Exocyclic Nitrogen Research Articles

Ringing the Changes: Effects of Heterocyclic Ring Size on Stereoselectivity in [(η5-C5Me5)RhCl], [(η5-C5Me5)IrCl] and [Ru(η6-cymene)Cl] Complexes of Chiral 3-Amino-1-Azacycles.

Ring size-dependent diastereoselective coordination of unsymmetrical diamines containing one azacyclic nitrogen and one exocyclic nitrogen to [(η5-C5Me5)MCl]+ cores where M = Rh, Ir and [Ru(η6-cymene)Cl]+ is reported herein. Total stereoselectivity was observed with the six- and seven-membered azacycles, whereas the five-derivative proved poorly selective. All complexes were active for transfer hydrogenation but showed no enantioselectivity with prochiral ketones.

New expanded porphyrinoids: Synthesis, structure and properties of hemihexaphyrazines and their reduced metal containing derivatives

Hemihexaphyrazines can be considered as hexamembered porphyrinoids of the ABABAB type, where thiadiazole rings (A) and pyrrole-containing subunits (B) joined via aza bridges to form a macrocyclic system with an expanded coordination cavity capable of holding at once three atoms of transition metals that are formed a triangular cluster. It was established for the first time that unsubstituted hemihexaphyrazine and its metal complexes can be reduced to form crystalline salts. These salts were characterized by UV-Vis-NIR and IR spectroscopy, MS, and X-Ray diffraction data. The magnetic properties of these compounds were studied for the first time using EPR and SQUID techniques within the [Formula: see text] K temperature range. It was shown that the three-electron reduction of starting [Formula: see text] yields [Formula: see text] and [Formula: see text] crystalline salts. An unusual doublet-quartet transition was found for the [Formula: see text] dianions. Salt [Formula: see text] also shows an unusually strong low energy NIR absorption, which was observed at 1000–2200 nm with maxima located at 1283 and 1980 nm. A phenomenon consisting of equalization of bond lengths among exocyclic nitrogen atoms ([Formula: see text] and neighboring atoms C(pyrrole) and C(thiadiazole) was observed under reduction conditions.

A safety-catch protecting group strategy compatible with Boc-chemistry for the synthesis of peptide nucleic acids (PNAs).

Peptide Nucleic Acids (PNAs) are an intriguing class of synthetic biomolecules with great potential in medicine. Although PNAs could be considered analogs of oligonucleotides, their synthesis is more like that of peptides. In both cases, a Solid-Phase Synthesis (SPS) approach is used. Herein, the advantage using Boc as a temporal protecting group has been demonstrated to be more favored than Fmoc. In this context, a new PNA SPS strategy has been developed based on a safety-catch protecting group scheme for the exocyclic nitrogen of the side-chain bases and the linker. Sulfinyl (sulfoxide)-containing moieties are fully stable to the trifluoroacetic acid (TFA) used to remove the Boc group, but they can be reduced to the corresponding sulfide derivatives, which are labile in the presence of TFA. The efficiency of this novel synthetic strategy has been demonstrated in the synthesis of the PNA pentamer H-PNA(TATCT)-βAla-OH.

Влияние структурной организации нуклеиновых кислот на взаимодействие с гипохлоритом: АТФP, PolyA и ДНК

The action of hypochlorite on various biological molecules in a living cell has been actively studied for years. However, the influence of the structural organization of nucleic acids on their interaction with hypochlorite remains underinvestigated. In this work, using ultraviolet and infrared spectroscopy, we analyzed the effect of the structure of nucleic acids on the reaction with hypochlorite using the example of the three most common and biologically significant types of nucleic acids (NA): double-stranded DNA in the B-form, single-stranded RNA, and nucleotide phosphates. It was found that the rate of the initial stage of the reaction of hypochlorite with endocyclic nitrogen atoms depends on the presence/absence of base pairing in the NA structure. At the same time, the polymeric structure of NC significantly accelerates and increases the efficiency of the subsequent stages of the reaction associated with the chlorination of exocyclic nitrogen atoms and the destruction of the ring structure of nitrogenous bases.

Mapping H+ in the Nanoscale (A2C4)2-Ag8 Fluorophore.

