Cyclic Nitrogen Atoms Research Articles

QSAR and docking based lead optimization of nitrogen heterocycles for enhanced prostaglandin EP2 receptor agonistic potency

In the existing effort, a dataset of 309 experimentally screened molecules for in vitro (Ki) agonist potential for Prostaglandin E2 (PGE2) receptor 2 subtype (EP2), which is a metabolite of arachidonic acid that binds with and regulates cellular responses to PGE2, was investigated in the QSAR (Quantitative structure–activity relationship) study. A six-parameter QSAR model was developed that meets the specified values ​​for internal and external validation as well as random parameters such as R2tr = 0.808, Q2LMO = 0.794, R2ex = 0.781. Insightful and quantitative opinion reveals several underappreciated and distinct structural features that are responsible for the agonist potency of these molecules on Prostaglandin EP2 receptor such as; the hydrogen atom is correct 2 bonds from the donor atom, the sp2 hybridized carbon atom is correct 2 bonds from the cyclic nitrogen atom, and so on. The developed QSAR model captures the narrative as well as the novel pharmacophoric features. The QSAR effect was further demonstrated using the reported crystalline buildings of CP533536 with the Prostaglandin EP2 receptor activity. The evaluation led to the identification of valuable new pharmacophoric properties that will be used to optimize lead compounds in the future.

Novel Strigolactone Mimics That Modulate Photosynthesis and Biomass Accumulation in Chlorella sorokiniana.

In terrestrial plants, strigolactones act as multifunctional endo- and exo-signals. On microalgae, the strigolactones determine akin effects: induce symbiosis formation with fungi and bacteria and enhance photosynthesis efficiency and accumulation of biomass. This work aims to synthesize and identify strigolactone mimics that promote photosynthesis and biomass accumulation in microalgae with biotechnological potential. Novel strigolactone mimics easily accessible in significant amounts were prepared and fully characterized. The first two novel compounds contain 3,5-disubstituted aryloxy moieties connected to the bioactive furan-2-one ring. In the second group of compounds, a benzothiazole ring is connected directly through the cyclic nitrogen atom to the bioactive furan-2-one ring. The novel strigolactone mimics were tested on Chlorella sorokiniana NIVA-CHL 176. All tested strigolactones increased the accumulation of chlorophyll b in microalgae biomass. The SL-F3 mimic, 3-(4-methyl-5-oxo-2,5-dihydrofuran-2-yl)-3H-benzothiazol-2-one (7), proved the most efficient. This compound, applied at a concentration of 10-7 M, determined a significant biomass accumulation, higher by more than 15% compared to untreated control, and improved the quantum yield efficiency of photosystem II. SL-F2 mimic, 5-(3,5-dibromophenoxy)-3-methyl-5H-furan-2-one (4), applied at a concentration of 10-9 M, improved protein production and slightly stimulated biomass accumulation. Potential utilization of the new strigolactone mimics as microalgae biostimulants is discussed.

8-Bromo-4,5-bis(dimethylamino)quinoline: Synthesis, protonation, and the first structural studies of quinoline “proton sponge” as a base

Synthesized 8-bromo-4,5-bis(dimethylamino)quinoline is the simplest and at the same time the first representative of quinoline “proton sponges”, existing as a base in a crystalline form, and not as an oil. This allowed to perform the XRD study both for the title compound and its salt with HBF4. The results obtained revealed a significant conjugation of the cyclic nitrogen atom with peri-NMe2 groups, which initiates a noticeable planarization of the latter and lengthening the distance between them. As a result, the mono-protonated salts of the title quinoline, either in solid or in solution, exist completely in the quinolinium form. To compare the effect of peri-NMe2 groups on the stability of naphthalene and quinoline proton sponges, the structural index of their aromaticity was calculated for the first time.

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.

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.

Thiazolidine-2,4-dione in benzoylation reaction

The direction of the benzoylation reaction of thiazolidine-2,4-dione under the conditions of basic and general acid catalysis was studied. It was shown that the direction of benzoylation of thiazolidine-2,4-dione at the cyclic nitrogen atom or oxygen atoms depends on two major factors: the solvent and the presence of cations. A nonpolar solvent and triethylamine direct the reaction toward the formation of the dibenzoyl product, which was isolated and characterized for the first time. The structure of this compound has been unambiguously identified using NMR and X-ray diffraction analysis. A hydrogen bond between the nitrogen atom of the dibenzoyl product and the proton of the chloroform molecule was found in crystal structure.

