Playing with peptides: how to build a supramolecular peptide nanostructure by exploiting helix···helix macrodipole interactions

A novel method to build bicomponent peptide self-assembled monolayers (SAMs) has been developed, by exploiting helix···helix macrodipole interactions. In this work, a peptide-based self-assembled monolayer composed of two helical peptides was immobilized on a gold surface. Specifically, a pyrene-containing octapeptide, devoid of any sulfur atom (A8Pyr), and a hexapeptide, functionalized at the N-terminus with (S,R) lipoic acid, for binding to gold substrates (SSA4WA) via a Au-S linkage, have been employed. Both peptides investigated attain a helical structure, because they are almost exclusively formed by strongly folding inducer C(α)-tetrasubstituted α-amino acids. We demonstrate that the two peptides generate a stable supramolecular nanostructure (a densely packed bicomponent peptide monolayer), where A8Pyr is incorporated into the SSA4WA palisade by exploiting helix···helix macrodipole interactions. The presence of both peptides on the gold surface was investigated by spectroscopic and electrochemical techniques, while the morphology of the monolayer was analyzed by ultra high-vacuum scanning tunnelling microscopy. The composition of the bicomponent SAM on the surface was studied by a combination of electrochemical and spectroscopic techniques. In particular, the amount of Au-S linkages from the sulfur-containing peptides was quantified from reductive desorption of the peptide-based SAM, while the amount of A8Pyr was estimated by fluorescence spectroscopy. The antiparallel orientation of the A8Pyr and SSA4WA peptide chains minimizes the interaction energy between the helix dipoles, suggesting that this kind of electrostatic phenomenon is the driving force that stabilizes the bicomponent SAM.     

Hierarchical clustering analysis of flexible GBR 12909 dialkyl piperazine and piperidine analogs

Pharmacophore modeling of large, drug-like molecules, such as the dopamine reuptake inhibitor GBR 12909, is complicated by their flexibility. A comprehensive hierarchical clustering study of two GBR 12909 analogs was performed to identify representative conformers for input to three-dimensional quantitative structure–activity relationship studies of closely-related analogs. Two data sets of more than 700 conformers each produced by random search conformational analysis of a piperazine and a piperidine GBR 12909 analog were studied. Several clustering studies were carried out based on different feature sets that include the important pharmacophore elements. The distance maps, the plot of the effective number of clusters versus actual number of clusters, and the novel derived clustering statistic, percentage change in the effective number of clusters, were shown to be useful in determining the appropriate clustering level.Six clusters were chosen for each analog, each representing a different region of the torsional angle space that determines the relative orientation of the pharmacophore elements. Conformers of each cluster that are representative of these regions were identified and compared for each analog. This study illustrates the utility of using hierarchical clustering for the classification of conformers of highly flexible molecules in terms of the three-dimensional spatial orientation of key pharmacophore elements.     

Electronic Properties of Mono‐Substituted Tetraferrocenyl Porphyrins in Solution and on a Gold Surface: Assessment of the Influencing Factors for Photoelectrochemical Applications

Two unsymmetric meso‐tetraferrocenyl‐containing porphyrins of general formula Fc₃(FcCOR)Por (Fc=ferrocenyl, R=CH₃ or (CH₂)₅Br, Por=porphyrin) were prepared and characterized by a variety of spectroscopic methods, whereas their redox properties were investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) approaches. The mixed‐valence [Fc₃(FcCOR)Por]ⁿ⁺ (n=1,3) were investigated using spectroelectrochemical as well as chemical oxidation methods and corroborated with density functional theory (DFT) calculations. Inter‐valence charge‐transfer (IVCT) transitions in [Fc₃(FcCOR)Por]⁺ were analyzed, and the resulting data matched closely previously reported complexes and were assigned as Robin–Day class II mixed‐valence compounds. Self‐assembled monolayers (SAMs) of a thioacetyl derivative (Fc₃(FcCO(CH₂)₅SCOCH₃)Por) were also prepared and characterized. Photoelectrochemical properties of SAMs in different electrolyte systems were investigated by electrochemical techniques and photocurrent generation experiments, showing that the choice of electrolyte is critical for efficiency of redox‐active SAMs.     

Transition-metal complexes with bidentate ligands spanning trans-position. Part XVI. X-ray structural and 31P-NMR solution studies of 2,11-Bis(diethylphosphinomethyl)benzo[c]phenanthrenesilver(I) perchlorate

The preparation of complexes {AgX(1c)} (X ? Cl, Br, I, NO₃ and ClO₄; 1c = 2,11-bis(diethylphosphinomethyl)benzo[c]phenanthrene) is reported. The ³¹P-NMR spectra of the above complexes were recorded and the ¹J(¹⁰⁷Ag, ³¹P) values are compared with the corresponding data for related complexes. The X-ray crystal structure of [Ag(1c)](ClO₄) was determined. There are two crystallographically independent molecules in the unit cell each containing two-coordinate silver, the O-atoms of the perchlorate anions being outside bonding range from the central atom. The two molecules, however, show different bonding parameters: Thus for ‘molecule 1’ P(1)? Ag(1)? P(2) = 167.6(1)°, Ag(1)? P(1) = 2.389(3) and Ag(1)? P(2) = 2.393(3) Å, while for ‘molecule 2’ P(3)? Ag(2)? P(4) = 164.8(1)°, Ag(2)? P(3) = 2.377(3), and Ag(2)? P(4) = 2.378(3) Å. These differences are probably due to packing forces in the crystal lattice.     

