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Alkyl Spacer (alkyl + spacer)
Selected AbstractsHantzsch 1,4-dihydropyridines containing a nitrooxyalkyl ester moiety to study calcium channel antagonist structure,activity relationships and nitric oxide releaseDRUG DEVELOPMENT RESEARCH, Issue 4 2000Jeffrey-Tri Nguyen Abstract A group of 3-nitrooxyalkyl 5-alkyl 1,4-dihydro-2,6-dimethyl-4-(pyridyl)-3,5-pyridinedicarboxylates were prepared using a modified Hantzsch reaction that involved the condensation of a nitrooxyalkyl acetoacetate with an alkyl 3-aminocrotonate and a pyridinecarboxaldehyde. 1H NMR nuclear Overhauser enhancement (nOe) studies for 3-(3-nitrooxypropyl) 5-isopropyl 1,4-dihydro-2,6-dimethyl-4-(2-pyridyl)-3,5-pyridinedicarboxylate (17) indicates a predominant rotamer exists in solution where the pyridyl nitrogen atom is orientated above the 1,4-DHP ring system, and the pyridyl nitrogen atom is antiperiplanar to the 1,4-DHP ring H-4 proton. Variable temperature 1H NMR studies (,30 to +60°C) showed the 1,4-DHP NH proton in 17 is H-bonded in CHCl3 solution. This interaction is believed to be due to intermolecular H-bonding between the pyridyl nitrogen free electron pair and the 1,4-DHP NH proton. In vitro calcium channel antagonist (CCA) activities were determined using a muscarinic-receptor-mediated Ca+2 -dependent contraction of guinea pig ileal longitudinal smooth muscle assay. This class of compounds exhibited lower CCA activity (IC50 = 5.3 × 10,6 to 3.5 × 10,8 M range) than the reference drug nifedipine (IC50 = 1.4 × 10,8 M). For compounds having C-3 ,CH2CH2ONO2 and C-4 pyridyl substituents, the C-5 alkyl was a determinant of CCA (i -Pr > the approximately equipotent i -Bu, t -Bu, and Et analogs). The point of attachment of the isomeric C-4 pyridyl substituent was a determinant of CCA when C-3 ,CH2CH2ONO2 and C-5 i -Pr substituents were present providing the potency profile 2-pyridyl , 3-pyridyl > 4-pyridyl. CCA with respect to the C-3 nitrooxyalkyl substituent was inversely dependent on the length of the alkyl spacer. The percent nitric oxide (·NO) released in vitro by this group of compounds (range of 0.03,0.43%/ONO2 group), quantified as nitrite by reaction with the Griess reagent, was lower than that for the reference drug glycerol trinitrate (3.81%/ONO2 group). Nitric oxide release studies showed that the %·NO released was dependent on the number of ONO2 groups/molecule. A QSAR study for this group of compounds showed a correlation between the specific polarizability descriptor (SpPol) and %·NO release. Drug Dev. Res. 51:233,243, 2000. © 2001 Wiley-Liss, Inc. [source] Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimicsFEBS JOURNAL, Issue 9 2000Kaoru Kuwabara Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and ,,,-unsaturated ,-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two ,-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a ,-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the ,,,-unsaturated ,-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules. [source] Effect of the Molecular Size of Analytes on Polydiacetylene ChromismADVANCED FUNCTIONAL MATERIALS, Issue 9 2010Donghwan Seo Abstract The pH chromism of polydiacetylenes (PDAs) is examined with respect to the molecular size and acidity of acid analytes, along with the alkyl spacer length of primary-amine-functionalized diacetylene (DA) lipids. pH turns out to be an important parameter to charge amine headgroups of PDA but a change in pH does not necessarily result in a PDA color change. The molecular size of acid analytes is identified as another factor that can produce a configurational change in PDA amine headgroups, followed by perturbation of the ene,yne conjugated backbone. In addition, the length of a flexible alkyl spacer between the amine headgroup and the amide group of the diacetylene lipids is found to strongly affect the degree of PDA chromatic transition. The longer alkyl spacer shows a smaller chromatic transition from blue to red phase. The alkyl spacer seems to provide a certain degree of freedom to the amine headgroup, thus decreasing the transfer of headgroup steric effects to the PDA backbone. These correlations found for PDA chromism are applied to the development of a system that colorimetrically detects diethyl phosphate (DEP), a degraded nerve agent simulant. PDA liposomes show a selective chromatic transition