Quinoline-Proline,Triazole Hybrids: Design,Synthesis, Antituberculosis,Molecular Docking,and ADMET Studies

A series of novel quinoline-proline hybrids ( 11a-g ) and quinoline-proline-1,2,3-triazole hybrids ( 12-14 ) were synthesized by click chemistry based on molecular hybridization concept and were characterized by NMR, mass spectrometry, and elemental analysis. All the titled target compounds were tested for antitubercular activity by MABA and LORA methods by in vitro. Interestingly, two compounds (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-nitrobenzamido)-N-phenylpyrrolidine-2-carboxamide ( 11b ) and (2R,4S)-1-((2-cyclopropyl-4-(4-fluorophenyl)-quinolin-3-yl)-methyl)-4-(4-fluorobenzamido)-N-phenylpyrrolidine-2-carboxamide ( 11c ) exhibited significant activity against the tested Mycobacterium tuberculosis H37Rv strain. Further, the cytotoxicity ( CC ₅₀ ) profile of the titled compounds against the Vero cell was performed and discussed. A molecular docking study of the hit compounds ( 11b and 11c ) was also performed to find their putative binding interaction with the active site of the target proteins. Finally, in silico ADMET properties were also predicted for all the synthesized molecules to evaluate their drug-likeness behavior.     

Rh(II) and Rh(I) two-legged piano-stool complexes: structure,reactivity, and electronic properties

The ligand 1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene, 3, was used to synthesize a mononuclear Rh(II) complex [(eta(1):eta(6):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh][PF(6)](2), 6+, in a two-legged piano-stool geometry. The structural and electronic properties of this novel complex including a single-crystal EPR analysis are reported. The complex can be cleanly interconverted with its Rh(I) form, allowing for a comparison of the structural properties and reactivity of both oxidation states. The Rh(I) form 6 reacts with CO, tert-butyl isocyanide, and acetonitrile to form a series of 15-membered mononuclear cyclophanes [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(3)][PF(6)] (8), [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CNC(CH(3))(3))(2)][PF(6)] (10), and [(eta(1):eta(1)-1,4-bis[4-(diphenylphosphino)butyl]-2,3,5,6-tetramethylbenzene)Rh(CO)(CH(3)CN)][PF(6)] (11). The Rh(II) complex 6+ reacts with the same small molecules, but over shorter periods of time, to form the same Rh(I) products. In addition, a model two-legged piano-stool complex [(eta(1):eta(6):eta(1)-1,4-bis[3-(diphenylphosphino)propoxy]-2,3,5,6-tetramethylbenzene)Rh][B(C(6)F(5))(4)], 5, has been synthesized and characterized for comparison purposes. The solid-state structures of complexes 5, 6, 6+, and 11 are reported. Structure data for 5: triclinic; P(-)1; a = 10.1587(7) A; b = 11.5228(8) A; c = 17.2381(12) A; alpha = 96.4379(13) degrees; beta = 91.1870(12) degrees; gamma = 106.1470(13) degrees; Z = 2. 6: triclinic; P(-)1; a = 11.1934(5) A; b = 12.4807(6) A; c = 16.1771(7) A; alpha = 81.935(7) degrees; beta = 89.943(1) degrees; gamma = 78.292(1) degrees; Z = 2. 6+: monoclinic; P2(1)/n; a = 11.9371(18) A; b = 32.401(5) A; c = 12.782(2) A; beta = 102.890(3) degrees; Z = 4. 11: triclinic; P(-)1; a = 13.5476(7) A; b = 13.8306(7) A; c = 14.9948(8) A; alpha = 74.551(1) degrees; beta = 73.895(1) degrees; gamma = 66.046(1) degrees; Z = 2.     

