Pyridine Ring Nitrogen Research Articles

Spectral studies of a selenium(IV) vitamin B3 compounds prepared in the form of nanometer using simple chemical reactions to further use as antioxidant in the preparation of drugs

The current study dealt with selenium metal ion complexes with mixed ligands, consisting of nicotinamide (vitamin B3) as the first ligand, and amino acids such as (histidine, tryptophan, and tyrosine) as the second ligand. It was synthesized in (1:1:1) (selenium: vitamin: amino acid) in molar ratio. By using different characterization techniques such as elemental analysis, the conductance, FTIR, XRD, UV-Vis, TG/DTG, 1H-NMR, XRD, SEM, TEM analyses, the chemical structures and the morphological properties of the synthesized complexes were checked and discussed. The nicotinamide was coordinated as monodentate ligand via the nitrogen of pyridine ring but all amino acids as a secondary ligand coordinated as bidentate through oxygen of carboxylic group and nitrogen of amino group. The complexes demonstrate antioxidant activity with potent scavenging property, the synthesized in the form of nanometer give great importance in increasing efficiency of absorption of human cells to selenium giving the highest efficiency of medical product. All complexes in this study were evaluated for their anticancer effect towards HepG2 and A2780 cell lines. From these data the complex (Se/Nia/ Tyr) can be used as antitumor agents. KEY WORDS: Selenium, Amino acids, Vitamin B3, Mixed ligand, Complexes, Antioxidant Bull. Chem. Soc. Ethiop. 2024, 38(6), 1759-1774. DOI: https://dx.doi.org/10.4314/bcse.v38i6.20

Synthesis and Photochemical Characterization of Indolizine Fluorophores Obtained by a Multicomponent Palladium Iodide−Catalyzed Oxidative Aminocarbonylation Approach

AbstractA catalytic carbonylative method for the direct, multicomponent synthesis of indolizine fluorophores has been developed. The process is based on the PdI2/KI‐catalyzed oxidative aminocarbonylation of 2‐(pyridin‐2‐yl)pent‐4‐yn‐1‐carbonyl compounds leading to the corresponding 2‐ynamide intermediates, followed in situ by 5‐exo‐dig cyclization (by amine‐promoted conjugate addition of the pyridine ring nitrogen) and aromatization, to give the finally isolated N,N‐disubstituted 2‐(indolizin‐3‐yl)acetamides. Reactions are carried out under relatively mild conditions (100 °C under 20 atm of a 4 : 1 mixture CO−air for 6–15 h) in MeCN as the solvent and with a low catalyst loading (0.33 mol% PdI2), in the presence of 0.5 equiv. of KI and 3 equiv. of a secondary amine. The optical properties of representative 2‐(indolizin‐3‐yl)acetamide products have also been investigated.

L-Proline catalyzed multi-component synthesis of N-pyridyl-tetrahydroisoquinolines and their α-C(sp3)-H oxygenation.

Herein, we report an effective multi-component synthesis that starts with readily available starting materials and accesses poly-substituted pyridine derivatives by using L-proline as a benign catalyst. This process uses cyclic amines, aldehydes, and malononitrile in a condensation reaction to produce a variety of pyridine derivatives under mild conditions. Furthermore, depending on the catalysts used, the selective synthesis of an amide and/or an aldehyde functionality is achieved through α-C(sp3)-H oxygenation of the tertiary amine moiety in the resultant pyridine derivatives. The pyridine ring's nitrogen atom plays a crucial role in accelerating C-H oxygenation at the α-position of the tertiary amine, highlighting the synthetic versatility and usefulness of this method.