upon binding with DEP compared to other acid analytes. [source] Organotin catalysts grafted onto cross-linked polystyrene supports through polar spacersAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 2 2010Vanja Pinoie Abstract The present study investigates the suitability of a HypoGel support bearing oligomeric poly(ethylene glycol) (PEG) chains to act as an insoluble carrier for grafted organotin catalysts. Through the introduction of polar spacers, an improved swelling and site accessibility in the polar media typically involved in transesterification reactions are targeted. Advanced structural investigation shows that quantitative conversion into the targeted HypoGel-supported organotin trichloride is hampered by the existence of intra- and/or intermolecular donor-acceptor O,Sn interactions caused by the presence of donor moieties in the PEG-linker. Support is provided to the proposal that the latter interactions are at the origin of the moderate catalytic performance displayed by these HypoGel-supported catalysts, achieving only 41% conversion after 2 hours in the transesterification of ethyl acetate and n -octanol. In contrast with similar organotin catalysts supported by an alkyl spacer, the HypoGel-supported materials appear to be poorly recyclable and display poor leaching resistance. Copyright © 2009 John Wiley & Sons, Ltd. [source] Systematic Investigation of Photoinduced Electron Transfer Controlled by Internal Charge Transfer and Its Consequences for Selective PdCl2 CoordinationCHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2010Thomas Schwarze Abstract Fluoroionophores of fluorophore,spacer,receptor format were prepared for detection of PdCl2 by fluorescence enhancement. The fluorescent probes 1,13 consist of a fluorophore group, an alkyl spacer and a dithiomaleonitrile PdCl2 receptor. First, varying the length of the alkylene spacer (compounds 1,3) revealed a dominant through-space pathway for oxidative photoinduced electron transfer (PET) in CH2 -bridged dithiomaleonitrile fluoroionophores. Second, fluorescent probes 4,9 containing two anthracene or pyrene fragments connected through CH2 bridges to the dithiomaleonitrile unit were synthesized. Modulation of the oxidation potential (EOx) through electron-withdrawing or -donating groups on the anthracene moiety regulates the thermodynamic driving force for oxidative PET (,GPET) in bis(anthrylmethylthio)maleonitriles and therefore the fluorescence quantum yields (,f), too. The new concept was confirmed and transferred to pyrenyl ligands, and fluorescence enhancements (FE) greater than 3.2 in the presence of PdCl2 were achieved by 7 and 8 (FE=5.4 and 5.2). Finally, for comparison, monofluorophore ligands 10,13 were synthesized. [source] Donor-Bound Glycosylation for Various Glycosyl Acceptors: Bidirectional Solid-Phase Semisynthesis of Vancomycin and Its DerivativesCHEMISTRY - AN ASIAN JOURNAL, Issue 1 2007Takayuki Doi Prof. Abstract The glycosidation of a polymer-supported glycosyl donor, N -phenyltrifluoroacetimidate, with various glycosyl acceptors is reported. The application of the polymer-supported N -phenyltrifluoroacetimidate is demonstrated in the synthesis of vancomycin derivatives. 2- O -[2-(azidomethyl)benzoyl]glycosyl imidate was attached to a polymer support at the 6-position by a phenylsulfonate linked with a C13 alkyl spacer. Solid-phase glycosidation with a vancomycin aglycon, selective deprotection of the 2-(azidomethyl)benzoyl group, and glycosylation of the resulting 2-hydroxy group with a vancosamine unit were performed. Nucleophilic cleavage from the polymer support with acetate, chloride, azido, and thioacetate ions provided vancomycin derivatives in pure form after simple purification. The semisynthesis of vancomycin was achieved by deprotection of the acetate derivative. [source] Self-assembly of multinuclear complexes with enantiomerically pure chiral binaphthoxy imine ligands: Effect of the alkyl spacer connecting two binaphthyl units on the metal bindingCHIRALITY, Issue 9 2006Takeshi Maeda Abstract Metal complexing behavior of enantiomerically pure ,,,-diiminoalkanes possessing the two terminal binaphthyl units (L1 and L2) was studied. The ligands L1 and L2 were prepared by the reaction of optically pure 2,-butoxy-3-formyl-2-hydroxy-1,1,-binaphthyl with propane and pentane diamines. Reactions of L1 and L2 with equimolar amount