Novel synthesis, properties, and oxidizing ability of 11,13-disubstituted 3,8-methanocycloundeca[8,9-b]pyrimido[5,4-d]-furan-12(11H),14(13H)-dionylium tetrafluoroborates

Synthesis of novel 4,9-methanoundecafulvene [5-(4,9-methanocycloundeca-2',4',6',8',10'-pentaenylidene)pyrimidine-2(1H),4(3H),6(5H)-trione] derivatives 10a-c was accomplished. Their structural characteristics were investigated on the basis of the 1H and 13C NMR and UV-vis spectra. Upon treatment with DDQ, 10a-c underwent oxidative cyclization to give novel 11,13-disubstituted 3,8-methanocycloundeca[8,9-b]pyrimido[5,4-d]furan-12(11H),14(13H)-dionylium tetrafluoroborates 11a-c*BF4- in good yields. The spectroscopic properties of 11a-c*BF4- were studied, and the structural characterization of 11b*BF4- was performed by the X-ray crystal analysis. Cations 11a-c were very stable, and their pKR+ values were determined spectrophotometrically to be 8.3-8.9. The electrochemical reduction of 11a-c exhibited low reduction potentials at -0.43 to -0.45 (V vs Ag/AgNO3) upon cyclic voltammetry (CV). In a search for reactivity, reactions of 11a*BF4- with some nucleophiles, hydride and diethylamine, were carried out to clarify that the methano-bridge controls the nucleophilic attacks to occur with endo-selectivity. The photoinduced oxidation reactions of 11a*BF4- toward some amines under aerobic conditions were carried out to give the corresponding carbonyl compounds in more than 100% yield.     

Twisted imide bond in noncyclic imides. Synthesis and structural and vibrational properties of N,N-bis(furan-2-carbonyl)-4-chloroaniline

A novel imide compound (C(16)H(10)ClNO(4)) was synthesized in a single step by the reaction of 2-furoic acid with 4-chloroaniline in a 2:1 molar ratio using carbonyldiimidazole (CDI) in dry THF. The structure was supported by spectroscopic and elemental analyses and the single-crystal X-ray diffraction data. Crystallographic studies revealed that the compound crystallized in a monoclinic system with space group P2(1)/c and unit cell dimensions a = 12.2575(5) ?, b = 7.7596(2) ?, c = 15.0234(7) ?, α = γ = 90°, β = 92.771(4)°, V = 1427.25(10) ?(3), Z = 4. The imide bond is twisted, and the O═C-N-C(O) units deviate significantly from planarity with dihedral angles around the imide group reaching ca. -150.3° (C1-N1-C2-O21 = -148.8° and C2-N1-C1-O11 = -151.9°). The nonplanarity of the imide moiety and the related conformational properties are discussed in a combined approach that includes the analysis of the vibrational spectra together with theoretical calculation methods, especially in terms of natural bond orbital (NBO) calculations.     

Biomimetic synthesis of hyperolactones

Through a biomimetic pathway, hyperolactone D, 4-hydroxyhyperolactone D, and hyperolactone C were synthesized from methyl acetoacetate via Weiler's dianion method, asymmetric allylic alkylation, biomimetic lactonization, oxidation, and cyclization. The stereochemistry of the quaternary carbon was controlled efficiently by Palladium-catalyzed asymmetric allylic alkylation. This strategy was also used for the synthesis of hyperolactone B.     

Synthesis and structural characterization of novel silenes stabilized by intramolecular coordination of a dialkylamino group

Two intramolecularly donor-stabilized silenes, 1-(8-dimethylamino-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (6a) and 1-(2-dimethylaminomethylphenyl)-1,2,2-tris(trimethylsilyl)silene (6b), were synthesized according to a novel one-step process by the reaction of (dichloromethyl)tris(trimethylsilyl)silane (1) with a twofold molar excess of 8-dimethylamino-1-naphthyllithium or 2-(dimethylaminomethyl)phenyllithium, respectively. Compounds 6a and 6b are thermally stable compounds. X-ray structural analyses of both silenes revealed strong donor-acceptor interactions between the dialkylamino groups and the electrophilic silene silicon atoms (Si-N distances: 6a: 1.751(3) A; 6b: 1.749(3) A) that lead to pyramidalization at the silicon centers. In contrast, the configuration at the silene carbon atoms was found to be planar. The Si=C distances (6a: 1.751(3) A; 6b: 1.749(3) A) fit with literature data of comparable compounds. Addition of water or methanol to the Si=C bonds of 6a,b afforded the silanols 7a,b and the methoxysilanes 8a,b, respectively. The compound 1-(8-dimethylaminomethyl-1-naphthyl)-1,2,2-tris(trimethylsilyl)silene (6c), generated following the same procedure by the reaction of 1 with 8-(dimethylaminomethyl)-1-naphthyllithium (molar ratio 1:2) proved to be unstable at room temperature and underwent rapid insertion of the Si=C group into a methylene C-H bond of the dimethylaminomethylnaphthyl ligand to afford the 1-silaacenaphthene 9.     