Spectroscopic studies, antimicrobial activity, and computational investigations of hydrazone ligands endowed metal chelates

Our current efforts are aimed to synthesize 16 complexes of Co (II), Ni (II), Cu (II), and Zn (II) metal ions from heterocyclic hydrazone ligands by condensation reaction of 2,6‐diacetylpyridine with hydrazide derivatives to find out combating agent against microorganism diseases. The synthesized compounds were precisely characterized by various physicochemical and spectroscopic techniques like FT‐IR, UV–Vis, 1H and 13C NMR, magnetic susceptibility, ESR, mass spectrometry, powder XRD, TGA, and SEM that suggested the octahedral geometry of the complexes coordinating via enolic oxygen atoms, azomethine nitrogen atom, pyridine ring nitrogen atom of the hydrazone ligands, and oxygen atom of water molecule. The thermal stability of the complexes was demonstrated by thermal analysis revealing two‐step decompositions leaving behind metal oxide as an end residue. By using serial dilution method, the compounds (1–20) were tested for in vitro antimicrobial activity against four bacterial and two fungal pathogens. Among all the synthesized compounds, complex 16 was most active against B. subtilis, whereas complexes 13, 14, and 15 were most efficient for C. albicans. Moreover, the biological efficacy of H2L3 (3) ligand and its (13–16) complexes were demonstrated by computational methods like molecular docking, MESP, DFT, and ADMET studies that highlight that complexes have more potency than the ligands and may be employed as effective drug for pathogen‐induced malformations.

2,6‐Di(1H‐tetrazol‐1‐yl)pyridine and its cupric chloride complex

Abstract2,6‐Di(1H‐tetrazol‐1‐yl)pyridine (DTP) was prepared by a four‐stage procedure, including step‐by‐step heterocyclization of both amino groups of 2,6‐diaminopyridine with triethyl orthoformate and sodium azide. According to quantum‐chemical calculations and single crystal X‐ray diffraction data, DTP crystallizes in the form of the thermodynamically most stable conformer and has an almost flat molecular geometry. DTP was found to react with CuCl2 ⋅ 2H2O in ethanol to give the [Cu(DTP)Cl2(H2O)]n complex, which is a 1D coordination polymer, formed at the expense of bridging DTP ligand via the tetrazole ring nitrogen atoms N4. Possible coordination cites in DTP molecule are discussed using the data of quantum chemical calculations. The pyridine ring nitrogen atom of DTP does not participate in the formation of either coordination or intermolecular hydrogen bonds. This is explained by the results of quantum chemical calculations showing that this atom is less basic than N3 and N4 atoms of DTP molecule.

Enhancing Auxiliary-Mediated Native Chemical Ligation at Challenging Junctions with Pyridine Scaffolds.

To expand the scope of native chemical ligation (NCL) beyond reactions at cysteine, ligation auxiliaries are appended to the peptide N-terminus. After the introduction of a pyridine-containing auxiliary, which provided access to challenging junctions (proline or β-branched amino acids), we herein probe the role of the pyridine-ring nitrogen. We observed side reactions leading to preliminary auxiliary loss. We describe a new easy to attach β-mercapto-β-(4-methoxy-2-pyridinyl)-ethyl (MMPyE) auxiliary, which 1) has increased stability; 2) enables NCL at sterically encumbered junctions (e. g., Leu-Val); and 3) allows removal under mildly basic (pH 8.5) conditions was introduced. The synthesis of a 120 aa long peptide containing eight MUC5AC tandem repeats via ligation of two 60mers demonstrates the usefulness. Making use of hitherto unexplored NCL to tyrosine, the MMPyE auxiliary provided access to a head-to-tail-cyclized 21-mer peptide and a His6 -tagged hexaphosphorylated peptide comprising 6 heptapeptide repeats of the RNA polymerase II C-terminal domain.

Synthesis and Characterization of Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes with 2-Carboxy benzaldehyde Aroylhydrazones

A new metal complexes have been synthesized by a reaction of metal compounds contained Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) with two kinds of ligands that are 2-carboxy benzaldehyde 4-methylbenzoylhydrazone(CBMH) and 2-carboxy benzaldehyde picolinoyl hydrazine (CBPH), the ligands (CBMH and CBPH) were prepared by condensation of 2-carboxy benzaldehyde with 4-methylbenzoyl hydrazide or picolinoyl hydrazide, respectively. In fact, complexes[M(L-H)2]. xH2O were characterized by elemental analysis, molar conductance, magnetic susceptibility, and spectral measurements (UV-Vis, IR,). The hydrazones CBMH and CBPH act as monobasic tridentate ligands, in all their complexes. The ligand CBMH coordinated to the metal ions through the azomethine nitrogen, the carboxyl group oxygen, and the amide carbonyl group oxygen atoms, while the ligand CBPH coordinated through the carboxyl group oxygen, the azomethine nitrogen, and the pyridine ring nitrogen atoms. Physico-chemical studies suggest octahedral geometry for all metal(II) complexes.

