Secondary Amine Nitrogen Research Articles

β-Enaminones and organic salts from 3-benzoyl-4‑hydroxy-6-phenyl-2H-pyran-2-one: Synthesis, X-ray crystal structural studies and antimicrobial activity

The reactivity of pyran-2,4‑dione 1 towards primary amines (propylamine and p-toluidine) and secodary amines (morpholine and piperidine) were investigated. The reactions were proceeded by replacement of the external alcoholic hydroxyl group with primary amine accompanied by loss of water molecule to give β-enamino-pyran-2,4-diones 2 and 3. In case of secondary amines, a transfer of the phenolic proton of pyrone ring to the secondary amine nitrogen leading to the formation of the corresponding quaternary ammonium salts of morpholine 4 and piperidine 5, respectively. The X-ray single crystal structures of 2 and 4 proved with no doubt the proposed structure based on the spectral characterization. The percentages of the H…H, O…H, and C…H interactions are in the range of 49.2–50.6 %, 19.6–19.8 and 27.6–28.6 %, respectively in case of 2 based on Hirshfeld topology analysis. For the two cationic units in 4, the C…H (15.9–18.5 %), H…H (42.9–43.1) and O…H (38.2–40.5 %) are the most important. The two anionic units showed different types of intermolecular interactions. In one unit, the O…H (23.4 %), C…H (28.4 %) and C…C (1.3 %) contacts are the most important while in the other anionic unit the O…H (23.3 %), C…H (26.7 %), C…O (5.7 %) and C…C (1.6 %) interactions are the most significant. The inhibition zones of 1 (18 mm), 4 (22 mm), and 5 (20 mm) indicated greater activity against S. aureus, compared to streptomycin (16 mm) and neomycin (13 mm). Compounds 1–5 showed nearly two-fold as much antifungicidal activity against C. albicans compared to some conventional medicines such as Neomycin and Streptomycin.

Mechanistic Insights into the Appel Reaction Mediated by a Poly-Phosphamide Material as a Heterogeneous Catalyst.

Due to notable thermochemical stability, polyphosphamides are often regarded as flame retardants, while molecular phosphamides can serve as versatile Lewis base to catalyze diverse organic transformations. Being chemically analogous to phosphine oxide, phosphamide can also be considered as a mediator for the phosphine-mediated reaction. Herein, an amorphous polymeric material consisting of phosphamide (-NH-P(O)) in the repeating unit (POP) has been prepared via condensation of tris(2-aminoethyl)amine (TREN) and phenyl phosphinic dichloride (PPDC). The POP is isolated as a metal-free and pure organic material which is made of a strong covalent bond and the phosphamide unit is deployed in the organic framework. The presence of phosphamide in the repeating unit of the isolated amorphous POP material can be confirmed by 31P CPMAS NMR, FTIR, and Raman studies. The core-level N 2p and P 2p X-ray photoelectron spectra are in accordance with the presence of tertiary amine nitrogen attached to carbon and secondary amine nitrogen attached to phosphorus. Elemental analyses have depicted approximately 19.7% of phosphorus content in the material, which is being utilized to study the catalytic Appel reaction with 76% conversion of alcohol to a corresponding halide and TON of 462. Quasi in situ Raman study has identified that amino phosphine formed via in situ reduction of the phosphamide unit of the POP catalyzes the halogenation of primary and secondary alcohols with wide substrate scope and functional group tolerance. Kinetic studies have established a first-order dependence with respect to alcohol, while deuterium labeling experiments emphasize that the deprotonation of alcohol is the rate-limiting step. High thermal stability of the material, scope of easy catalyst recyclability, and a cumulative TON of 1386 have led the POP as an emerging pure organic material to be explored further for other phosphine-mediated organocatalysis.