Lipophilicity coefficients of potential tumor imaging agents, positron-labeled O(6)-benzylguanine derivatives

Novel radiolabeled O(6)-benzylguanine (O(6)-BG) derivatives, 6-O-[(11)C]-[(methoxymethyl)benzyl]guanines ([(11)C]p-O(6)-MMBG, 1a; [(11)C]m-O(6)-MMBG, 1b; [(11)C]o-O(6)-MMBG, 1c), 2-amino-6-O-[(11)C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([(11)C]p-O(6)-AMMP, 2a; [(11)C]m-O(6)-AMMP, 2b; [(11)C]o-O(6)-AMMP, 2c), 2-amino-6-O-[(11)C]-[(methoxymethyl)benzyloxy]-9-benzyl purines ([(11)C]p-O(6)-AMBP, 3a; [(11)C]m-O(6)-AMBP, 3b; [(11)C]o-O(6)-AMBP, 3c), 2-amino-6-O-benzyloxy-9-[(11)C]-[(methoxycarbonyl)methyl]purine ([(11)C]ABMMP, 4), and 2-amino-6-O-benzyloxy-9-[(11)C]-[(4'-methoxycarbonyl)benzyl]purine ([(11)C]ABMBP, 5), have been synthesized for evaluation as potential novel positron emission tomography tumor imaging agents. The ability of O(6)-BG analogs to penetrate the blood--brain barrier in brain tumor could be due, at least in part, to their lipophilicity. In this paper, we measured lipophilicity coefficients (log P) of compounds 1--5 by the C(18) HPLC method. These log P values were compared, and correlations between lipophilicity and biological activity of selected analogs were made. The results suggest the appropriate level of lipophilic character in this class of compounds as useful imaging agents appears to be in the range of 1.4--2.6.     

Synthesis and structural characterization of a new series of vanadoselenites, [Se(x)V(4-x)O(12-x)](4-x)- (x=1,2)

Two new vanadoselenites, [SeV(3)O(11)](3)(-) and [Se(2)V(2)O(10)](2)(-), were synthesized by reacting SeO(2) with VO(3)(-). Single-crystal X-ray structural analyses of [(n-C(4)H(9))(4)N](3)[SeV(3)O(11)].0.5H(2)O [orthorhombic, space group P2(1)2(1)2, a = 22.328(5) A, b = 44.099(9) A, c = 12.287(3) A, Z = 8] and [[(C(6)H(5))(3)P](2)N](2)[Se(2)V(2)O(10)] [monoclinic, space group P2(1)/n, a = 12.2931(3) A, b = 13.5101(3) A, c = 20.9793(5) A, beta = 106.307(1) degrees, Z = 2] revealed that both anions are composed of Se(x)()V(4)(-)(x)()O(4) rings. The (51)V, (77)Se, and (17)O NMR spectra established that both [SeV(3)O(11)](3)(-) and [Se(2)V(2)O(10)](2)(-) anions maintain this ring structure in solution.     