When strands of DNA encapsulate silver clusters, supramolecular optical chromophores develop. However, how a particular structure endows a specific spectrum remains poorly understood. Here, we used neutron diffraction to map protonation in (A2C4)2-Ag8, a green-emitting fluorophore with a "Big Dipper" arrangement of silvers. The DNA host has two substructures with distinct protonation patterns. Three cytosines from each strand collectively chelate handle-like array of three silvers, and calorimetry studies suggest Ag+ cross-links. The twisted cytosines are further joined by hydrogen bonds from fully protonated amines. The adenines and their neighboring cytosine from each strand anchor a dipper-like group of five silvers via their deprotonated endo- and exocyclic nitrogens. Typically, exocyclic amines are strongly basic, so their acidification and deprotonation in (A2C4)2-Ag8 suggest that silvers perturb the electron distribution in the aromatic nucleobases. The different protonation states in (A2C4)2-Ag8 suggest that atomic level structures can pinpoint how to control and tune the electronic spectra of these nanoscale chromophores.

Molecular structure and biological activities of 4-thiazolidinone derivatives: a combined theoretical and experimental study

In this study, we report the structural and biological characterization of (2Z,5Z)-5-(4-methyl benzylidene)-3-(2-methylpropyl)-2-(phenylimino)-1,3-thiazolin-4-one (6a) and (2Z,5Z)-5-(3-chlorobenzylidene)-3-(2-methylpropyl)-2-(phenylimino)-1,3-thiazolin-4-one (6b). These compounds were synthesized following the reported method and the molecular structures were confirmed by single-crystal X-ray diffraction studies. Density functional theory (DFT) calculation was carried out to complement the structural and spectral features. In vitro cytotoxicity of the compounds was tested against both the cancerous (SW-480 & MCF-7) and normal (HEK-293) cell lines using the MTT assay. The results indicated that compounds adopted (Z,Z)–configuration with respect to the exocyclic methylene proton and the exocyclic nitrogen. It was observed that compound 6a (IC50 = 190 ± 0.23 μg/mL on SW-480 & IC50 = 330 ± 0.27 μg/mL on MCF-7) showed a weaker anti-proliferative effect than 6b (IC50 = 119.87 ± 0.24 μg/mL on SW-480 & IC50 = 140.39 ± 0.28 μg/mL on MCF-7). These compounds showed acceptable toxicity on normal cell line.

Synthesis, Structure and Thermal Properties of Volatile Indium and Gallium Triazenides**

AbstractIndium and gallium nitride are important semi‐conductor materials with desirable properties for high‐frequency and power electronics. We have previously demonstrated high‐quality ALD grown InN and GaN using the hexacoordinated 1,3‐diisopropyltriazenide In(III) and Ga(III) precursors. Herein we report the structural and thermal properties their analogues employing combinations of isopropyl, sec‐butyl and tert‐butyltriazenide alkyl groups on the exocyclic nitrogen of the triazenide ligand. The new triazenide compounds were all found to be volatile (80‐120 °C, 0.5 mbar) and showed very good thermal stability (200 and 300 °C). These new triazenide analogues provide a set of precursors whose thermal properties are determined and can be accordingly tailored by strategic choice of exocyclic nitrogen alkyl substituents.

Zn(II)-isatin-3-thiosemicarbazone complexes with phosphines or diamines for hydrogen storage and anticancer studies