Synthesis, characterisation and structural elucidation of novel 4-tert-butylbenzohydrazone and its Cu(II), Ni(II), Co(II) and Mn(II) complexes

ABSTRACT. 4-Tert-butylbenzohydrazone ligand was synthesised by reacting 4-tert-butylbenzohydrazide with dehydroacetic acid. Afterward, the Cu(II), Ni(II), Co(II), and Mn(II) complexes of 4-tert-butylbenzohydrazone were synthesised. All the synthesised compounds were characterised using elemental analysis, ESI-MS, IR, 1H-NMR and 13C-NMR spectroscopic methods. ESI-MS studies revealed ligand to metal stoichiometry of 1:1 for the Cu(II) complex, 2:1 for the Ni(II), Co(II), and Mn(II) complexes. IR studies showed that the ligand was coordinated to the metal ions through ONO donor atoms. The 1H NMR revealed that deprotonation did not occur in the ligand. Thus, the hydroxyl oxygen and the secondary amine nitrogen did not participate in the coordination. The proposed structures of the compounds conform with the analytical results.
 KEY WORDS: 4-Tert-butylbenzohydrazone, Metal complexes, Structure, Elucidation
 Bull. Chem. Soc. Ethiop. 2023, 37(6), 1411-1422. DOI: https://dx.doi.org/10.4314/bcse.v37i6.9

Synthesis, characterization, DFT and biological studies of Fe(II), Cu(II), and Zn(II) complexes of keto-imine chelators

Three naphthoquinone-based chelators, 2-(pyrimidin-2-ylamino)-2,3-dihydronaphthalene-1,4-dione (HLa) 2-((4,6-dihydroxypyrimidin-2-yl)amino-2,3-dihydronaphthalene-1,4-dione (HLb), and 2-((4,6-dimethylpyrimidin-2-yl)amino-2,3-dihydronaphthalene-1,4-dione (HLc), have been synthesized by the reaction of 2-hydroxy-1,4-napthoquinone with 2-aminopyrimidine, 2-amino-4,6-dihydroxypyrimidine, and 2-amino-4,6-dimethypyrimidine respectively. Reaction of the chelators with Fe2+; Cu2+ and Zn2+ sulphate; and acetate salts; plus 2,2′-bipyridine(B) gave the resultant heteroleptic M2+ complexes, which were characterized by analytical, 1H-and 13C NMR, FT-IR, UV–vis, ESI-MS, and TG-DSC analyses. The FT-IR and NMR results showed that the chelators are bidentate and chelated with the M2+ ions via their ketonic oxygen (>CO) and secondary amine nitrogen (HN) atoms. The μeff data and UV–vis spectral evaluations of the complexes provided credence to the 6-coordinate octahedral geometries of the complexes. DFT calculations were performed to understand the mode of complex formation as well as their geometry around the metal centers. Compared to the chelators, the heteroleptic complexes have improved antimicrobial actions attributed to the extra 2-nitrogenous atoms in the 2,2′-bipyridine moiety and the presence of active metal ions. The CuLc complexes displayed the best antibacterial performance with inhibitory effects of 34.0 mm. However, the ZnLb complexes recorded the best antifungal activity (33.0 mm), due to the absorption of Zn2+ ions on the surface of the fungiform cell walls. The antioxidant assays with ferrous ions show that all the keto-imine chelators showed good chelating abilities. HLc showed values of 78.76 plus 74.5 % separately at concentrations of 200 and 100 mg/mL, which are higher than that of the standard ascorbic acid. The DPPH radical scavenging activities of the heteroleptic complexes indicate that they can be used for the synthesis of drugs for the treatment of pathological diseases arising from oxidative stress.

Engineering strong electronegative nitrogen-rich porous organic polymer for practical durable lithium-sulfur battery

The practical application of porous organic polymers (POPs) in Li–S batteries (LiSBs) is severely hampered by low sulfur loading and weak chemisorption. Here, a novel organosulfur copolymer host (POP@F/S) with polar nitrogen-rich heteroatoms is prepared by in situ anchoring of sulfur in 3D perfluorinated hierarchical porous polymers via nucleophilic aromatic substitution reaction (SNAr) reaction. The design of hierarchical pore structure with high porosity not only offers strong physical confinement to polysulfide species but also increase the sulfur loading and buffer the volume change during lithiation. Notably, calculations and experimental results indicate that the triazine and secondary amine nitrogen atoms containing lone electron pairs can act as Lewis base sites to strongly interact with the terminal lithium ions in lithium polysulfide, thereby suppressing the shuttle effect. Attributed to these merits, LiSBs with POP@F/S composite cathode exhibit excellent rate capability and ultra-low capacity decay of only 0.019% per cycle after 500 cycles at 1C. Even more excitingly, a desirable areal capacity of 8.65 mAh cm−2 is delivered when with 7.9 mg cm−2 sulfur loading, and a satisfactory lifetime of over 150 cycles is maintained even under lean electrolyte (E/S = 5 μL mg−1), demonstrating remarkable potential in developing high-performance LiSBs.