Synthesis, Structure and Photoluminescence of(CH3-4, 4'-H2bipy)-(HgCl4)with CH3-4, 4'-H2bipy Generated in Situ

A novel viologen(4,4'bipyridinium)-based complex(CH3-4,4'-H2bipy)(HgCl4)(1),in which the CH3-4,4'-H2bipy(MQ2+)was generated in situ,has been synthesized via hydrothermal reaction and structurally characterized.Complex 1 crystallizes in the space group P21/c of monoclinic system with four formula units in a cell:a = 8.1848(6),b = 21.809(2),c = 9.0285(6)(A),β =.107.377(1)°,V= 1538.0(2)(A)3,C11H11Cl4HgN2,Mr = 513.61,Dc = 2.218 g/cm3,S = 1.009,μ(MoKα)= 10.685 mm-1,F(000)= 956,R = 0.0360 and wR = 0.0812.The crystal structure analysis reveals that the title complex features an isolated structure based on a CH3-4,4'-H2bipy moiety and a mercury atom terminally bound by four chlorine atoms.Photoluminescence investigation reveals a strong emission in blue region,which may originate from π→π* charge-transfer interaction of the CH3-4,4'-H2bipy moiety.     

亚甲基蒽苯乙烯吡啶盐的合成、结构及双光子吸收性质

以氯化4-甲基-N-9-亚甲基蒽吡啶盐为原料,合成了一种新型的苯乙烯吡啶盐,通过红外、核磁共振氢谱、碳谱、电喷雾质谱、单晶X射线衍射等测试技术对化合物的结构进行了表征。单晶X射线衍射结果表明,该化合物属于单斜晶系,空间群为P21/c,晶胞参数a=1.255 7(1)nm,b=1.539(1)nm,c=2.220 2(8)nm,β=101.099(1)°,V=4.210 5(4)nm3,Z=4,Dc=1.159 g/cm3。用1 064 nm皮秒脉冲激光研究其三阶非线性光学特性,双光子吸收系数β=0.028 cm/GW,吸收截面为σ=8.68×10-48cm4.s.photon-1,表明目标化合物具有良好的三阶非线性光学性质。     

Synthesis and Crystal Structure of (E)-4-(Benzyloxy)-2-(cinnamoyloxy)-N,N,N-trimethyl-4-oxobutan-1-aminium Chloride as a Double-prodrug

A novel hydrochloride quaternary ammonium salt (E)-4-(benzyloxy)-2-(cinnamo- yloxy)-N,N,N-trimethyl-4-oxobutan-1-aminium chloride (C23H29NO4Cl2, Mr = 454.37) has been synthesized via the sequence of acetylation and esterification by using L-carnitine (L-4-N-trimethy- lammonium-3-hydroxybutyric acid, LC) and cinnamic acid as the starting materials, and its crystal structure was determined by single-crystal X-ray diffraction method. The crystal belongs to monoclinic, space group P212121 with a = 10.1670(4), b = 10.4488(4), c = 22.9795(11) ?, V = 2441.18(18) ?3, Z = 4, Dc = 1.236 g/cm3, μ(MoKα) = 0.293 mm?1, F(000) = 960, Flack factor = –0.01(11), the final R = 0.0489 and wR = 0.1550 for 3350 observed reflections (I > 2σ(I)) and R = 0.0953 for all 5648 unique reflections. The crystal structure involves a conjugated system which shows a reverse olefin structure.     

新型含卤噻唑类酰腙化合物的合成及其与小牛胸腺DNA的相互作用

以2-氨基噻唑-4-甲酸乙酯和水合肼为原料,制得2-氨基噻唑-4-甲酰肼(2); 2与卤代(F, Cl, Br)对苯甲醛反应,合成了3种新型的含卤噻唑类酰腙化合物［C₁₁H₉N₄OSF(3a), C₁₁H₉N₄OSCl(3b)和C₁₁H₉N₄OSBr(3c)］,其结构和性能经元素分析,XRD和TG-DTG表征。结果表明：3a和3c属于三斜晶系,Pī空间群;3b属于单斜晶系,P2(1)/c空间群。3a~3c的热稳定性均较好,最大热分解过程的表观活化能均大于100 kJ·mol^-1。采用UV-Vis研究了3a~3c与小牛胸腺DNA(CT-DNA)的相互作用。结果表明：3a~3c与CT-DNA均以插入方式相互作用。     

Molecular wires comprising pi-extended ethynyl- and butadiynyl-2,5-diphenyl-1,3,4-oxadiazole derivatives: synthesis, redox, structural, and optoelectronic properties