• Novel six zinc(II) mixed ligand complexes of isatin-3-thiosemicarbazone (HITC) and phosphines or diamines were successfully prepared. • The complex [Zn 2 (ITC) 2 µ-(dppm) 2 ]Cl show the ability to store 2.33 wt% of hydrogen. • The complexes showed that the value of cell viability was only 3% for [Zn(ITC)(Bipy)]Cl at a concentration of 400 μM, while it did not exceed 10% for the rest of the tested complexes. Novel six zinc(II) mixed ligand complexes of isatin-3-thiosemicarbazone (HITC) and phosphines or diamines were successfully prepared. These coordination materials were all diagnosed using C.H.N, molar conductivity, FTIR and 1 H, 13 C, 31 P NMR measurements. The analyzes indicated that zinc(II) complexes possess a tetrahedral shape and the ligand (ITC) showed only one coordination mode, negatively charged ITC bounded as a bidentate chelate through the exocyclic nitrogen and the negatively charged sulfur atoms. Four complexes were tested as anti-ovarian cancer, and the results demonstrated that these coordination compounds have a high ability to prevent the growth of tumor cells. The value of cell viability was only 3% for [Zn(ITC)(Bipy)]Cl at a concentration of 400 μM, while it did not exceed 10% for the rest of the tested complexes. Moreover, the hydrogen storage ability of some complexes were examined under different pressures (0–90 bar) at 77 K. The results demonstrate that the complex [Zn 2 (ITC) 2 µ-(dppm) 2 ]Cl 2 is a potential material for storing hydrogen in physical absorption.

Quinolinyl sulfonamides and sulphonyl esters exhibit inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1)

The “superbug” infection caused by metallo-β-lactamases (MβLs) has grown into anemergent health threat, and development of effective MβL inhibitors to restore existing antibiotic efficacy is an ideal alternative. Although the serine-β-lactamase inhibitors have been used in clinical settings, MβL inhibitors are not available to date. In this work, thirty-one quinolinyl sulfonamides 1a-p and sulphonyl esters 2a-o were synthesized and assayed against MβL NDM-1. The obtained molecules specifically inhibited NDM-1, 1a-p and 2a-o exhibited an IC50 value in the range of 0.02–1.4 and 8.3–24.8 μM, respectively, and 1e and 1f were found to be the most potent inhibitors, with an IC50 of 0.02 μM using meropenem (MER) as substrate. Structure-activity relationship reveals that the substitute phenyl and the phenyl with a halogen atom more significantly improve inhibitory effect of quinolinederivatives on NDM-1. 1a-p restored antimicrobial effect of MER on E. coli with NDM-1, EC01 and EC08, resulting in a 2–64-fold reduction in MIC values. Most importantly, 1e synergized MER and significantly reduced the load of EC08 in the spleen and liver of mice after a single intraperitoneal dose. Docking studies suggested that the endocyclic nitrogen of the quinoline ring, and exocyclic nitrogen of the sulfonamide functional group are coordinate with Zn(II) ion at active sites of NDM-1. Cytotoxicity assays indicated that 1e had low cytotoxicity. This work offers potential lead compounds for further development of the clinically useful inhibitor targeting NDM-1.

Excitation of rhodamine 800 in aqueous media: a theoretical investigation.

The main goal of this work was to obtain a calculated absorption spectrum of rhodamine 800 in an aqueous solution, which most accurately reproduces the experimental one. To achieve this result, I used the hybrid functionals supported by Gaussian 16 software package. In this case, the basis set (6-31++G(d,p)) and the solvent model (IEFPCM) were not varied. The B3PW91 functional gave the best agreement with the experimental absorption spectrum of the dye in an aqueous medium. B3P86, B971, B972, B98, X3LYP, APF, HSE06, and N12SX functionals also give good absorption energy coincidence. The B3PW91/6-31++G(d,p)/IEFPCM theory level chosen in this way made it possible to calculate the various characteristics of rhodamine 800 in the ground and excited states. An important result of this work was the establishment of the vibronic nature of the short-wavelength smaller maximum of the absorption spectrum. The influence of the strong H-bond of the exocyclic nitrogen atom with the water molecule on the dye excitation was analyzed.

Hydrogen Storage Capacity and Thermodynamic Calculations of Mercury(II) and Palladium(II) Syn‐2‐Pyridine Aldoxime Complexes

AbstractFour palladium(II) and mercury(II) complexes of the type [MCl2(HPAO)] or [M(PAO)2](HPAO = syn‐2‐pyridine aldoxime) are prepared and characterized using FTIR, 1H NMR spectra, molar conductivity, and melting point. The results demonstrated that a chelating bidentate behavior of APO through the indo and exocyclic nitrogen atoms. The applicability of the prepared complexes in hydrogen storage at a temperature of 77 K and a pressure of 100 bar is studied. The results show that the complexes are capable of storing hydrogen as follows: 1.54, 2.3, 0.53, and 0.63 wt.% of H2 for [Hg(HAPO)Cl2] (1), [Pd(HAPO)Cl2] (2), [Hg(APO)2] (3), and [Pd(APO)2] (4), respectively. Thermodynamic calculations show that the storage type of hydrogen is the physico‐absorption type. The study shows that the central metal has an effect on the ability of the complex to store hydrogen, as the palladium complexes are more capable of storing hydrogen than their mercury counterparts.

