N′-substituted N,N-di(2-picolyl)amine ligands such as 1-cyclohexyl-N,N-bis(pyridin-2-ylmethyl)methanamine (LA), 2-methoxy-N,N-bis(pyridin-2-ylmethyl)ethan-1-amine (LB), and 3-methoxy-N,N-bis(pyridin-2-ylmethyl)propan-1-amine (LC), yielded [LnCoCl2] (Ln = LA, LB and LC), respectively. The Co(II) centre in [LnCoCl2] (Ln = LA, and LC) adopted distorted bipyramidal geometries through coordination of nitrogen atoms of di(2-picolyl)amine moiety to the Co(II) centre along with two chloro ligands. The 6-coordinated [LBCoCl2] showed a distorted octahedral geometry, achieved through coordination of the two pyridyl units, two chloro units, and bidentate coordination of nitrogen and oxygen in the N′-methoxyethylamine to the Co(II) centre. [LCCoCl2] (6.70 × 104 gPMMA/molCo h) exhibited higher catalytic activity for the polymerisation of methyl methacrylate (MMA) in the presence of modified methylaluminoxane (MMAO) compared to rest of Co(II) complexes. The catalytic activity was considered as a function of steric properties of ligand architecture and increased steric bulk around the metal centre resulted in the decrease catalytic activity. All Co(II) initiators yielded syndiotactic poly(methylmethacrylate) (PMMA).

Synthesis and characterization of ML and ML2 metal complexes with amino acid substituted bis(2-picolyl)amine ligands.

Metal complexes with ML or ML2 stoichiometry have been isolated in the reaction of Zn(NO3)2, ZnBr2 or M(NO3)2/NaBF4, M = Zn(ii), Co(ii) or Ni(ii), with either amino acid or amine substituted tridentate nitrogen ligands based on bis(2-picolyl)amine (bpa) or bis(2-quinaldyl)amine (bqa). The stoichiometry (M : L = 1 : 1 or 1 : 2) and stereochemistry (mer, trans-fac or cis-fac) of the products have been studied by NMR and IR spectroscopy, X-ray single crystal analysis and quantum-chemical calculations with an implicit SMD solvation model.

Intramolecular conversion of N,N-bis(2-picolyl)ureas to cyclic carbamates

Herein, we present a new methodology for preparing 6-membered ring carbamates from a CuI-promoted cyclization of N,N-bis(2-picolyl)amine substituted ureas. The reactions work best in the presence of up to five-fold excess of CuCl at room temperature in a non-nucleophilic solvent such as acetonitrile. Nine examples of the syntheses are presented to yield products in good to excellent amounts.

3.3.1. Synthesis, Spectroscopy and Structural Analysis of Technetium and Rhenium Nitrosyl Complexes

Here we report an overview of our synthetic, spectroscopic and structural studies of technetium and rhenium nitrosyl complexes. We review the results from various notes and short papers reported over the past 15 years and discuss their significance in terms of radiopharmaceutical design. A single new complex is reported, the Re I -NO complex [Re I Cl 2 (NO)(py-N(Et)-py)], in which the tridentate ligand di-(2-picolyl)(N-ethyl)amine, (py-N(Et)-py), is coordinated in a meridional manner. This complex was synthesized from the reaction of the Re I -nitrosyl complex ReCl 2 (NO)(NCMe) 3 ] and the neutral tri-amine ligand py-N(Et)-py in methylene chloride under argon. The bright red species was isolated chromatographically and recrystallized from CH 2 Cl 2 /MeOH under diethylether. A review of literature values for nitrosyl complexes with various ligands bound to the coordination site trans- to the nitrosyl group shows only minor variations in the M-N-O bond angle.

New supported-catalytic systems for atom transfer radical polymerization

The atom transfer radical polymerization (ATRP) was studied using new well-defined functional copolymers (poly(styrene-co-vinylbenzyl chloride) - Poly(S-co-VBC)- modified by di(2-picolyl)amine) as macroligands. Poly(S-co-VBC) copolymers with various proportions of VBC monomer were prepared either by free radical polymerization or by nitroxide-mediated polymerization using a commercially available alkoxyamine (BlocBuilder®). Macroligands were further obtained by post-modification of poly(S-co-VBC) by di(2-picolyl)amine (DIPA) and were then successfully used for the homogeneous ATRP of methyl methacrylate and styrene. We also investigated the ATRP in heterogeneous conditions with the macroligand being supported onto silica Stöber nanoparticles.

Novel imprinted nanocapsule with highly enhanced hydrolytic activity for organophosphorus pesticide degradation and elimination

The removal of organophosphorus pesticide residues is of great importance to environment treatment nowadays. In this work, we designed a novel imprinted hollow nanocapsule which could effectively eliminate organophosphorus pesticide residues remained in water environment. The shell of the methyl parathion imprinted nanocapsule was prepared based on a multi-pyridine-ligand functional monomer, N-(4-vinylbenzyl)-di(2-picolyl)amine. The obtained nanocapsule showed a high catalytic efficiency towards methyl parathion, with an initial hydrolysis rate of 3.1×10−2mM/h, 355-fold relative to the self-hydrolysis of methyl parathion. And a low Km value, 0.6mM, was observed, indicating a good affinity of functional ligand on the nanocapsule towards methyl parathion. Additionally, the obtained hollow nanocapsule could further remove p-nitrophenol generated in the catalytic degradation system, another hazardous substance, by enriching part of p-nitrophenol in its central cavity.

The electrochemical approach to antioxidant activity assay of metal complexes with dipicolylamine ligand, containing 2,6-di-tert-butylphenol groups, based on electrochemical DPPH-test

The novel electrochemical approach to antioxidant activity assay based on the reaction with stable radical 2,2′-diphenyl-1-picrylhydrazyl (DPPH) monitored by the rotating disk electrode (RDE) method was developed. This method has advantages in comparison with usual spectrophotometrical assay since it can be applied to colored compounds and in a wide range of concentrations. The electrochemical behavior of Co(II), Mn(II), Fe(II), Cu(II), Zn(II), and Ni(II) complexes with di-(2-picolyl)amine ligand L(1) containing antioxidant 2,6-di-tert-butylphenol pendant was studied by cyclic voltammetry (CV), and their radical scavenging properties were examined using the electrochemical DPPH-test. CV curves for these compounds contain the peaks of ligand and metal oxidation/reduction. The possible schemes of redox transformations were proposed. It was shown that the antioxidant capacity of these complexes depends strongly upon their redox properties, and the metal nature plays key role. Thus, the Co(II), Zn(II), and Ni(II) complexes are less active than free ligand. But the easily oxidized Fe(II) complex shows high antioxidant activity which is comparable with the efficiency of the well-known antioxidant Trolox. In this case the synergetic antioxidant effect is observed due to the presence of an essential organic radical scavenger and redox-active metal. The feasible mechanism of antioxidant activity is discussed.