of Cu(OAc)2 afforded quantitatively multinuclear complexes 1. The structure of 1 was confirmed by MALDI,TOF MS spectroscopy, X-ray single-crystal-structure analysis, and UV/vis and CD spectroscopic analyses. The reaction of L1 having a 1,3-propanediyl spacer resulted in the formation of a self-assembled product, which was assigned as enantiopure trinuclear circular helicate 1a, while the ligand having a 1,5-pentanediyl spacer L2 gave a different self-assembled product, dinuclear side-by-side complex 1b. The circular dichroism (CD) spectrum of 1a in solution showed intense Cotton effects in both the ,,,* transition of the naphthalene units and the LMCT region of the N,O -chelate moieties. The CD spectrum of 1b was completely different from that of 1a; in particular the Cotton effects in the LMCT region were very weak, contrary to those of 1a. These results suggest that 1a retains some chirality induced on the N,O -chelating moieties even in solution, while the induced chirality on the N,O -chelating moieties in 1b is not very significant, being consistent with the consequences of the X-ray single-crystal-structure studies. Chirality, 2006. © 2006 Wiley-Liss, Inc. [source] Toward an Allosteric Metallated ContainerEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 2 2009Helga Szelke Abstract Polytopic ligands L1 and L2 in which three 2,2,-bipyridine units are linked to a central tris(pyrid-2-yl)amine (L1) or tris(pyrid-2-yl)methanol (L2) moiety by alkyl spacers were prepared by multistep organic syntheses. The parent tris(pyrid-2-yl)-type ligands were shown to be modest-to-good chelators for Zn2+ and Cu2+ ions in solution, and bi- and tridentate N-coordination was confirmed by crystal structures of CuII and RuII complexes, respectively. FeII and RuII smoothly form stable, cage-like 1:1 complexes with L1 and L2, in which the metal ion is coordinated to the tris(bpy) site of the ligands. The vacant tris(pyrid-2-yl) site of these complexes is, however, a poor donor site for Zn2+ and Cu2+ ions. In addition, FeII modulates the coordination behaviour of the tris(pyrid-2-yl) site toward Zn2+: Whereas tris(5-methylpyrid-2-yl)amine forms a 2:1 complex with Zn2+ in CH2Cl2, [Fe(L1)]2+ forms a 1:1 Zn complex. Spectrophotometric titrations suggest that [Fe(L2)]2+ forms a polynuclear Zn2+ complex in CH2Cl2, possibly involving bridging coordination of the alcohol OH group, which contrasts the smooth formation of a 2:1 complex of the parent tris(pyrid-2-yl)-type ligand with Zn. FeII might therefore be considered as an allosteric effector, which modulates the metal binding properties of the second tris(pyrid-2-yl) site of L1 and L2. Contrary to expectation, Zn2+ and Cu2+ appear to associate weakly with donor atoms directed toward the exterior of the cage-like complexes [Fe(Ln)]2+ and [Ru(L1)]2+, rather than locating in the interior of the container by tripodal coordination to the tris(pyrid-2-yl) site.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Design syntheses and mitochondrial complex I inhibitory activity of novel acetogenin mimicsFEBS JOURNAL, Issue 9 2000Kaoru Kuwabara Some natural acetogenins are the most potent inhibitors of mitochondrial complex I. These compounds are characterized by two functional units [i.e. hydroxylated tetrahydrofuran (THF) and ,,,-unsaturated ,-lactone ring moieties] separated by a long alkyl spacer. To elucidate which structural factors of acetogenins, including their active conformation, are crucial for the potent inhibitory activity we synthesized a novel bis-acetogenin and its analogues possessing two ,-lactone rings connected to bis-THF rings by flexible alkyl spacers. The inhibitory potency of the bis-acetogenin with bovine heart mitochondrial complex I was identical to that of bullatacin, one of the most potent natural acetogenins. This result indicated that one molecule of the bis-acetogenin does not work as two reactive inhibitors, suggesting that a ,-lactone and the THF ring moieties act in a cooperative manner on the enzyme. In support of this, either of the two ring moieties synthesized individually showed no or very weak inhibitory effects. Moreover, combined use of the two ring moieties at various molar ratios exhibited no synergistic enhancement of the inhibitory potency. These observations indicate that both functional units work efficiently only when they are directly linked by a flexible alkyl