Synthesis, characterization and anticancer activity of new zinc(II), molybdate(II), palladium(II), silver(I), rhodium(III), ruthenium(II) and platinum(II) complexes of 5,6-diamino-4-hydroxy-2-mercaptopyrimidine

New complexes of 5,6-diamino-4-hydroxy-2-mercaptopyrimidine (Hdahmp), [Zn(Hdahmp)2Cl2], [Zn(bpy)(dahmp)]Cl, [Zn(Hdahmp)2]SO4, [Pd(Hdahmp)(dahmp)]Cl, [Pt(dahmp-H)]+n, [M(bpy)(dahmp]Cl, [M(bpy)(Hdahmp]Cl2 (M(II)=Pd, Pt), [Ru(dahmp)2(PPh3)2], [Rh(dahmp)2(H2O)2]Cl, [Ag2(Hdahmp)2], cis-[MoO2(dahmp∗3HCl)2] and cis-[MoO2(Hdahmp)(DMF)Cl]Cl have been synthesized and characterized on the basis of elemental analyses, IR, NMR (1H, 13C, 31P), UV–Vis and ESI-mass spectrometry, thermal and molar conductivity measurements. 5,6-Diamino-4-hydroxy-2-mercaptopyrimidine exhibits five different modes of chelation: (i) a neutral bidentate ligand through the cyclic nitrogen (N-3) and thione sulfur atoms, (ii) a mononegative bidentate ligand through the deprotonated cyclic nitrogen (N-1) and thione sulfur atoms, (iii) a mononegative bidentate ligand through the cyclic nitrogen (N-3) and deprotonated hydroxy centers, (iv) a tetradentate ligand through the cyclic nitrogens (deprotonated N-1, N-3), thione and deprotonated hydroxy oxygen centers, and (v) a mononegative bidentate through the deprotonated cyclic nitrogen (N-3) and ketonic oxygen atoms. The free Hdahmp and several of its complexes have been tested against the human serous ovarian cancer (OV-90) and human ovarian cancer (OVCAR-8) cell lines.

Bone Repair Stimulation in Rat Mandible by New Chitosan Silver(I) Complexes

Two new chitosan silver(I) complexes, [Ag(2CS)(H2O)(NO3)] and [Ag(2CS)(ahmp)(H2O)] (CS = chitosan, Hahmp = 4-amino-6-hydroxy-2-mercaptopyrimidine) were synthesized and characterized on the basis of elemental analysis, spectral (FT-IR and solid-state 13C-NMR), morphological (SEM, matrix analysis, XRD, and XRPE), and thermal measurements. Chitosan behaves as a neutral ligand, coordinates Ag(I) through half of amino nitrogen centers, with the pendant glucose amine hydroxy functionality playing no role in coordination, while 4-amino-6-hydroxy-2-mercaptopyrimidine functions as mononegative bidentate, chelating through the deprotonated cyclic nitrogen and thione sulfur atoms. [Ag(2CS)(ahmp)(H2O)] displays a significant potential bone regenerator in rat mandible. Forty male rats were divided into two groups: bone defect (control) and bone defect with [Ag(2CS)(ahmp)(H2O)] (treated). The bone defects were stained with hematoxylin and eosin, and Masson's trichrome for histological analysis. The treated group shows faster and well organized bone formation in the defect in comparison to the control group which shows little new bone trabeculae and wide marrow cavities.

New zinc(II), palladium(II) and platinum(II) complexes of dl-piperidine-2-carboxylic acid; X-ray crystal structure of trans-[Zn2(μ-Ca)2(Hpa)2Cl6] and anticancer activity of some complexes

