RESUMO
The synthesis and characterization of the first supramolecular aggregates incorporating the organometallic cyclo-P3 ligand complexes [CpRMo(CO)2(eta3-P3)] (CpR=Cp (C5H5; 1a), Cp* (C5(CH3)5; 1b)) as linking units is described. The reaction of the Cp derivative 1a with AgX (X=CF3SO3, Al{OC(CF3)3}4) yields the one-dimensional (1D) coordination polymers [Ag{CpMo(CO)2(mu,eta3:eta1:eta1-P3)}2]n[Al{OC(CF3)3}4]n (2) and [Ag{CpMo(CO)2(mu,eta3:eta1:eta1-P3)}3]n[X]n (X=CF3SO3 (3a), Al{OC(CF3)3}4 (3b)). The solid-state structures of these polymers were revealed by X-ray crystallography and shown to comprise polycationic chains well-separated from the weakly coordinating anions. If AgCF3SO3 is used, polymer 3a is obtained regardless of reactant stoichiometry whereas in the case of Ag[Al{OC(CF3)3}4], reactant stoichiometry plays a decisive role in determining the structure and composition of the resulting product. Moreover, polymers 3a, b are the first examples of homoleptic silver complexes in which Ag(I) centers are found octahedrally coordinated to six phosphorus atoms. The Cp* derivative 1b reacts with Ag[Al{OC(CF3)3}4] to yield the 1D polymer [Ag{Cp*Mo(CO)2(mu,eta3:eta2:eta1-P3)}2]n[Al{OC(CF3)3}4]n (4), the crystal structure of which differs from that of polymer 2 in the coordination mode of the cyclo-P3 ligands: in 2, the Ag+ cations are bridged by the cyclo-P3 ligands in a eta1:eta1 (edge bridging) fashion whereas in 4, they are bridged exclusively in a eta2:eta1 mode (face bridging). Thus, one third of the phosphorus atoms in 2 are not coordinated to silver while in 4, all phosphorus atoms are engaged in coordination with silver. Comprehensive spectroscopic and analytical measurements revealed that the polymers 2, 3a, b, and 4 depolymerize extensively upon dissolution and display dynamic behavior in solution, as evidenced in particular by variable temperature 31P NMR spectroscopy. Solid-state 31P magic angle spinning (MAS) NMR measurements, performed on the polymers 2, 3b, and 4, demonstrated that the polymers 2 and 3b also display dynamic behavior in the solid state at room temperature. The X-ray crystallographic characterisation of 1b is also reported.
Assuntos
Polímeros/síntese química , Prata/química , Dióxido de Carbono/química , Cátions/química , Ciclização , Ligantes , Estrutura Molecular , Fósforo/química , Raios XRESUMO
N1-Aryl(heteroaryl)alkyl-N2-[3-(1H-imidazol-4-yl)propyl]guanidines are potent histamine H2-receptor (H2R) agonists, but their applicability is compromised by the lack of oral bioavailability and CNS penetration. To improve pharmacokinetics, we introduced carbonyl instead of methylene adjacent to the guanidine moiety, decreasing the basicity of the novel H2R agonists by 4-5 orders of magnitude. Some acylguanidines with one phenyl ring were even more potent than their diaryl analogues. As demonstrated by HPLC-MS, the acylguanidines (bioisosteres of the alkylguanidines) were absorbed from the gut of mice and detected in brain. In GTPase assays using recombinant receptors, acylguanidines were more potent at the guinea pig than at the human H2R. At the hH1R and hH3R, the compounds were weak to moderate antagonists or partial agonists. Moreover, potent partial hH4R agonists were identified. Receptor subtype selectivity depends on the imidazolylpropylguanidine moiety (privileged structure), opening an avenue to distinct pharmacological tools including potent H4R agonists.
Assuntos
Guanidinas/síntese química , Guanidinas/farmacologia , Agonistas dos Receptores Histamínicos/química , Agonistas dos Receptores Histamínicos/farmacologia , Imidazóis/síntese química , Imidazóis/farmacologia , Receptores Histamínicos H2/metabolismo , Acilação , Animais , Linhagem Celular , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Guanidinas/química , Cobaias , Agonistas dos Receptores Histamínicos/síntese química , Humanos , Imidazóis/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade , Fatores de TempoRESUMO
[structure: see text] Methoxypyrrole amino acids (MOPAS) have been prepared and were introduced into small peptides with hairpin structures. The intra- and intermolecular binding properties of this heterocyclic amino acid mimicking a dipeptido beta-strand was investigated by NMR titration and X-ray crystal structure analysis. The data reveal a hydrogen bonding pattern that is complementary to a peptide beta-sheet.