Effective photodegradation of organic pollutantsin the presence of mono and bi-metallic complexes under visible-light irradiation

The synthesis of new mono and bi-metallic complexes such as Zn (II) and Ag-Zn (II) complexes with organic functional group-based ligand (OFL) presented in the current work along with the exploration of their applicability in the photocatalytic degradation of organic dyes under visible-light irradiation. The Zn (II) complex obtained from organic functional group-based ligands, complexed with the donor atoms such as S and N under solvothermal conditions and Ag-Zn (II) complex formed through Ag ions complexed with pyridine ring nitrogen atom. These Zn(II)-complexes were systematically analyzed using the physicochemical studies and other spectroscopic techniques. From these facts, it is clarified that the complexes show square planar geometry with organic functional group-based ligands coordination via mercapto and azomethine groups. The reported complexes were used for the photodegradation of standard organic dye pollutants used in various textile and food processing industries. The complex [Ag-Zn(DCMPPT)(H2O)(OAc)] shows higher photocatalytic activity than [Zn(DCMPPT)(H2O)] because of the high surface area, low bandgap energy and further visible-light available for the initiation of ●OH radicals. To identify the active species in the photocatalytic process, the mechanism process also reported for the fast photodegradation of organic dye pollutants in the existence of some radical quenchers.

Unraveling the effect of fluorine substitution on the hydrogen bonding interaction in the complexes of fluorosubstituted pyridines and acetic acid

AbstractThe effect of fluorine substitution on the hydrogen bonding interaction in the complexes of fluorosubstituted pyridines and acetic acid was examined through theoretical method. Two types of double hydrogen bonding cyclic structures have been predicted, one with O–H···N and C–H···O interactions and the other with O–H···F and C–H···O interactions. The changes of the hydrogen bonding interactions are visualized by the reduced density gradient (RDG) and bond critical point (BCP) parameters analysis. With increasing in fluorination, the C–H···O bond strength increases, and the O–H···N and O–H···F bond strengths decrease. Although the O–H···N and O–H···F hydrogen bond energies decrease, the bond type has not changed in all of the fluorinated complexes. For the same degree of fluorination complexes, fluorine favors the C–H···O hydrogen bonding interaction through the cooperating of O–H···F and C–H···O hydrogen bonds, although fluorine is a weak hydrogen bond acceptor. The natural population analysis (NPA) and molecular electrostatic potentials (ESP) were adopted to further explore the variation characteristics of hydrogen bond strength. We found that the substituent fluorine atom acts as a role of electron withdrawing. The pyridine ring nitrogen atom and 2‐position fluorine atom become less negative, and the remaining H atom(s) become more electropositive with increasing degree of fluorination. The hydrogen bond strength is correlated with the charge redistribution of the proton H and acceptor (N and F) atoms.

Synthesis, spectral studies and antibacterial activity of iron(III) complexes with hydrazone functionalized ligands: X-Ray structure determination of a novel five coordinate complex containing labile ligands