Biophysical and Immunological Characterization of Carbamylated-DNA: Serum Autoantibodies of Diabetic Nephropathy Patients Exhibit Strong Binding with Carbamylated-DNA

Isocyanates (ICN) have drawn considerable attention in recent past as they can react with a variety of nucleophiles including DNA, proteins and cause damage(s). However, pathophysiological implications resulting from the occupational and accidental exposures of ICN are yet too elusive. It may be produced in high concentrations in the conditions of chronic renal failure and chronic inflammatory diseases (diabetes mellitus, rheumatoid arthritis, etc.). In this study, mammalian dsDNA was modified with ICN and characterized by UV, fluorescence, FT-IR and thermal melting methods. ICN mainly reacts with exocyclic nitrogen of DNA bases. Antibodies against carbamylated-DNA were raised in rabbits and characterized by direct binding and inhibition ELISA. The presence of anti-carbamylated-DNA autoantibodies in the sera of diabetic nephropathy patients was evaluated by ELISA. Carbamylated-DNA exhibited hyperchromicity at 260 nm and depicted increase in ethidium bromide-assisted fluorescence as compared to the native DNA. Furthermore, the appearance of prominent new peaks in FT-IR profile at different wave numbers suggested carbamoylation-induced changes in the vibration of sugar-phosphate backbone, base(s) etc. Carbamylated-DNA was highly immunogenic as compared to the native DNA. Experimental induction of antibodies against carbamylated-DNA and presence of autoantibodies against carbamylated-DNA in the sera of diabetic nephropathic patients point towards the significance of carbamylated-DNA in diabetic nephropathy.

The influence of exocyclic lone pairs on the bonding and geometry of type A mesoionic rings

Based on structures determined by X-ray crystallography, ab initio MP2 calculations on type A mesoionic rings give geometries in good agreement with observed values. A study of four mesoionic ring systems, each with exocyclic oxygen, nitrogen or carbon groups, shows that the presence and configuration of exocyclic lone pairs significantly influences the geometry and configurational preference. Using a localised bond model and NBO analysis, these effects are rationalised in terms of an anomeric interaction of lone pairs with the antibonding orbitals of adjacent σ bonds. In agreement with experiment, similar effects are calculated for pyran-2-imines.

SYNTHESIS AND BROMINATION OF 2-METALLYLTHIO-3-HYDROXYIMINOMETHYLQUINOLINE

Quinoline and its condensed analogues are an important class of heterocycles with a wide range of biological activity. Many quinoline derivatives are used as substrates in organic synthesis and molecular design of pharmacologically active substances with different effects. Its reported a number of natural compounds containing a quinoline fragment are used as drugs. The annulation of azole and azine heterocycles to the quinoline backbone expands the search for biologically active compounds in this series. The most convenient and most effective method of annulation of additional cycles to quinoline is the reaction of electrophilic intramolecular cyclization of its unsaturated derivatives with various electrophilic reagents. Therefore, the synthesis of previously unknown polycyclic quinoline derivatives is an urgent problem.
 The purpose of this work is to study of the regio-selectivity of the process of electrophilic intramolecular cyclization of 2-methallylthio-3-(hydroxyiminomethyl)quinoline.
 The model oxime was obtained by the condensation reaction of 3-formyl-2-methalylthioquinoline with hydroxylamine hydrochloride in an alcohol-alkaline medium. 2-Methallylthio-3-(hydroxyiminomethyl)quinoline has several nucleophilic centers for studying of the regioselectivity of electrophilic heterocyclization - a multiple bond of a methallyl fragment, an endocyclic nitrogen atom of quinolone cycle, an exocyclic nitrogen atom of an imino group and an exocyclic atom oxygen of ОН- group. During the bromination of such an oxime, the formations of both a linear and angular tricyclic system are possible. It was found that when brominated with a double excess of bromine in chloroform medium, the thiazole cycle is annealed to the quinoline backbone to form 1-bromomethyl-4-((hydroxyimino)methyl)-1-methyl-1,2-dihydrothiazolo[3,2-a]-quinolin-10-ium tribromide.
 Thus, as a result of the performed research, the 2-methallylthio-3-(hydroxyiminomethyl) quinoline was obtained and its bromination was carried out. It is proved that the bromocyclization of the model oxime occurs regio-selectively with the formation of angular tribromide of 1-bromomethyl-4 -((hydroxyimino)methyl) -1-methyl-1,2-dihydrothiazolo [3,2-a] quinolin-10-ium. This tricyclic salt has the potential to have high biological activity.