Selective N-allylation via SN2ꞌ reaction: Synthesis, characterization, crystal structure, theoretical and biological studies of Ethyl (E)-2-(4-aminobenzene-1-sulphonylimino-thiazol-3-yl-methyl)-3-phenyl acrylate

The title compound ethyl (E)-2-(4-aminobenzene-1-sulphonylimino-thiazol-3-yl-methyl)-3-phenyl acrylate (BH-STZ) was synthesized by an SN2ꞌ reaction between 1:1 ratio of Ethyl 2-(acetoxy phenyl-methyl) acrylate (BH) and 4-amino-N-(1,3-thiazol-2-yl) benzenesulphonamide (STZ). It was characterized by FT-IR, 1H NMR, 13C NMR, DEPT 135, Mass, elemental analysis, and SCXRD. This study investigates the selective allylation of STZ at the secondary amine nitrogen over the primary amine nitrogen. It has been confirmed by the crystal structure of BH-STZ. In the BH-STZ, the hydrogen bonding interaction between primary amine and sulphonyl oxygen (NH.O) forms the β dimer. The photophysical properties (UV absorption and fluorescence emission) of BH-STZ have been studied. The theoretical FT-IR, UV, and SCXRD calculations based on density functional theory correlated well with the experimental results. The HOMO–LUMO energy gap indicated that BH-STZ has good chemical stability and lower hardness. The in vitro antibacterial activity of BH-STZ against a panel of pathogenic bacteria was assayed by the disc diffusion method. These results were compared with molecular docking studies between BH-STZ and the respective target protein from the bacteria. The compound was shown to be non-toxic to normal cells by both in vitro (using bacterial pathogen) and in vivo (using zebrafish) studies.

A turn-on fluorescence sensor based on Cu2+ modulated DNA-templated silver nanoclusters for glyphosate detection and mechanism investigation

The abuse application of glyphosate can result in a potential hazard for environment and human, however its ultrasensitive detection remains challenging. Herein, a Cu2+ modulated DNA-templated silver nanoclusters (DNA-AgNCs) sensor was constructed to sensitively determine glyphosate based on the turn-on fluorescence strategy. The fluorescence quenching of DNA-AgNCs occurred with the existence of Cu2+. Upon the presence of glyphosate, the functional groups on the surface of glyphosate could chelate with Cu2+, following the fluorescence recovery of DNA-AgNCs. Through the stoichiometric methods, we unveil that Cu2+-trigged fluorescence quenching mode is a combination of static and dynamic quenching with the static mode being predominant. In DNA-AgNCs/Cu2+ system, the carboxylate, amine, and phosphonate groups of glyphosate interact with Cu2+ through chelation, in which the carboxylate oxygen, the phosphonate oxygen atoms, and the monoprotonated secondary amine nitrogen atom and Cu2+ form chelate rings. This fluorescence sensor showed a desired linearity of glyphosate analysis under the optimum conditions, ranging from 15 to 100 μg/L with a low detection down to 5 μg/L. Moreover, the proposed sensor was successfully utilized to measure glyphosate in real samples, indicating a promising application in pesticide residues detection.

Facile Detection of Blood Creatinine Using Binary Copper-Iron Oxide and rGO-Based Nanocomposite on 3D Printed Ag-Electrode under POC Settings.