Iron(III) complexes having general formula FeLCl 2 [where, L = 2-acetylpyridine acetoylhydrazone(APAH), 2-acetylpyridine benzoylhydrazone(APBH), 2-acetylthiophene acetoylhydrazone(ATAH), and 2-acetythiophene benzoylhydrazone(ATBH) ] have been synthesized characterized based on molar conductivity, electronic and IR spectroscopy. The structure of iron(III) complex with APBH ligand is determined using single crystal X-Ray crystallography . The complex crystallizes in monoclinic space group P21/n with a = 7.8490(6) Å, b = 15.1018(11) Å, c = 13.2263(10) Å, α = 90°, β=100.183(3)°, γ = 90°, V = 1543.1(2) Å3 and Z = 4 with central Fe(III) ion coordinated one tridentate APBH ligand. The iron is 5- coordinate binding with one organic (hydrazone) unit and two labile chloride ligands. The hydrazone acts as NNO –tridentate donor system. Iron is coordinated by pyridine ring nitrogen, azomethine nitrogen and benzoyl oxygen atoms and the two chloride ligands bind with metal completing distorted square pyramidal structure. The iron complexes are screened for their anti-bacterial activities against Pseudomonas aureoginos and Bacillus cereus Acetoyl hydrazones show more antibacterial activity than the corresponding benzoyl hydrazones. Functional groups of azomethine carbon are varied. The hydrazones having a methyl/ and pyridine groups show more anti bacterial activity. The complexes show more activity than the ligands.

Structure activity study of S-trityl-cysteamine dimethylaminopyridine derivatives as SIRT2 inhibitors: Improvement of SIRT2 binding and inhibition

Sirtuin proteins are a highly conserved class of nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases. The pleiotropic human isoform 2 of Sirtuins (SIRT2) has been engaged in the pathogenesis of cancer in a plethora of reports around the globe. Thus, SIRT2 modulation is deemed as a promising approach for pharmaceutical intervention. Previously, we reported S-Trityl-l-Cysteine (STLC)-ornamented dimethylaminopyridine chemical entity named STC4 with a significant SIRT2 inhibitory capacity; this was separate from the conventional application of STLC scaffold as a kinesin-5 inhibitor. An interactive molecular docking study of SIRT2 and STC4 showed interaction between Asn168 of SIRT2 and the methyl ester of STC4, that appears to hinder STC4 to reach the selective pocket of the protein unlike strong SIRT2 inhibitor SirReal2. To improve its activity, herein, we utilized S-trityl cysteamine pharmacophore lacking the methyl ester. Nine compounds were synthesized and assayed affording three biopertinent SIRT2 inhibitors, and two of them, STCY1 and STCY6 showed higher inhibitory activity than STC4. These compounds have pronounced anti-proliferative activities against different cancer cell lines. A molecular docking study was executed to shed light on the supposed binding mode of the lead compound, STCY1, into the selective pocket of SIRT2 by interaction of the nitrogen of pyridine ring of the compound and Ala135 of the protein. The outcome of the study exposes that the active compounds are effective intermediates to construct more potent biological agents.

Synthesis and structural characterization of new transition metal complexes of a highly luminescent amino-terpyridine ligand

The synthesis, NMR and UV–Vis spectroscopy measurements and X-ray diffraction analysis of four new metal complexes of the amino terpyridine ligand 4′-[4-(4-aminophenyl)phenyl]-2,2′:6′,2″-terpyridine L, namely [FeL2](ClO4)2 (1), [ZnL2](ClO4)2 (2), [CdL2](ClO4)2 (3) and [PtMe3IL] (4), are reported. The X-ray crystal structures of complexes 1–3 are 1:2 metal:ligand structures with tridentate ligands decorated around the octahedral metal centers. In complex 4, with L in a bidentate coordination mode, the Pt(IV) coordinated methyl and iodine groups form a fac-arrangement. The 1H NMR spectrum of 4 shows three 195Pt-1H resonances for the methyl groups incorporating the fac-arrangement, which confirms the bidentate coordination mode of L in solution. The X-ray crystal structure of L shows a transoid conformation of the pyridine ring nitrogen atoms along the interannular bond in the terpyridine core. Ligand L exhibits a bright blue emission in dichloromethane [fluorescence quantum yield (ΦF) = 68%] and its emission maxima shows significant solvatochromism (461 nm in dichloromethane to 533 nm in N,N-dimethylformamide), while its complexes 2 and 3 are only very weakly emissive and 1 and 4 are found to be non-emissive.

Role of l- and d-Menthol in the Glucuronidation and Detoxification of the Major Lung Carcinogen, NNAL.