OBTAINING AND RESEARCH OF PALLADIUM COMPLEXES WITH 4-AMINOPIRIDINE

The obtaining and investigation of various complex compounds of the biologically active aromatic heterocyclic ligands with platinum and palladium are of interest due to their potential medical applications. To that end, 4-amino pyridine containing cyclic and exocyclic nitrogen atoms has been used. The main aim of this work is to clarify which nitrogen atom of the ligand composes stronger and more stable bond. As a result of IR-spectroscopic investigation of synthesized complexes, the acquired information demonstrated that the pyridine nitrogen atom of the ligand is protonated and composes outer sphere as monocharged cation. However, tetraacidoanion is formed in the inner sphere. In the alkaline medium the ligand is monodentately coordinated with palladium through nitrogen atom of pyridine. The exocyclic nitrogen atom of the ligand does not participate in the coordination regardless of pH of the medium and stoichiometric ratio of the taken compounds The initial biological probes were accomplished and the correlation between their biological activities, composition and structures of complexes were determined.

Obtaining and Research of Palladium Complexes with 4-aminopiridine

The obtaining and investigation of various complex compounds of the biologically active aromatic heterocyclic ligands with platinum and palladium are of interest due to their potential medical applications. To that end, 4-amino pyridine containing cyclic and exocyclic nitrogen atoms has been used. The main aim of this work is to clarify which nitrogen atom of the ligand composes stronger and more stable bond. For that purpose, the synthesis of palladium salts with ligand has been accomplished within a wide interval of pH (3-12) and temperature (50-800C). The cation-anion and neutral complex compounds have been obtained depending on stoichiometric ratio of the reacting components, temperature and pH and was further studied. As a result of IR-spectroscopic investigation of synthesized complexes, the acquired information demonstrated that the pyridine nitrogen atom of the ligand is protonated and composes outer sphere as monocharged cation. However, tetraacidoanion is formed in the inner sphere. In the alkaline medium the ligand is monodentately coordinated with palladium through nitrogen atom of pyridine. The exocyclic nitrogen atom of the ligand does not participate in the coordination regardless of pH of the medium and stoichiometric ratio of the taken compounds. As a result of investigation of the thermal stability of the complexes it was determined that the neutral complexes are decomposed without melting at higher temperature than cation-anion complexes. It has been found that one of the factors that affects thermal stability is the steric structure of the complexes. The initial biological probes were accomplished and the correlation between their biological activities, composition and structures of complexes were determined. Despite the fact of taking the same medium and ligand, the cation-anion complexes indicate completely different biological activities than neutral ones.

Synthesis of 5-arylmethylidene-3-(arylmethylideneamino)thiazolidine-2,4-diones via triazine ring cleavage of tetrahydroimidazothiazolotriazinediones and their reactions with azomethine ylides

Cleavage of 1,3-dimethyl-3,3a,9,9a-tetrahydroimidazo[4,5- e ]thiazolo[3,2- b ][1,2,4]triazine-2,7(1 H ,6 H )-diones upon treatment with aromatic aldehydes has been shown to afford ( Z )-5-arylmethylidene-3-(( E )-arylmethylideneamino)thiazolidine-2,4-diones bearing two identical or different arylmethylidene fragments at the exocyclic nitrogen atom and at position 5 of thiazolidine cycle. 1,3-Dipolar cycloaddition reaction of thiazolidine-2,4-dione derivatives with azomethine ylide generated from isatin and sarcosine gave diastereomerically pure dispiro[indole-3,2'-pyrrolidine-3',5''-thiazolidine]-2,2'',4''-triones in good yields. Dispiro compound with two 4-methoxyphenyl fragments exhibited slight antiproliferative activity toward CCRF-CEM (leukemia) and CAKI-1 (renal cancer) cell lines.