New complexes of dl-piperidine-2-carboxylic acid (dl-H2pa), [Zn(Hpa)(AcO)(H2O)2], trans-[Zn2(μ-Ca)2(Hpa)2Cl6], [M(bpy)(Hpa)]Cl and [M(pa)(PPh3)2] (M(II)=Pd, Pt) have been prepared and characterized on the basis of elemental analyses, molar conductivity and thermal measurements, IR, Raman, UV–Vis, NMR (1H and 31P) and mass spectroscopy. dl-Piperidine-2-carboxylic acids act as bidentate ligands, through the carboxyl oxygen and cyclic nitrogen atoms. The crystal structure of trans-[Zn2(μ-Ca)2(Hpa)2Cl6], obtained from the addition of ZnCl2 to dl-H2pa in either hard tap water or presence of CaCl2, has been determined by X-ray diffraction. It crystallizes in a triclinic lattice with space group symmetry P1. The complex has two zinc atoms in tetrahedral geometry, each ligated by a carboxyl oxygen and three chlorine atoms. The other carboxyl oxygen atoms from the two Hpa− ligands are bridged by two calcium atoms, i.e., there are two Zn(Hpa−)Cl3 units bridged by two calcium atoms. The free dl-H2pa and its complexes, trans-[Zn2(μ-Ca)2(Hpa)2Cl6], [Pd(bpy)(Hpa)]Cl and [M(pa)(PPh3)2] (M(II)=Pd, Pt) have been tested against the serous ovarian cancer ascites, OV 90 cell line.

Synthesis, structural characterization and anticancer activity of some new complexes of 6-amino-4-hydroxy-2-thiopyrimidine

New complexes of 6-amino-4-hydroxy-2-thiopyrimidine (Hahtp), [Zn(ahtp)2(H2O)2], [Zn(ahtp)2(PPh3)(H2O)], [Zn(Hahtp)(bpy)Cl2], [Pd(phen)(ahtp]Cl, [Pd(Hahtp)(PPh3)2]Cl2, [Ag(ahtp)(H2O)2], [Ag(ahtp)(PPh3)(H2O)], [Ag(ahtp)L] (L=bpy, phen), have been synthesized and characterized on the basis of spectral (IR, 1H-NMR, ESI-mass and UV–visible), elemental analysis, thermal and molar conductivity measurements. Three modes of chelations have been observed for Hahtp; as a neutral bidentate ligand through cyclic nitrogen and thione sulfur atoms, mononegative bidentate ligand through either the deprotonated cyclic nitrogen and thione sulfur atoms or the deprotonated hydroxy and cyclic nitrogen atoms; all forming four-membered chelating rings. The free Hahtp and its complexes, [Zn(ahtp)2(H2O)2], [Zn(Hahtp)2(PPh3)(H2O)], [Zn(Hahtp)(bpy)Cl2], [Pd(phen)(Hahtp]Cl and [Ag(Hahtp)(PPh3)(H2O)] have been tested against the human breast cancer MDA-MB231 cell line. The [Ag(ahtp)(PPh3)(H2O)] complex exhibits the highest efficacy with a mean IC50 value of 4.7μM.

Theoretical and experimental investigations of photophysics of the nile red molecule and its protonated structures

Results of quantum-chemical studies of the nile red (NR) molecule and its protonated structures by the INDO/S method are presented. It is demonstrated that the best agreement between the calculated and experimental data is obtained for the flat molecule in the ground electron state. Energies of the strongest singlet and triplet electronic states, molecular nature of these states, transition oscillator force, dipole moments in the ground and excited states, electron density distribution around atoms and molecular fragments in the S0 and S1 states, and rate constants of radiative, internal, and intercombination conversion are presented for the NR molecule and its protonated structures. The most probable NR protonation centers are analyzed using the molecular electrostatic potential (MESP) method. It is established that the reaction of proton addition to the NR molecule proceeds at the cyclic nitrogen atom. As demonstrated the results of quantum-chemical calculations, low fluorescent properties of the protonated NR structures (with a quantum yield of 4%) are due to a high rate of the S1 – T4 intercombination conversion.