Menthol, which creates mint flavor and scent, is often added to tobacco in both menthol and nonmenthol cigarettes. A potent tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is extensively metabolized to its equally carcinogenic metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as (R)- or (S)-NNAL enantiomers. NNAL is detoxified by UDP-glucuronosyltransferase (UGT) enzymes, with glucuronidation occurring on either NNAL's pyridine ring nitrogen (NNAL-N-Gluc) or the chiral alcohol [(R)- or (S)-NNAL-O-Gluc]. To characterize a potential effect by menthol on NNAL glucuronidation, in vitro menthol glucuronidation assays and menthol inhibition of NNAL-Gluc formation assays were performed. Additionally, NNAL and menthol glucuronides (MG) were measured in the urine of smokers (n = 100) from the Southern Community Cohort Study. UGTs 1A9, 1A10, 2A1, 2A2, 2A3, 2B4, 2B7, and 2B17 all exhibited glucuronidating activity against both l- and d-menthol. In human liver microsomes, both l- and d-menthol inhibited the formation of each NNAL-Gluc, with a stereospecific difference observed between the formation of (R)-NNAL-O-Gluc and (S)-NNAL-O-Gluc in the presence of d-menthol but not l-menthol. With the exception of three nonmenthol cigarette smokers, urinary MG was detected in all menthol and nonmenthol smokers, with l-MG comprising >98% of total urinary MG. Levels of urinary NNAL-N-Gluc were significantly (P < 0.05) lower among subjects with high levels of total urinary MG; no significant changes in free NNAL were observed. These data suggest that the presence of menthol could lead to increases in alternative, activating metabolic pathways of NNAL in tobacco target tissues, increasing the opportunity for NNAL to damage DNA and lead to the development of tobacco-related cancers. SIGNIFICANCE STATEMENT: High levels of the major menthol metabolite, menthol-glucuronide, was observed in the urine of smokers of either menthol or nonmenthol cigarettes. The fact that a significant inverse correlation was observed between the levels of urinary menthol-glucuronide and NNAL-N-glucuronide, a major detoxification metabolite of the tobacco carcinogen, NNK, suggests that menthol may inhibit clearance of this important tobacco carcinogen.

Experimental and Theoretical Evaluation of the Structure and Properties of New Stannyl Complexes of Pyridine Amide Ligands

Aims: Penta and tetra coordinated stannyl derivatives of N, N'-Bis(2-pyridyl)pyridine-2,6-dicarboxamide (H2L) and N-(pyridine-2-yl)picolinamide (HL1) have been synthesized. The structure of the complexes has been well established by Sn119 NMR and computational studies (GAUSSIAN 03 suit of programs). MESP and NBO studies have been carried out to understand different binding modes and properties of the complexes as well as ligands. The relative bond strengths have been estimated using the Wiberg bond index analysis.&#x0D; Study Design: Experimental and computational.&#x0D; Place and Duration of Study: Department of Chemistry, University of Rajasthan, Jaipur, 2014.&#x0D; Methodology: The structure of the complexes has been analyzed by IR and NMR. Computational studies (GAUSSIAN 03 suit of programs) have been used to elucidate the structure of the newly synthesized complexes.&#x0D; Results: 119Sn NMR showed a pentacoordinate range for diamide complexes indicating coordination through the nitrogen of central pyridine ring in addition to amide nitrogens and tetracoordinate range for monoamide complexes confirming the formation of the products. The bonding properties have been confirmed by the computational calculations.&#x0D; Conclusion: A series of dialkyl/diphenyl and trialkyl/triphenyl derivatives of organo tin complexes containing amide functionality have been synthesized and their structural characterizations performed by different spectral techniques and computational analysis.