Induction of the SOS response of Escherichia coli in repair-defective strains by several genotoxic agents

DNA is exposed to the attack of several exogenous agents that modify its chemical structure, so cells must repair those changes in order to survive. Alkylating agents introduce methyl or ethyl groups in most of the cyclic or exocyclic nitrogen atoms of the ring and exocyclic oxygen available in DNA bases producing damage that can induce the SOS response in Escherichia coli and many other bacteria. Likewise, ultraviolet light produces mainly cyclobutane pyrimidine dimers that arrest the progression of the replication fork and triggers such response. The need of some enzymes (such as RecO, ExoI and RecJ) in processing injuries produced by gamma radiation prior the induction of the SOS response has been reported before. In the present work, several repair-defective strains of E. coli were treated with methyl methanesulfonate, ethyl methanesulfonate, mitomycin C or ultraviolet light. Both survival and SOS induction (by means of the Chromotest) were tested. Our results indicate that the participation of these genes depends on the type of injury caused by a genotoxin on DNA.

Tautomerism of N-substituted acridin-9-amines in the context of dynamic NMR and matrix isolation-FT-IR spectroscopy supported by DFT calculations and structural analysis

The physiochemistry of acridin-9-amines (A9As) is an issue that has been investigated by many research groups, due to their intriguing structural and spectroscopic properties as well as their applications in medicine as anticancer, antibacterial and other drugs.In this work we undertake the problem of prototropic tautomerism among simple A9As, substituted at the amine (exocyclic) nitrogen atom with alkyl, acetyl, and phenyl groups, analysed with respect to derivatives of retained amine or imine structure as well as acridin-9-amine itself − the parent compound in this group. Advanced approaches were applied to assess crucial physicochemical features of such compounds, that can be treated as model molecular systems for more advanced drugs − in the context of their potency to tautomerise at various environments.The purity and chemical identity of acridin-9-amines synthesised for this study was confirmed by classical methods (TLC, LC, melting point determination, elemental analysis, typical 1H NMR), and the structure of some A9As in a crystalline solid phase previously assessed was analysed comparatively. The spectroscopic features of investigated acridin-9-amines, assessed by dynamic nuclear resonance spectroscopy (1H and 13C NMR; temperature-dependent spectra) as well as infrared spectroscopy (FT-IR) combined with matrix isolation (MI), are mainly addressed in this work. The above techniques enabled us to obtain their unique spectral characteristics and to confirm experimentally the existence of tautomerism among simple derivatives of acridin-9-amine − not previously investigated applying such approaches.Density functional theory (DFT) was employed to get deeper insight into tautomerisation ability and determine the thermodynamic characteristics such as relative energies, molecular geometry, and atomic charges, characterising studied group of acridin-9-amines. Theoretical data generally remains in agreement with the experimental results and allowed an assessment of how far the N-substitution of A9As has an impact on the tautomerisation process, including the population of specific forms in the equilibrium in various environments.

Phosphoramidates as Steering Elements for Highly Selective Access to Complementary Imidazo[1,2-a]pyrimidine Isomers.

We report that selective N-phosphorylation of aminoimidazoles results in a key steering element that controls isomeric selectivity in the condensation of β-ethoxy acrylamides and aminoimidazoles to furnish imidazo[1,2-a]pyrimidines. We identified conditions that provide highly selective (99:1) phosphorylation at the endo- or exocyclic nitrogen. Either the 2-amino or 4-amino isomer of the (benzo)imidazo[1,2-a]pyrimidine products could be isolated in 64-95% yield. Mass spectrometric analysis and computational studies give insight into the mechanism of this exceptionally selective transformation.