Metal nanoparticles have been helpful in creatinine sensing technology under point-of-care (POC) settings because of their excellent electrocatalyst properties. However, the behavior of monometallic nanoparticles as electrochemical creatinine sensors showed limitations concerning the current density in the mA/cm2 range and wide detection window, which are essential parameters for the development of a sensor for POC applications. Herein, we report a new sensor, a reduced graphene oxide stabilized binary copper-iron oxide-based nanocomposite on a 3D printed Ag-electrode (Fe-Cu-rGO@Ag) for detecting a wide range of blood creatinine (0.01 to 1000 μM; detection limit 10 nM) in an electrochemical chip with a current density ranging between 0.185 and 1.371 mA/cm2 and sensitivity limit of 1.1 μA μM-1 cm-2 at physiological pH. Interference studies confirmed that the sensor exhibited no interference from analytes like uric acid, urea, dopamine, and glutathione. The sensor response was also evaluated to detect creatinine in human blood samples with high accuracy in less than a minute. The sensing mechanism suggested that the synergistic effects of Cu and iron oxide nanoparticles played an essential role in the efficient sensing where Fe atoms act as active sites for creatinine oxidation through the secondary amine nitrogen, and Cu nanoparticles acted as an excellent electron-transfer mediator through rGO. The rapid sensor fabrication procedure, mA/cm2 peak current density, a wide range of detection limits, low contact resistance including high selectivity, excellent linear response (R2 = 0.991), and reusability ensured the application of advanced electrochemical sensor toward the POC creatinine detection.

Enrichment of Semiconducting Single-Walled Carbon Nanotubes with Indigo-Fluorene-Based Copolymers and Their Use in Printed Thin-Film Transistors and Carbon Dioxide Gas Sensors.

High-purity semiconducting single-walled carbon nanotubes (sc-SWCNTs) are promising for portable and high-sensitivity gas sensors because of their excellent physical and electrical properties. Here, we describe the synthesis of a novel indigo-fluorene-based copolymer (PFIDBoc) that has been designed to selectively enrich sc-SWCNTs with excellent purity (>99.9%) yet contain a latent function in the form of a tert-butoxy (t-BOC)-protected amine that can be later revealed and exploited for carbon dioxide (CO2) gas sensing. SWCNTs wrapped with the PFIDBoc polymer can be easily converted via an on-chip thermal process to reveal a vinylogous amide moiety with a secondary amine nitrogen within the indigo building block of the copolymer which is perfectly suited for CO2 recognition. Thin-film transistors and sensors were inkjet-printed onto rigid and flexible substrates, demonstrating the versatility of enriched PFIDBoc-derived sc-SWCNT dispersions. The printed transistors exhibited a mobility up to 9 cm2 V-1 s-1 and on/off current ratios >105. We further demonstrate herein a CO2 sensor for indoor air quality monitoring even in low humidity environments, possessing a linear response with up to ∼5.4% sensitivity and a dynamic range between 400 and 2000 ppm in air with a relative humidity of ∼ 40%.

Experimental and Theoretical Studies of the Environmental Sensitivity of the Absorption Spectra and Photochemistry of Nitenpyram and Analogs

Neonicotinoid (NN) pesticides have widespread use, largely replacing other pesticides such as the carbamates. Hence, there is a need to understand their environmental fates at a molecular level in various media, especially water. We report here the studies of a nitroenamine NN, nitenpyram (NPM), in aqueous solution where the absorption cross sections in the actinic region above 290 nm are observed to dramatically decrease compared to those in nonaqueous solvents. Quantum chemical calculations show that addition of a proton to the tertiary amine nitrogen in NPM breaks the conjugation in the chromophore, shifting the absorption to shorter wavelengths, consistent with experiment. However, surprisingly, adding a proton to the secondary amine nitrogen leads to its immediate transfer to the NO2 group, preserving the conjugation. This explains why the UV absorption of ranitidine (RAN), which has a similar chromophore but only secondary amine nitrogens, does not show a similar large blue shift in water. Photolysi...

Removal of Cr(III) from aqueous solution by silica-gel/PAMAM dendrimer hybrid materials.