Synthesis and properties of cross-conjugated ω,ω′-bis-dimethylamino ketones and dinitriles with N-acetyl- and N-benzylpiperidine cycles

Reactions of N-acetyl- and N-benzyl-4-piperidones with aminal of β-dimethylaminoac-rolein yielded ketocyanines bearing piperidine cycle. Reaction of 3-dimethylamino-1,1,3-trimethoxypropane with 1-acetylpiperidin-4-ylidenemalononitrile in the presence of ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4), resulted in cross-conjugated ω,ω’-dimethylamino dinitrile. Protonation of ketocyanines bearing N-acetyl- and N-benzyl-piperidine cycles with Et2O·HBF4 (1 equiv.) furnished piperidinium salts, while protonation of the latter with Et2O·HBF4 (2 equiv.) afforded doubly charged 4-hydroxypolymethine salts. Unlike protonation, reaction of 3,5-bis(3-dimethylaminoprop-2-enylidene)-1-acetylpiperidin-4-one with Me2SO4 involved only the oxygen atom and led to a singly charged 4-methoxypolymethine salt. Methylation of 3,5-bis(3-dimethylaminoprop-2-enylidene)-1-benzylpiperidin-4-one with Me2SO4 (1 equiv.) involved cyclic nitrogen atom and resulted in piperidinium salt; heating of the latter with the excess of Me2SO4 afforded doubly charged bis-methoxysulfonate. Starting from 4-methoxytetrahydropyridinium salts, meso-methoxythiapentacarbocyanine dyes were synthesized.

Phosphorus–nitrogen compounds: part 16. Synthesis, stereogenism, anisochronism and the relationship between 31P NMR spectral and crystallographic data of monotopic spiro-crypta phosphazene derivatives

The condensation reactions of N2O3-donor type coronands (1–3) with hexachlorocyclotriphosphazatriene, N3P3Cl6, resulted in the formation of spiro-crypta phosphazene derivatives (4–6). These compounds with excess morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD) afford fully substituted morpholino (7 and 10) and 1,4-dioxa-8-azaspiro[4,5]deca (8)-substituted phosphazene derivatives, respectively. Whilst, in the same conditions, the reactions of 4, 5 and 6 with pyrrolidine, morpholine and DASD also produce partially pyrrolidino-substituted geminal (9 and 11), mono-substituted pyrrolidino (12), morpholino (13) and 1,4-dioxa-8-azaspiro[4,5]deca (14) phosphazenes. It has been clearly observed that the chloride replacement reactions of 4, 5 and 6 with pyrrolidine lead to the geminal products. Compounds 7, 8 and 10 are the first examples of anisochronic tetrakis (amino) phosphazenes according to 31P NMR data. The structures of 7, 8 and 10–14 have been determined by FTIR, MS, 1H, 13C and 31P NMR, DEPT, and HETCOR spectral data. The solid-state structures of 9, 13 and 14 have been examined by X-ray diffraction techniques. The sums of the bond angles around the spiro cyclic nitrogen atoms [344.8(4)° and 347.6(4)°] of 9, indicate that the nitrogen atoms have pyramidal geometries. Thus, the N atoms seem to have stereogenic configurations. Compounds 12–14 also have two stereogenic P-atoms, and they are expected to be in the mixture of enantiomers. The relationships between NPN (α and α′) bond angles and δPspiro values and the correlation of Δ(P–N) with δPspiro and Δ(δP) values are presented.

Diphenylmethyl Protective Group in the Synthesis of 5-Substituted 3-Nitro-1H-1,2,4-triazoles

A diphenylmethyl protective group is suggested for use in the synthesis of 5-R-3-nitro-1H-1,2,4-triazoles unsubstituted at the cyclic nitrogen atom, via nucleophilic substitution of 5-bromo- and 5-methylsulfonyl groups.

Nucleophilic substitution of hydrogen in the reaction of 1,2,4-triazin-4-oxides with cyanamide

It was shown that cyanamide can successfully be used in reactions of nucleophilic substitution of hydrogen with 1,2,4-triazin-4-oxides in the presence of a base to give 5-cyanoimino-1,2,4-triazines. It was found by13C NMR spectroscopy that these compounds and their alkylation products at the cyclic nitrogen atom exist in the form of 5-cyanoimino-2,5-dihydro-1,2,4-triazines.

Revisión estructural de agentes químicos que pueden inducir parkinsonismo

To identify similar structural elements in the largest number possible of chemical agents which can induce Parkinsonism and study their relation with the main chemical changes seen in Parkinsonism. We studied the chemical structure and structural relations of the chemical agents reported in the literature because of their ability to induce Parkinsonism. We observed the structural similarity of the majority of chemical agents and the structural discrepancy of the rest. The structural element identified as common had three clearly differentiated parts: a cyclic fragment, bridge fragment and nitrogen atom fragment. We studied the diversity of the parts of each fragment. We studied the relation of the common structural element with other biochemical components which are altered in Parkinsonism, and also the possible mechanism of action of the structural element in the process of induction of Parkinsonism. There is a structural grouping close to the molecule of the dopamine neurotransmitter in most of the organic compounds which can induce Parkinsonism. Therefore, we suggest that the origin of certain Parkinsonian conditions may be due to changes in the natural equilibrium of dopamine due to the action of chemical agents with a suitable chemical substructure similar to that of dopamine.