Menthol Inhibits UGT2B10‐catalyzed Detoxification of the Potent Tobacco‐carcinogen, NNAL

Menthol may be added to tobacco products as either naturally occurring L‐menthol or synthesized racemic DL‐menthol and is excreted as a menthol glucuronide (MG). The most potent tobacco carcinogen is 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK). NNK is extensively metabolized to enantiomers [(R) or (S)] of the equally carcinogenic chiral 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol (NNAL). Both (R)‐ and (S)‐NNAL have been shown to be carcinogenic. Detoxification of (R)‐ and (S)‐NNAL through glucuronidation on NNAL's pyridine ring nitrogen (NNAL‐N‐gluc) is primarily mediated by UGT2B10. Menthol has been shown to inhibit NNAL‐N‐gluc formation in human liver microsomes (HLM). The goal of the present study was to elucidate the impact of menthol on NNAL‐N‐gluc formation in vivo. In vitro inhibition assays using HLM or microsomes from UGT2B10 over‐expressing HEK293 cells were performed with racemic (R/S)‐NNAL as substrate with each menthol enantiomer added separately as inhibitor. In vivo data were gathered from analysis of MG, NNAL, and NNAL metabolites from 50 menthol smokers and 50 non‐menthol smokers. Samples were obtained from the Southern Community Cohort Study. Both L‐ and D‐menthol enantiomers were inhibitors of UGT2B10 in vitro with IC50 values of 236 and 202 μM, respectively. In vivo D‐MG levels, when present, were far below the levels of L‐MG observed in smokers of both menthol or non‐menthol cigarettes, with D‐MG comprising an average of 1.3% of total MG. Urinary L‐MG was detectable in 98 subjects and levels were not significantly different between menthol and non‐menthol smokers (p=0.50). When stratified by tertiles of urinary MG levels, NNAL‐N‐gluc levels were highest in smokers with the lowest MG levels, with NNAL‐N‐gluc levels inversely associated with MG levels in smokers (p&lt;0.05). These data suggest that menthol inhibits a major detoxification pathway of the tobacco carcinogen, NNK. The relatively high levels of urinary menthol in smokers of both menthol and non‐menthol cigarettes raise the possibility that menthol branding may not be the best approach to studying the impact of menthol as a tobacco additive.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Selective Synthesis and Complexation of Novel N,N′‐Alkylene‐Bridged Bis(5‐pyridyltetrazole)

A novel N,N′‐alkylene‐bridged bis(5‐pyridyltetrazole) ligand, namely 2,5‐bis[5‐(2‐pyridyl)‐tetrazol‐2‐yl]‐2,5‐dimethylhexane (bpt), was prepared by regioselective N2‐alkylation of 5‐(2‐pyridyl)tetrazole with 2,5‐dimethylhexane‐2,5‐diol in perchloric acid. The ligand bpt was found to react with copper(II) chloride to give the dinuclear complex [Cu2(bpt)Cl4]. According to single‐crystal X‐ray analysis of the complex, bpt acts as a chelating ligand, coordinated by the metal through the tetrazole ring N4 and the pyridine ring nitrogen atoms. In the complex molecule, two copper atoms are linked by double chlorido bridges, and ligand bpt plays the role of the third bridge. The temperature‐dependent magnetic susceptibility measurements of the complex revealed that the copper(II) ions were weakly antiferromagnetically coupled showing a coupling constant J of –1.04 cm–1.

Selective recognition mechanism of molybdenum(VI) ions binding onto ion-imprinted particle in the water

The recognition mechanism of the ion-imprinted particle for selective recognizing molybdenum ions (IPSR-Mo) in the aqueous phase was studied. The self-selective binding experiment results showed that the best binding pH value for Mo(VI) was similar to the pH value of the imprinting process, and illustrated that the important role of ionic space configurations in selective binding process. Langmuir and Scatchard models showed that the specific recognition sites with high binding affinity were important during the binding process. The selectivity of IPSR-Mo was proved to be perfect in binary and diverse natural water systems. And the selectivity was affected little by the organic matters, but the high concentration cations had more interferences in the water. Finally, XPS were employed to confirm that the nitrogen of pyridine ring was the main imprinting sites and played a crucial role for the selectivity of Mo(VI) binding onto IPSR-Mo. Mo(VI) was bound with two pyridine ring and selectively recognized as an octahedral configuration. This study verified that the ionic space configuration played a key role during the recognition process and provided a new insight into the ion-imprinted particle selective recognition in the water environment.