spacer. Therefore, some specific conformation of the spacer must be important for optimal positioning of the two units in the enzyme. Furthermore, the ,,,-unsaturated ,-lactone, the 4-OH group in the spacer region, the long alkyl tail attached to the THF unit and the stereochemistry surrounding the hydroxylated bis-THF rings were not crucial for the activity, although these are the most common structural features of natural acetogenins. The present study provided useful guiding principles not only for simplification of complicated acetogenin structure, but also for further wide structural modifications of these molecules. [source] Synthesis and characterization of side-chain liquid crystalline polymers bearing cholesterol mesogenJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 10 2009Suk-Kyun Ahn Abstract A series of new norbornene carboxylic cholesteryl ester monomers with and without alkyl spacers, NBCh, and NBCh-n, respectively, were synthesized. New side-chain liquid crystalline homopolymers, PNBCh and PNBCh-n, were cleanly prepared using NBCh and NBCh-n, respectively, with Grubbs 2nd generation catalyst. Molecular and structural characterization of monomers and polymers were carried out by nuclear magnetic resonance, NMR, Fourier transform infrared, FT-IR, spectroscopy, and gel permeation chromatography, GPC. The thermal and liquid crystalline properties of the homopolymers were investigated by differential scanning calorimetry, DSC, thermogravimetric analysis, TGA, and polarized optical microscopy, POM. Small angle and wide angle X-ray studies of PNBCh-n in powder and fiber states not only confirmed the formation of smectic A mesophases, but also established their morphologies. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 2690,2701, 2009 [source] Studies on the modification of poly(,-bromoalkyl-1-glycidylether)s with 4,-methoxybiphenyl-4-oxy mesogenic groupsJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 23 2005J. M. Montornés Abstract A series of poly[,-(4,-methoxy-biphenyl-4-oxy)alkyl-1-glycidylether]s were synthesized by chemically modifying the corresponding poly(,-bromoalkyl-1-glycidylether)s with the sodium salt of 4-hydroxy-4,-methoxybiphenyl. New high-molecular-weight side-chain liquid-crystalline polymers were obtained with excellent yields and almost quantitative degrees of modification. They were all insoluble in THF and other common solvents. Characterization by 13C NMR confirmed that all the polymers had the expected structure. The liquid crystalline behavior of the polymers was analyzed by DSC and polarized optical microscopy, and mesophase assignments were confirmed by X-ray diffraction studies. Polymers that had alkyl spacers with n = 2 and 4 were smectic C, those that had spacers with n = 6 and 8 were nematic cybotactic, and those that had longer spacers (n = 10 and 12) were smectic C again. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5998,6006, 2005 [source] Spectroscopic and computational studies on self-assembly complexes of bis(pyrrol-2- ylmethyleneamine) ligands linked by alkyl spacers with Cu(II)JOURNAL OF RAMAN SPECTROSCOPY, Issue 5 2007Wei Li Abstract Bis(pyrrol-2-ylmethyleneamine) ligands and their mononuclear monomeric and dinuclear dimeric self-assembly complexes with Cu(II) were investigated by means of IR and Raman spectroscopies and density functional theory. The ground-state geometries were calculated by using the BeckeLeeYangParr composite exchange-correlation functional (B3LYP) and a combined basis set (LanL2DZ for Cu; 6,31G(d) for C, H, N), and they were compared with the single-crystal X-ray diffraction (XRD) structures. The DFT-calculated CuN bond lengths are generally higher by 0.001,0.040 Å than those determined through XRD. The vibrational spectra were also calculated at the same level of theory for the optimized geometries. The calculated wavenumbers were scaled by a uniform scaling factor and compared with the experimental fundamentals. The predicted spectra are in good agreement with the experimental ones with the deviations generally less than 30 cm,1. In comparison with the spectra of the ligands, the coordination effect shifts the ,(CN) wavenumber by about 50 cm,1 toward a lower value. Because of the weak intermolecular CH···Cu hydrogen bond, the CuN stretching mode is shifted toward a lower wavenumber. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||