Water pollution caused by Cr(III) is a serious environmental problem which bring adverse effect to environmental protection and public safety. Efficient removal of Cr(III) from aqueous solution is important for the remediation of Cr(III) pollution. Herein, a series of silica-gel/polyamidoamine (PAMAM) dendrimer hybrid materials (SG-G0~SG-G4.0) were used for the removal of Cr(III) from aqueous solution. The factors that affect the adsorption were extensively studied and the adsorption mechanism was demonstrated based on the experimental results and density functional theory (DFT) calculation. Result demonstrates the adsorption capacity of ester-terminated silica-gel/PAMAM dendrimers follow the order of SG-G2.5 > SG-G3.5 > SG-G1.5 > SG-G0.5, while that of amino-terminated ones decrease in the order of SG-G2.0 > SG-G4.0 > SG-G3.0 > SG-G1.0 > SG-G0. The highest adsorption is achieved at pH 4.0 for both ester- and amino-terminated materials. Adsorption kinetic indicates the adsorption equilibrium can be reached at about 240 and 180 min for amino- and ester-terminated hybrids, respectively. Adsorption kinetic can be well fitted by pseudo-second-order kinetic model with film diffusion process as the rate-limiting step. Adsorption isotherm follows Langmuir model with monolayer adsorption behavior. Fourier transform infrared spectra (FTIR) indicate the adsorption of Cr(III) by PAMAM dendrimer mainly involve the participation of N-H and C=O groups. DFT calculation demonstrates the uptake of Cr(III) by ester-terminated adsorbents mainly involves carbonyl oxygen and secondary amine nitrogen atoms to form tetra-coordinated chelate, while that of amino-terminated one tends to form hexa-coordinated chelates by carbonyl oxygen, primary and secondary amine nitrogen atoms.

Bioinorganic Chemistry of Iron

The X-ray crystallographic analysis of the single-crystal mugineic acid-Cu(II) complex showed that mugineic acid acts as a hexadentate ligand. Mugineic acid, a typical phytosiderophore, shows a marked stimulating effect on 59Fe-uptake and chlorophyll synthesis in rice plants. A salient feature is the higher reduction potential of the mugineic acid-Fe(III) complex than those of bacterial siderophores. X-ray diffraction study of the structurally analogous Co(III) complex of the mugineic acid-Fe(III) complex demonstrates that the azetidine nitrogen and secondary amine nitrogen, and both terminal carboxylate oxygens, coordinate as basal planar donors, and the hydroxyl oxygen and intermediate carboxylate oxygen bind as axial donors in a nearly octahedral configuration. The iron-transport mechanism in gramineous plants appears to involve the excretion of mugineic acid from the roots, which aids Fe(III)-solubilization and reduction of Fe(III) to Fe(II). Manganese peroxidase (MnP) is a component of the lignin degradation system of the basidiomycetous fungus, Phanerochaete chrysosporium. To elucidate the heme environment of this novel Mn(II)-dependent extracellular enzyme, we studied its ESR and resonance Raman spectroscopic properties. Consequently, it is most likely that the heme environment of MnP resembles that of cytochrome c peroxidase. In addition, degradation methods using basidiomycetous fungi or Fe3+-H2O2 mixed reagent were developed for dioxins and polychlorinated biphenyls. The complete amino acid sequences of respective [2Fe-2S] ferredoxins were determined and compared with those of other higher plants. Finally, the toxic effects of iron on human health and the development of novel antibacterial drugs capable of inhibiting the iron transport system of Vibrio vulnificus are described.

Modulation of Antimalarial Activity at a Putative Bisquinoline Receptor In Vivo Using Fluorinated Bisquinolines.

