Copper(II) complexes of terminally protected pentapeptides containing three histidyl residues in alternating positions, Ac-His-Xaa-His-Yaa-His-NH2

Copper(II) complexes of the pentapeptides Ac-HisAlaHisValHis-NH2, Ac-HisValHisAlaHis-NH2, Ac-HisProHisAlaHis-NH2, Ac-HisAlaHisProHis-NH2, Ac-HisGlyHisValHis-NH2 and Ac-HisValHisGlyHis-NH2 have been studied by potentiometric, UV-Vis, CD and EPR spectroscopic methods. It has been found that the pentapeptides are efficient ligands for the complexation with copper(II) and exhibit an outstanding versatility in the co-ordination geometry of complexes. The presence of three histidyl residues provides a high possibility for the formation of macrochelates via the exclusive binding of imidazole-N donor atoms. The macrochelation suppresses, but cannot preclude the deprotonation and metal ion co-ordination of amide functions and the species [CuH(-2)L] and [Cu2H(-4)L] predominate at physiological pH in equimolar solutions and in the presence of excess metal ions, respectively. It is also clear from the data that both C-terminal and internal histidyl residues can work as the anchoring sites for metal binding and subsequent amide deprotonation resulting in the formation of co-ordination isomers and dinuclear species in equimolar solutions and in the presence of excess metal ions, respectively. In more alkaline solutions (pH approximately 10) a third amide function can be deprotonated and co-ordinated in the species [CuH(-3)L]- with (N-,N-,N-,N(im)) co-ordination. The dinuclear species [Cu2H(-5)L]- and [Cu2H(-6)L](2-) containing hydroxide ions and/or imidazolato bridges are formed at high pH in the presence of excess of metal ions. The insertion of one proline into the sequence preceding histidyl residues hinders the deprotonation of amide functions at that site and the formation of only mononuclear complexes was observed with these peptides.     

Polynuclear bismuth-oxo clusters: insight into the formation process of a metal oxide

The reaction of the bismuth silanolates [Bi(OSiR2R')3] (R = R' = Me, Et, iPr; R = Me, R' = tBu) with water has been studied. Partial hydrolysis gave polynuclear bismuth-oxo clusters whereas amorphous bismuth-oxo(hydroxy) silanolates were obtained when an excess of water was used in the hydrolysis reaction. The metathesis reaction of BiCl3 with NaOSiMe3 provided mixtures of heterobimetallic silanolates. The molecular structures of [Bi18Na4O20(OSiMe3)18] (2), [Bi33NaO38(OSiMe3)24].3 C7H8 (3.3 C7H8), [Bi50Na2O64(OH)2(OSiMe3)22].2 C7H8.2H2O (4.2 C7H8.2 H2O), [Bi4O2(OSiEt3)8] (5), [Bi9O7(OSiMe3)13].0.5 C7H8 (6. 0.5C7H8), [Bi18O18(OSiMe3)18)].2C7H8 (7. 2C7H8) and [Bi20O18(OSiMe3)24].3C7H8 (8.3C7H8) are presented and compared with the solid-state structures of [Bi22O26(OSiMe2tBu)14] (9) and beta-Bi2O3. Compound 2 crystallises in the triclinic space group P1 with the lattice constants a = 17.0337(9), b = 19.5750(14), c = 26.6799(16) A, alpha = 72.691(4), beta = 73.113(4) and gamma = 70.985(4) degrees ; compound 3.3C7H8 crystallises in the monoclinic space group P2(1)/n with the lattice constants a = 20.488(4), b = 22.539(5), c = 26.154(5) A and beta = 100.79(3) degrees ; compound 4.2C7H82 H2O crystallises in the monoclinic space group P2(1)/n with the lattice constants a = 20.0518(12), b = 24.1010(15), c = 27.4976(14) A and beta = 103.973(3) degrees ; compound 5 crystallises in the monoclinic space group P2(1)/c with the lattice constants a = 25.256(5), b = 15.372(3), c = 21.306(4) A and beta = 113.96(3) degrees ; compound 6.0.5C7H8 crystallises in the triclinic space group P1 with the lattice constants a = 15.1916(9), b = 15.2439(13), c = 22.487(5) A, alpha = 79.686(3), beta = 74.540(5) and gamma = 66.020(4) degrees ; compound 7.2C7H8 crystallises in the triclinic space group P1 with the lattice constants a = 14.8295(12), b = 16.1523(13), c = 18.4166(17) A, alpha = 75.960(4), beta = 79.112(4) and gamma = 63.789(4) degrees ; and compound 8.3C7H8 crystallises in the triclinic space group P1 with the lattice constants a = 17.2915(14), b = 18.383(2), c = 18.4014(18) A, alpha = 95.120(5), beta = 115.995(5) and gamma = 106.813(5) degrees . The molecular structures of the bismuth-rich compounds are related to the CaF2-type structure. Formally, the hexanuclear [Bi6O8]2+ fragment might be described as the central building unit, which is composed of bismuth atoms placed at the vertices of an octahedron and oxygen atoms capping the trigonal faces. Depending on the reaction conditions and the identity of R, the thermal decomposition of the hydrolysis products [Bi(n)O(l)(OH)(m-)(OSiR3)(3n-(2l-m))] gives alpha-Bi2O3, beta-Bi2O3, Bi12SiO20 or Bi4Si3O12.     

