A new molecular scaffold for the formation of supramolecular peptide double helices: the crystallographic insight

A series of water-soluble synthetic dipeptides (1-3) with an N-terminally located beta-alanine residue, beta-alanyl-L-valine (1), beta-alanyl-L-isoleucine (2), and beta-alanyl-L-phenylalanine (3, form hydrogen-bonded supramolecular double helices with a pitch length of 1 nm, whereas the C-terminally positioned beta-alanine containing dipeptide (4), L-phenylalanyl-beta-alanine, does not form a supramolecular double helical structure. beta-Ala-Xaa (Xaa = Val/Ile/Phe) can be regarded as a new motif for the formation of supramolecular double helical structures in the solid state.

Overlapping double turn conformations adopted by tetrapeptides containing non-coded alpha-Amino Isobutyric Acid (AIB) and formation of tape-like structures through supramolecular helix mediated self-assembly

Single crystal X-ray diffraction studies and solvent dependent H-1 NMR titrations reveal that a set of four tetrapeptides with general formula Boc-Xx(1)-Aib(2)-Yy(3)-Zz(4)-OMe, where Xx, Yy and Zz are coded L- amino acids, adopt equivalent conformations that can be described as overlapping double turn conformations stabilized by two 4 -> 1 intramolecular hydrogen bonds between Yy(3)-NH and Boc C=O and Zz(4)-NH and Xx(1)C=O. In the crystalline state, the double turn structures are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. Field emission scanning electron microscopic (FE-SEM) images of the tetrapeptides in the solid state reveal that they can form flat tape-like structures. The results establish that synthetic Aib containing supramolecular helices can form highly ordered self-aggregated amyloid plaque like human amylin.

Design of supramolecular beta-sheet forming beta-turns containing aromatic rings and non-coded alpha-aminoisobutyric acid and the formation of flat fibrillar structures through self-assembly

Single crystal X-ray diffraction studies show that the three designed tripeptides Boc-Leu-Aib-m-NA-NO2 (I), Boc-Phe-Aib-m-NA-NO2 (II) and Boc-Pro-Aib-m-ABA-OMe (III) (Aib, -aminoisobutyric acid; m-NA, m-nitroaniline; m-ABA, m-aminobenzoic acid; Boc, t-butyloxycarbonyl) containing aromatic rings in the backbones adopt -turn structures that are self-assembled through intermolecular hydrogen bonds and van der Waals interactions to create layers of -sheets. Solvent-dependent NMR titration and CD studies show that the -turn structures of the peptides also exist in the solution phase. The field emission scanning electron microscopic and transmission electron microscopic images of the peptides in the solid state reveal fibrillar structures of flat morphology that are formed through -sheet mediated self-assembly of the preorganised -turn building blocks.

Self-assembly of beta-turn forming synthetic tripeptides into supramolecular beta-sheets and amyloid-like fibrils in the solid state

We have described here the self-assembling properties of the synthetic tripeptides Boc-Ala(1)-Aib(2) -Val (3)-OMe 1, BocAla(l)-Aib(2)-Ile(3)-OMe 2 and Boc-Ala(l)-Gly(2)-Val(3)-OMe 3 (Aib=alpha-arnino isobutyric acid, beta-Ala=beta-alanine) which have distorted beta-turn conformations in their respective crystals. These turn-forming tripeptides self-assemble to form supramolecular beta-sheet structures through intermolecular hydrogen bonding and other noncovalent interactions. The scanning electron micrographs of these peptides revealed that these compounds form amyloid-like fibrils, the causative factor for many neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Prion-related encephalopathies. (C) 2004 Elsevier Ltd. All rights reserved.