Antimalarials can interact with heme covalently, by π⋅⋅⋅π interactions or by hydrogen bonding. Consequently, the prototropy of 4-aminoquinolines and quinoline methanols was investigated by using quantum mechanics. Calculations showed mefloquine protonated preferentially at the piperidine and was impeded at the endocyclic nitrogen because of electronic rather than steric factors. In gas-phase calculations, 7-substituted mono- and bis-4-aminoquinolines were preferentially protonated at the endocyclic quinoline nitrogen. By contrast, compounds with a trifluoromethyl substituent on both the 2- and 8-positions, reversed the order of protonation, which now favored the exocyclic secondary amine nitrogen at the 4-position. Loss of antimalarial efficacy by CF3 groups simultaneously occupying the 2- and 8-positions was recovered if the CF3 group occupied the 7-position. Hence, trifluoromethyl groups buttressing the quinolinyl nitrogen shifted binding of antimalarials to hematin, enabling switching from endocyclic to the exocyclic N. Both theoretical calculations (DFT calculations: B3LYP/BS1) and crystal structure of (±)-trans-N1 ,N2 -bis-(2,8-ditrifluoromethylquinolin-4-yl)cyclohexane-1,2-diamine were used to reveal the preferred mode(s) of interaction with hematin. The order of antimalarial activity in vivo followed the capacity for a redox change of the iron(III) state, which has important implications for the future rational design of 4-aminoquinoline antimalarials.

Removal of Co(II) from fuel ethanol by silica-gel supported PAMAM dendrimers: Combined experimental and theoretical study

Silica-gel supported PAMAM dendrimers (SiO2-G0.5∼SiO2-G3.0) were used for the removal of Co(II) from fuel ethanol by batch method. The adsorption mechanism was revealed by combining the results of experiment and density functional theory (DFT) calculation. Results indicated the adsorption capacity was closely related with the generation number of PAMAM dendrimer, contact time, Co(II) concentration, and temperature. Amino-terminated PAMAM dendrimers exhibited better adsorption performance than the corresponding ester-terminated ones. Kinetic adsorption followed pseudo-second-order model and dominated by film diffusion. Isotherm adsorption can be well depicted by Langmuir isotherm model and proceeded by chemical mechanism. Thermodynamic parameters implied the adsorption was spontaneous, endothermic, and randomness incremental process. DFT calculation demonstrated that ester-terminated PAMAM tended to chelate with Co(II) by secondary amine nitrogen atoms and carbonyl oxygen atoms in a quadri-coordinated manner, while amino-terminated PAMAM preferred to act as tetradentate and pentadentate ligand to bind Co(II) with secondary amine nitrogen atom, carbonyl oxygen atom, and primary amine nitrogen atom. Charge transfer of the adsorption process mainly occurred from PAMAM dendrimer to Co(II).

Copper(II) complex as a precursor for formation of cyano-bridged pentanuclear FeIII-CuII bimetallic assembly: Synthesis, characterization, crystal structure and antibacterial activity

[CuL(ClO4)2] (1) (L = 3,10-diisobutyl-1,3,5,8,10,12-hexaazacyclotetradecane) was synthesized by condensation reaction of ethylenediamine, formaldehyde and iso-butylamine in absolute ethanol. Characterization of 1 utilized various spectroscopic techniques, viz. elemental analysis, electrospray ionization-mass spectrometry (ESI-MS), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis), diffuse reflectance spectroscopy (DRS) and thermogravimetric analysis (TGA). Based on these techniques, the structure of 1 was proposed as Cu(II) ion occupying octahedral geometry with four secondary amine nitrogens of the hexaazamacrocyclic ligand and two perchlorato anions. 1 was used as a precursor in the preparation of cyano-bridged bimetallic compound, [CuL]3[Fe(CN)6]2⋅5H2O (2), by reaction with K3[Fe(CN)6] in aqueous solution. Single-crystal X-ray analysis indicated that 2 crystallized in the monoclinic system with space group P21/n. The structure of 2 consisted of cyano-bridged FeIII-Cu II pentanuclear molecules having two [Fe(CN)6] 3− anions connected to three cis-[CuL] 2+ cations via two cis-cyanide ligands from each ferrate unit. In each of pentanuclear unit, the central [CuL] 2+ cation exhibited a distorted octahedral geometry while the other two units exhibited a distorted square pyramidal geometry. The room temperature magnetic moments of both complexes were measured to be 1.92 B.M. for 1 and 5.61 B.M. for 2. The in vitro antibacterial activity of 1 against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 strains were studied and compared with standard drugs, which showed moderate antibacterial activity compared with Penicillin and Gentamicin. A copper mononuclear complex was synthesized, characterized with various techniques, and used as a precursor to synthesize a pentanuclear (FeIII-CuII) complex. The Xray structure of the new pentanuclear complex is reported. The precursor copper complex exhibited moderate antibacterial activity.