2,5-Diphenyl-1,3,4-oxadiazole (OXD) derivatives with terminal ethynyl- (4a,b) and butadiynyl- (8a,b) substituents have been synthesized in high yields. 2-Methyl-3,5-hexadiyn-2-ol has not been exploited previously in the synthesis of terminal butadiynes. Crystals of 8a and 8b are remarkably stable to long-term storage under ambient conditions. The X-ray crystal structure of 8a reveals that the butadiyne moieties are spatially isolated by the aromatic moieties, which explains the high stability. Two series of derived pi-conjugated molecules, Donor-(C[triple bond]C)(n)-OXD (n = 1, 2) and OXD-(C[triple bond]C)(n)-Donor-(C[triple bond]C)(n)-OXD (n = 1) [Donor = tetrathiafulvalene (TTF), bithiophene, 9-(4,5-dimethyl-1,3-dithiol-2-ylidene)fluorene, and triphenylamine], have been synthesized using Sonogashira reactions and characterized by X-ray crystallography, cyclic voltammetry, and optical absorption/emission spectroscopy. The electron-withdrawing effect of the OXD units is manifested by a positive shift of the donor oxidation waves in these systems: the butadiynylene spacer (n = 2) further shifts the first oxidation waves by 40-80 mV compared to analogues n = 1. The absorption spectra of TTF-OXD hybrids 10d and 11 are blue-shifted by 80 nm compared to the bithienyl-bridged derivative 10f and are similar to the butadiynyl-OXD building-block 8a, demonstrating that conjugation is disrupted by a neutral TTF unit. Solutions of the TTF-OXD and 9-(4,5-dimethyl-1,3-dithiol-2-ylidene)fluorene-OXD hybrids, 10d, 10g, 11, and 13, are only very weakly fluorescent due to quenching from the electron-donor moieties. In contrast, the triphenylamine-OXD hybrids 12a, 12b, 14a, and 14b are fluorescent; the PLQYs of the butadiynylene derivatives 14a and 14b are lower than those of the ethynylene-bridged analogues 12a and 12b.     

Synthesis, Crystal Structure and Binding Properties of 6H,7H,13H,14H-5a,6a,7a,12a,13a,14a- Hxaazbenz[f]indeno[2,1,8-ija]naphth[2,3- f]azulene-14b,14c-dicarboxylic-5,8,12,15- tetrahydro-6,8,14-trioxo-diethyl Ester

The title compound 6H,7H,13H,14H-5a,6a,7a,12a,13a,14a-hxaazbenz[f]indeno[2,1,8- ija]naphth[2,3-f]azulene- 14b, 14c-dicarboxylic-5,8,12,15-tetrahydro-6,8,14-trioxo-diethyl ester （C27H26N6OT, Mr = 546.54） has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P211c with a = 8.8129（6）, b = 17.9883（13）, c = 16.2623（11）A, β = 98.770（2）°, V = 2547.9（3）A3, Z = 4, De= 1.425 g/cm3, p（MoKa） = 0.105 mm-1, F（000） = 1144, the final R = 0.0672 and wR = 0.1162 for 2275 observed reflections with I 〉 2σ（I）. The crystal structural analysis shows that intermolecular C-H...O hydrogen bonds and π-π stacking interactions result in a three-dimensional framework. The binding study by fluorescence spectroscopy titration showed that he title compound can selectively recognize Fe3＋ with fluorescence quenching.     

Synthesis and Structure of a Novel Ion-pair Palladium(Ⅱ) Compound Containing 2-Thioxo-1,3-dithiole-4,5-bis(thiolate)

A novel ion-pair palladium(Ⅱ) compound,(NO2BzPy)2[Pd(dmit)2](NO2BzPy+ = 1-(4-nitrobenzyl)pyridinium,dmit2-= 2-thioxo-1,3-dithiole-4,5-bis(thiolate)),was synthesized and characterized by single-crystal X-ray structure determination.This compound crystallizes in the monoclinic system,space group P21/n with a = 10.4463(11),b = 8.5627(9),c = 20.017(2) ,β = 97.7730(10)°,V = 1774.1(3) 3,Z = 2,C30H22N4O4S10Pd,Mr = 929.52,Dc = 1.740 g/cm3,μ = 1.155 mm-1,S = 1.006,F(000) = 936,R = 0.0354 and wR = 0.0675.The most intriguing general structural feature of the compound is the completely segregated columnar stacks of anions and cations.There exist hydrogen-bonding interactions within the cation column.     