Synthetic nicotinic/isonicotinic thiosemicarbazides: In vitro urease inhibitory activities and molecular docking studies

Nicotinic and isonicotinic thiosemicarbazide or hydrazine carbothioamides 3–27 were synthesized and the structures of synthetic compounds were elucidated by various spectroscopic techniques such as EI-MS, 1H-, and 13C NMR. Synthetic derivatives were evaluated for their urease inhibitory activity which revealed that except few all derivatives demonstrated excellent inhibition in the range of IC50 values of 1.21–51.42 μM as compared to the standard thiourea (IC50 = 21.25 ± 0.13 μM). Among the twenty-five synthetic derivatives nineteen 1–5, 7, 8, 10, 12, 14–18, 20–22, 24–27 were found to be more active showing IC50 values between 1.13 and 19.74 μM showing superior activity than the standard. Limited structure-activity relationship demonstrated that the positions of substituent as well as position of nitrogen in pyridine ring are very important for inhibitory activity of this class of compound. To verify these interpretations, in silico study was also performed. A good correlation was obtained between the biological evaluation of active compounds and docking study.

Spectral analysis and DFT computations of the hydrogen bonded complex between 2,6-diaminopyridine with 2,6-dichloro-4-nitrophenol in different solvents

New hydrogen bonded complex between 2,6-dichloro-4-nitrophenol (DCNP), proton donor with the proton acceptor 2,6-diaminopyridine (DAP) has been synthesized and characterized in solution and solid state by different spectroscopic techniques. Electronic spectra were used to identify the novel proton transfer complex through appearance of new absorption bands in acetonitrile (CH3CN), methanol (CH3OH) and mixture composed from 1:1 methanol and acetonitrile (AN-Me). The complex stoichiometry was determined to be 1:1 by job's method and photometric titrations. The formation constant was determined by applying minimum-maximum absorbances method where it reached high values confirming the complex high stability. A spectroscopic method for determining DAP was presented and validated statistically. The solid complex was characterized by elemental analysis, infrared and 1H NMR studies where the hydrogen bonded reaction occurs between the phenolic OH with the pyridine ring nitrogen as well as one amino group of DNP. The density functional theory DFT (B3LYP) method has been used to energy optimization of the reactants and complex in the ground state using two basis sets 6-31G(d) and 6–31 G+(d,p). The first one led to energy optimized structure through bifurcated hydrogen bond between OH of DCNP with the ring nitrogen and one amino group of DAP with optimization energy −1998.7 Hartree. The second one gave an optimized structure thought hydrogen bonding between OH and one amino group with lowered optimization energy −2018.1 Hartree. Hence, the experimental results will be simulated with the most stable one at DFT/B3LYB 6-31G+ (d,p). The most reactive electrophilic and nucleophilic sites of DCNP and DAP were predicted using the molecular electrostatic potential. The theoretical electronic spectra in the gas phase and the investigated solvents were calculated at TD-DFT/B3LYP 6-31G+ (d,p) and compared with measured electronic spectra where a satisfactory results have been obtained. An important aim of this work is analysis of the interaction energies between the filled natural bond orbitals (NBOs) and the empty ones in order to shed the light on the ease of electron delocalization among bonds in the novel hydrogen bonded complex.

Nuclear magnetic and nuclear quadrupole resonance parameters of β-carboline derivatives calculated using density functional theory

A density functional theory (DFT) calculations using B3LYP/6-311++G(d,p) method were carried out to investigate the relative stability of the molecules of β-carboline derivatives such as harmaline, harmine, harmalol, harmane and norharmane. Calculated nuclear quadrupole resonance (NQR) parameters were used to determine the 14N nuclear quadrupole coupling constant χ, asymmetry parameter η and EFG tensor (q zz ). For better understanding of the electronic structure of β-carboline derivatives, natural bond orbital (NBO) analysis, isotropic and anisotropic NMR chemical shieldings were calculated for 14N nuclei using GIAO method for the optimized structures. The NBO analysis shows that pyrrole ring nitrogen (N9) atom has greater tendency than pyridine ring nitrogen (N2) atom to participate in resonance interactions and aromaticity development in the all of these structures. The NMR and NQR parameters were studied in order to find the correlations between electronic structure and the structural stability of the studied molecules.