Microsolvation effects on the pi*<--pi electronic transitions in simple aromatic chromophores: the role of the Slater-type Gaussian orbitals in the complete active space self-consistent field approach

One of the most studied feature of aromatic molecular clusters in the gas phase is the shift of the pi*<--pi electronic transitions between the bare aromatic chromophore and its clusters. In the present ab initio complete active space self-consistent field study the coupling of the basis set superposition error and counterpoise procedure and a combination of Pople- and Slater-type Gaussian basis sets has been proven to reproduce quantitatively the gas-phase experimental shifts. The quantal results are here analyzed with respect to the electrostatic and polarization forces and electron density differences, and connected with the sign of the shifts of the electronic transitions.     

Peptide-Functionalized Silk Fibers as a Platform to Stabilize Gelatin for Use in Ingestible Devices

The combination of pharmacologic and endoscopic therapies is the gold standard for treating intestinal failures. The possibility of chemical solubility in water is mandatory for intelligent capsules. Functionalised silk fibroin with peptides and covalently linking different molecular entities to its structure make this protein a platform for preparing gels dissolving in the small and large intestine for drug delivery. In the present study, we linked a peptide containing the cell-adhesive motif Arginine–Glycine–Aspartic acid (RGD) to degummed silk fibres (DSF). Regenerated silk fibroin (RS) films obtained by dissolving functionalised DSF in formic acid were used to prepare composite gelatin. We show that such composite gelatin remains stable and elastic in the simulated gastric fluid (SGF) but can dissolve in the small and large intestines’ neutral-pH simulated intestine fluid (SIF). These findings open up the possibility of designing microfabricated and physically programmable scaffolds that locally promote tissue regeneration, thanks to bio-enabled materials based on functionalised regenerated silk.     

Correlative Cellular Mass Spectrometry Imaging and Amperometry Show Dose Dependent Changes in Lipid Composition and Exocytosis

Aberrant functioning of the proteasome has been associated with crucial pathologic conditions including neurodegeneration. Yet, the complex underlying causes at the cellular level remain unclear and there are conflicting reports of neuroprotective to neurodegenerative effects of proteasomal inhibitors such as lactacystin that are utilised as models for neurodegenerative diseases. The conflicting results may be associated with different dose regimes of lactacystin and hence we have performed a dose dependent study of the effects of lactacystin to identify concurrent changes in the cell membrane lipid profile and the dynamics of exocytosis using a combination of surface sensitive mass spectrometry and single cell amperometry. Significant changes of negatively charged lipids were associated with different lactacystin doses that showed a weak correlation with exocytosis while changes in PE and PE−O lipids showed dose dependent changes correlated with initial pore formation and total release of vesicle content respectively.