Synthesis and Crystal Structure of 1-（4-Chlorophenyl）-2-cyano-3-amino-3a-hydroxy-3a,3b ,6, 7-te trah y drobenzo[ 4,5]indene

1 INTRODUCTION dimerization of α,β-unsaturated ketones[10]. Herein we discuss the crystal structure of the title compound In the early seventies three groups of investiga- synthesized by the reaction of 2-cyano-3-(4-chloro- tors[1~3] have established that low-valent titanium phenyl)-3-(1-tetralon-2-yl) induced by TiCl4/Zn system. can abstract oxygen from ketones or aldehydes, lead- When 2-cyano-3-(4-chlorophenyl)-3-(1-tetra- lon-2-yl) ing to the formation of olefins. A variety of other…     

Sandwich-type phosphotungstates: structure,electrochemistry, and magnetism of the trinickel-substituted polyoxoanion [Ni(3)Na(H(2)O)(2)(PW(9)O(34))(2)](11-)

The novel nickel-substituted, dimeric phosphotungstate [Ni(3)Na(H(2)O)(2)(PW(9)O(34))(2)](11-) (1) has been synthesized and characterized by IR spectroscopy, elemental analysis, and electrochemistry. X-ray single-crystal analysis was carried out on Na(11)[Ni(3)Na(H(2)O)(2)(PW(9)O(34))(2)].21.25H(2)O, which crystallizes in the triclinic system, space group P1, with a = 12.2467(6) A, b = 16.6031(7) A, c = 22.4017(12) A, alpha = 73.9870(10) degrees, beta = 87.6060(10) degrees, gamma = 79.344(2) degrees, and Z = 2. The polyanion consists of two lacunary B-alpha-[PW(9)O(34)](9-) Keggin moieties linked via three nickel(II) centers and a sodium ion. The structure of 1 is composed of two fused Keggin fragments that represent different Baker-Figgis isomers (alpha- vs beta-type). Electrochemical studies show that 1 exhibits a stable and reproducible voltammetric pattern, with a first wave featuring a chemically reversible four-electron/four-proton process. An investigation of the magnetic properties indicates that the three nickel centers exhibit ferromagnetic exchange interaction.     

En route to the formation of high-efficiency, osmium(II)-based phosphorescent materials

Triosmium cluster complexes [Os3(CO)8(fppz)2] (2a) and [Os3(CO)8(fptz)2] (2b) bearing two 2-pyridyl azolate ligands were synthesized in an attempt to establish the reaction mechanism that gives rise to the blue-emitting phosphorescent complexes [Os(CO)2(fppz)2] (1a) and [Os(CO)2(fptz)2] (1b) [(fppz)H = 3-(trifluoromethyl)-5-(2-pyridyl)pyrazole; (fptz)H = 3-(trifluoromethyl)-5-(2-pyridyl)triazole]. X-ray structural analysis of 2b showed an open triangular metal framework incorporating multisite-coordinated 2-pyridyltriazolate ligands. Treatment of 2 with the respective 2-pyridylazolate ligand led to the formation of blue-emitting complex 1b, confirming their intermediacy, while the reaction of 2b with phosphine ligand PPh2Me afforded two hitherto novel hydride complexes 3 and 4, for which the reversible interconversion was clearly established at higher temperatures (> 180 degrees C). The single-crystal X-ray diffraction analyses of 3 and 4 confirmed their monometallic and isomeric nature, together with the coordination of two phosphine ligands located in the trans-disposition and one CO and one hydride located opposite to the pyridyl triazolate chelate. Subtle differences in photophysical properties were examined for isomers 3 and 4 on the basis of steady state absorption and emission, the relaxation dynamics, and temperature-dependent luminescent studies. The results, in combination with time-dependent density function theory (TDDFT) calculations, provide fundamental insights into the future design and preparation of highly efficient phosphorescent emitters.