Identification of the 1,3,2,4-Dithiadiazolyl RCNSNS(*) Radical Dimers in Solution, Their Dimeric Concerted Photochemically Symmetry-Allowed Rearrangement to 1,2,3,5-Dithiadiazolyl RCNSSN(*) by the Net Exchange of Adjacent Cyclic Sulfur and Nitrogen Atoms, and the Photolysis of RCNSNS(*).

The 1,3,2,4-dithiadiazolyl RCNSNS(*) radicals undergo an unprecedented concerted rearrangement to the thermodynamically more stable 1,2,3,5-dithiadiazolyl RCNSSN(*) radicals by the net exchange of adjacent cyclic sulfur and nitrogen atoms. The UV-visible spectra of RCNSNS(*) (R = Ph, p-O(2)NC(6)H(4), 3,5-(O(2)N)(2)C(6)H(3), CF(3)) in solution show bands at 250 nm (strong) and 680 nm (very weak) attributable to monomer and two dimer bands at 376 and 480 nm, the positions of which are independent of the substituents, providing direct identification of the radical dimers in solution. The dimerization equilibrium constant (K(298) approximately 0.7 for R = Ph) at room temperature was derived from the enthalpy and entropy changes for the dimerization of PhCNSNS(*) (DeltaH(d) degrees = -19.0 kJ/mol, DeltaS degrees = -66.5 J/mol) estimated by a variable-temperature ESR spectroscopic study. In addition, RCNSNS(*) (R = Bu(t), Ph) undergo an apparent unimolecular photolysis to RCN and possibly SNS(*) (analogue of ONO(*)). The photochemical rearrangement and dissociation (for R = Ph and 3,5-(O(2)N)(2)C(6)H(3)) were shown to proceed by irradiation of the radical dimer (376 and 480 nm) and monomer (250 nm), respectively. Thus, the radical rearrangement reasonably occurs via a concerted dimeric pathway shown by molecular orbital calculations (CNDO) to be photochemically symmetry-allowed. In addition, we propose that the radical dissociation proceeds via a concerted unimolecular photochemically symmetry-allowed process.

Biological activity of some heterocycles containing the CF 3 − group

The modification of the structures of biologically active compounds by means of hydrogen atom substitution by fluorine or perfluoroalkyl groups leads rather often to an increase in their biological activity and selectivity. We have synthesized some heterocycles ( 1–3) containing the CF 3-group on the cyclic carbon atom and an alkyl group on the cyclic nitrogen atom. 1,1,1-trifluoro-2-bromopropene has been used as the starting material. ▪ The investigation of the biological activity of 1–3 shows that thionthiazolidine ( 1) and imino-thiazolidine ( 2) possess quite significant radioprotective activity and rather small toxicity. Among the trifluoromethylated aziridines ( 3) several compounds with fungicide activity have been found.

Nuclear quadrupole resonance in nitro compounds

Nitro groups are characterized by NQR lines of low intensity, since they lie in the 0.5-1 MHz frequency range. For example, in the cases of 1,3,5,7-tetranitro-l,3,5,7-tetraaxacyclooctane and cyclotrimethylenetrinitramine [i0, ii], it was not possible to detect the NQR spectra of the nitro groups with the aid of direct pulse NQR. Nevertheless, 14N NQR lines for the cyclic nitrogen atoms in these compounds were observed at 289 K at frequencies equal to 5300, 5063, 3737, and 3623 kHz and at 5192 and 3410 kHz (the most highfield lines). These lines are sufficiently intense to be observed in industrial mixtures of the compounds indicated with trinitrotoluene. With the aid of the spiral surface of the coil, direct pulse NQR [3] makes it possible to obtain a noticeable 14N signal from 1 kg of a mixture at distances up to 20 cm, even if the sample is located underground[2].