A molecular electrostatic-potential study of acesulfame

Molecular electrostatic-potential maps are reported for the anionic and neutral forms of acesulfame (6-methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide), a sweetener structurally similar to saccharin. The maps generated by methods based on a minimum basis set (STO-3G) and on a polarization basis set (3-21G*) are almost identical with respect to their contour levels. From the contour maps, broad and deep electrostatic-potential minima were found near the SO₂ and NC=O functionalities in the anion. The electrostatic potential minima directly correspond to the reactive sites proposed by Jakinovich for the interaction fo saccharin with its receptor.     

A conformational study of a biologically active conjugated syn-oxime

The conjugated system (E)-tiglaldoxime is the simplest example of a perillartine analog which exhibits sweetness with a taste potency greater than sucrose with almost no bitter aftertaste. In previous studies, the structure of this biologically active compound has been assumed to be planar with the C?C double bond trans to the C?N bond of the oxime moiety. In this article a conformational analysis of this molecule is reported. The results indicate that, although the trans conformer of the planar molecule is indeed the global minimum, other conformers lie within a few kilocalories of this minimum. Hence, other accessible conformations may be available for interaction with the receptor and, therefore, may be biologically active. The structural parameters obtained for this conjugated syn-oxime are nearly identical to those of (E)-acetaldoxime. This fact has implications for the transferability of these parameters to the more complicated perillartine analogs.     

Transition metal complexes with bidentate ligands spanning trans-positions. VI. The preparation of some diaryl- and dialkyl derivatives of 2,11-bis (phosphinomethyl)benzo [c]phenanthrene

The preparation of the ditertiary phosphines 2,11-bis (di-m-tolylphosphinomethyl)benzo [c]phenanthrene ( 1b ), 2,11-bis (di-p-anisylphosphinomethyl)benzo-[c]phenanthrene ( 1c ), 2,11-bis (di-m-trifluoromethylphenylphosphinomethyl) benzo-[c]phenanthrene ( 1d ), 2,11-bis (dicyclohexylphosphinomethyl)benzo [c]phenanthrene ( 1e ) and 2,11-bis [di-(t-butyl)phosphinomethyl]benzo [c]phenanthrene ( 1f ), by a combination of synthetic routes is described.     

Transition metal complexes with bidentate ligands spanning trans-positions part XV X-ray structural and 31P-NMR solution studies of some three-coordinate silver complexes of 2,11-bis[di(tert-butyl)phosphinomethyl]benzo[c]phenathrene and related ligands

A series of three-coordinate bis(dialkylphosphinomethyl)benzo[c]phenanthrene Ag(I) complexes, alkyl= t-Bu, (1b) , and cyclohexyl, (1c) , anion = BF₄, CIO₄, CIO₄, NO₃, Cl, Br, I, have been prepared and thier ³¹ P-NMR characteristics recorded. The solid state structures of [Ag( 1b )Br], [Ag( 1b )Cl] and [Ag( 1b )CIO₄] have been determined by X-ray diffraction. The Ag atom in these complexes shows distorted trigonal geometry. Selected bond lengths and angles are as follows: Ag-P = 2.463(4) Å and 2.433(5) Å, P-Ag-P=141.6(2)° in the bromo complex, Ag-P = 2.457(2) Å and 2.427(2) Å, P-Ag-P = 142.6(1)° ion the chloro complex, and Ag-P = 2.394(2) and 2.393 (2) Å, P-AG-P = 161.5(1)° in the perchlorato complex.     

Synthesis and X-Ray Crystal Structure of an Optically Pure Tripodal C3-Symmetric Tritertiary Phosphine Bearing Chirality on Phosphorus

The preparation of the optically pure tritertiary phosphine (RRR)-MeSi(CH2P(t-Bu)Ph)3 (2) is reported. The route followed involves deprotonation of optically pure (R)-P(BH3)Me(t-Bu)PH (2) the reaction of the resulting carbanion with MeSiCl3, followed by removal with morpholine of the BH3-protecting groups from the triertiary phosphine-borane 3 . The latter's X-ray crystal structure and that of [Rh(NBD)((RRR)- 1 ]TOf)( 4 ), are also rported. Furthermore, it is shown that the separation of the racemic phosphine-borane 2 can be conveniently carried out using medium-pressure liquid chromatgrapy with cellulose-riacetate as a chiral stationary phase.