Acid-Base Interactions of Polystyrene Sulfonic Acid in Amorphous Solid Dispersions Using a Combined UV/FTIR/XPS/ssNMR Study.

This study investigates the potential drug-excipient interactions of polystyrene sulfonic acid (PSSA) and two weakly basic anticancer drugs, lapatinib (LB) and gefitinib (GB), in amorphous solid dispersions. Based on the strong acidity of the sulfonic acid functional group, PSSA was hypothesized to exhibit specific intermolecular acid-base interactions with both model basic drugs. Ultraviolet (UV) spectroscopy identified red shifts, which correlated well with the color change observed in lapatinib-PSSA solutions. Fourier transform infrared (FTIR) spectra suggest the protonation of the quinazoline nitrogen atom in both model compounds, which agrees well with data from the crystalline ditosylate salt of lapatinib. X-ray photoelectron spectroscopy (XPS) detected increases in binding energy of the basic nitrogen atoms in both lapatinib and gefitinib, strongly indicating protonation of these nitrogen atoms. (15)N solid-state NMR spectroscopy provided direct spectroscopic evidence for protonation of the quinazoline nitrogen atoms in both LB and GB, as well as the secondary amine nitrogen atom in LB and the tertiary amine nitrogen atom in GB. The observed chemical shifts in the LB-PSSA (15)N spectrum also agree very well with the lapatinib ditosylate salt where proton transfer is known. Additionally, the dissolution and physical stability behaviors of both amorphous solid dispersions were examined. PSSA was found to significantly improve the dissolution of LB and GB and effectively inhibit the crystallization of LB and GB under accelerated storage conditions due to the beneficial strong intermolecular acid-base interaction between the sulfonic acid groups and basic nitrogen centers.

Mass Spectral and Chromatographic Studies on Some Halogenatedphenyl-2-Piperazinopropanones.

Gas chromatography-mass spectrometry (GC-MS) studies on the halogenatedphenyl-2-piperazinopropanones (XPPPOs): Twelve XPPPOs were subdivided into four groups of compounds and studied using GC-MS. The four studied groups include the three ring-substituted fluorophenylpiperazinopropanones, chlorophenylpiperazinopropanones, bromophenylpiperazinopropanones and trifluoromethylphenylpiperazinopropanones. The three compounds in each group have equal mass and many common mass spectral fragment ions. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions but acylation did not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. The perfluoroacyl derivatives of these piperazines were resolved on a stationary phase of 100% trifluoropropyl methyl polysiloxane (Rtx-200).

Coordination chemistry of a mono-dibenzofuran derivative of 1,4,7,10-tetraazacyclododecane

Copper(II) and cadmium(II) complex of a mono-dibenzofuran derivative of 1,4,7,10-tetraazacyclododecane (cyclen), L1, have been prepared by reaction of the mono-dibenzofuran-substituted cyclen with either copper(II) or cadmium(II) perchlorate in acetonitrile. This yielded the corresponding divalent metal complexes, [Cu(L1)](ClO4)2·H2O (C1) and [Cd(L1)](ClO4)2·H2O (C2), which were isolated as single crystals suitable for X-ray crystallography by diffusing diethyl ether into an acetonitrile solution of each complex. For the copper(II) complex, C1, the X-ray crystal structure revealed a distorted square pyramidal Cu(II) coordination sphere occupied by four amine nitrogens from the cyclen ring and one oxygen from the amide linkage present in L1. On the other hand, the metal center in the cadmium complex is seven coordinate, with two weakly bound acetonitrile molecules occupying two additional coordination sites about the Cd(II) center; these bind cis to the amide oxygen. The coordination geometry is best described as monocapped trigonal prismatic. In both complexes, the secondary amine nitrogens on the cyclen macrocycle form hydrogen bonds with perchlorate counterions present in the crystal lattice. Titration of L1 with various metal ions (Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+) in acetonitrile revealed a gradual quenching of the benzofuran emission with increasing [M2+] consistent with formation of metal complexes with a 1 : 1 M2+ : L1 stoichiometry. From the emission data, the conditional stability constant was determined to be 10–20 times higher for the Cu(II) complex than the other divalent metal complexes investigated.

Computational approach to understanding the mechanism of action of isoniazid, an anti-TB drug

Tuberculosis (TB) is an ancient disease caused by Mycobacterium tuberculosis (MTB), which remains a major cause for morbidity and mortality in several developing countries. Most drug-resistant MTB clinical strains are resistant to isoniazid (INH), a first-line anti-TB drug. Mutation in KatG, a catalase-peroxidase, of MTB is reported to be a major cause of INH resistance. Normally upon activation by KatG, INH is converted to an active intermediate which has antimycobacterial action in MTB. This INH intermediate in the presence of NADH forms INH-NAD adduct which inhibits inhA (2-trans-enoyl-acyl carrier protein reductase) of MTB, thus blocking the synthesis of mycolic acid, a major lipid of the mycobacterial cell wall. In this docking study, the high binding affinity of INH-NAD adduct towards InhA was observed in comparison with INH alone. In this study, two resistant mutants of KatG (S315T and S315N) were modeled using Modeller9v10 and docking analysis with INH was performed using AutoDock4.2 and the docking results of these mutants were compared with the wild type KatG. Docking results revealed the formation of a single hydrogen (H) bond between the secondary amine nitrogen (–NH) of INH with Thr or Asn residues in place of Serine at 315 position of KatG mutant strains respectively, whereas in the case of the wild type, there was no H-bond formation observed between INH and Ser315. The H-bond formation may prevent free radical formation by KatG in mutant strains thus the development of resistance to the drug. This in silico evidence may implicate the basis of INH resistance in KatG mutant strains.

An asymmetrical dinuclear copper(II) β-amino-oxime/oximato-diamine compound with Cu–(OH)–Cu and Cu–(N–O)–Cu bridging; [Cu2(detenoxH)(detenox)(OH)](ClO4)2 (detenoxH = 4,4-dimethyl-7-(N,N-diethylamine)-5-azaheptan-2-one oxime)

The dark blue compound [Cu2(detenoxH)(detenox)(OH)](ClO4)2 (detenoxH=4,4-dimethyl-7-(N,N-diethylamine)-5-azaheptan-2-one oxime), [Cu2(C12H27N3O)(C12H26N3O)(OH)](ClO4)2, is formed by reaction of (N,N-diethyl-ethane-1,2-diamine)copper(II) perchlorate, 4-methylpent-3-ene-2-one oxime and base. The asymmetrical dinuclear cation has ion Cu1 in asymmetrical square pyramidal coordination by the oxime nitrogen atom (Cu1–Noxime=2.041(3)Å) and the secondary amine nitrogen atom (Cu1–Nsecondary=1.995(3) Å) of a detenoxH ligand, the bridging oximato oxygen atom of the detenox− ligand bonded to Cu2 (Cu1–Ooximato=1.928(2)Å) and the bridging OH− ion (Cu1–OOH=1.928(3)Å) with rms displacements from the N2O2 plane±0.246(1) with Cu1 in the plane). The tertiary amine nitrogen atom of the detenoxH ligand is weakly coordinated axially (Cu1–Ntertiary=2.328(3)Å). Ion Cu2 is in tetrahedrally twisted square-planar coordination by a detenox− ligand, with Cu2–Noxime=1.992(3), Cu2–Nsecondary=1.979(3), Cu2–Ntertiary=2.053(3), and by the bridging hydroxide ion (Cu2–O=1.878(3)Å), with rms displacements from the N3O best plane ±0.178(2)Å, with Cu2 in the plane). The dinuclear cation has Cu1–O=N–Cu2 bridging by the oximato group of detenox− and Cu1–(OH)–Cu2 bridging by a hydroxide ion, with Cu⋯Cu=3.3136(6)Å. The components of the dinuclear cation are further linked by a hydrogen bond between the oxime OH and oximato O− groups. The effective magnetic moment of 2.21 B.M. indicates that there is no significant spin coupling.