Different supramolecular hydrogen bond structures and significant changes in magnetic properties in dinuclear mu(2)-1,1-N-3 copper(II) complexes with very similar tridentate Schiff base blocking ligands

Three new basal-apical, mu(2)-1,1-azide bridged complexes, [CuL1(N-3)](2) (1), [CuL2(N-3)](2) (2) and [CuL3(N-3)]2 (3) with very similar tridentate Schiff base blocking ligands [L-1=N-(3-aminopropyl) salicylaldimine, L-2=7-amino-4-methyl-5-azahept-3-en-2-one and L-3=8-amino-4-methyl-5-azaoct-3-en-2-one) have been synthesised and their molecular structures determined by X-ray crystallography. In complex 1, there is no inter-dimer H-bonding. However, complexes 2 and 3 form two different supramolecular structures in which the dinuclear entities are linked by strong H-bonds giving one-dimensional systems. Variable-temperature (300-2 K) magnetic susceptibility measurements and magnetization measurements at 2 K reveal that complexes 1 and 2 have antiferromagnetic coupling while 3 has ferromagnetic coupling which is also confirmed by EPR spectra at 4-300 K. Magnetostructural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds in complexes 2 and 3.

Supramolecular hydrogen-bond structures and magnetic interactions in basal-apical, dinuclear, azide-bridged copper(II) complexes

The synthesis, characterisation, X-ray single crystal structures and magnetic properties of three new basal-apical mu(2)-1,1-azide-bridged complexes [(CuLN3)-N-1](2) (1), [(CuLN3)-N-2](2) (2) and [(CuLN3)-N-3](2) (3) with very similar tridentate Schiff-base blocking ligands {HL1 = N-[2-(ethylamino) ethyl] salicylaldimine; HL2 = 7-(ethylamino)-4-methyl-5-azahept-3-en-2-one; HL3 = 7-amino-4-methyl-5-azaoct-3-en-2-one} have been reported [complex 1: monoclinic, P2(1)/c, a = 8.390(2), b = 7.512(2), c = 19.822(6) Angstrom, beta = 91.45(5)degrees; complex 2: monoclinic, P2(1)/c, a = 8.070(9), b = 9.787(12), c = 15.743(17) A, beta = 98.467(10)degrees; complex 3: monoclinic, P2(1)/n, a = 5.884(7), b = 16.147(18), c = 11.901(12) Angstrom, beta = 90.050(10)degrees]. The structures consist of neutral dinuclear entities resulting from the pairing of two mononuclear units through end-on azide bridges connecting an equatorial position of one copper centre to an axial position of the other, The copper ions adopt a (4+1) square-based geometry in all the complexes. In complex 2, there is no inter-dimer hydrogen-bonding. However, complexes 1 and 3 form two different supramolecular structures in which the dinuclear entities are linked by H-bonds giving one-dimensional systems. Variable temperature (300-2 K) magnetic-susceptibility measurements and magnetisation measurements at 2 K reveal that all three complexes have antiferromagnetic coupling. Magneto-structural correlations have been made taking into consideration both the azido bridging ligands and the existence of intermolecular hydrogen bonds. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

Supramolecular beta-sheet and nanofibril formation by self-assembling tripeptides containing an N-terminally located gamma-aminobutyric acid residue

Three terminally protected tripeptides Boc-gamma-Abu-Val-Leu-OMe 1, Boc-gamma-Abu-Leu-Phe-OMe 2 and Boc-gamma-Abu-Val-Tyr-OMe 3 (gamma-Abu = gamma-aminobutyric acid) each containing an N-terminally positioned gamma-aminobutyric acid residue have been synthesized, purified and studied. FT-IR studies of all these peptides revealed that these peptides form intermolecularly hydrogen bonded supramolecular beta-sheet structures. Peptides 1, 2 and 3 adopt extended backbone beta-strand molecular structures in crystals. Crystal packing of all these peptides demonstrates that these beta-strand structures self-assemble to form intermolecularly H-bonded parallel beta-sheet structures. Peptide 3 uses a side chain tyrosyl -OH group as an additional hydrogen bonding functionality in addition to the backbone CONH groups to pack in crystals. Transmission electron microscopic studies of all peptides indicate that they self-assemble to form nanofibrillar structures of an average diameter of 65 nm. These peptide fibrils exhibit amyloid-like behavior as they bind to a physiological dye Congo red and show a characteristic green-gold birefringence under polarizing microscope.

Novel supramolecular network in tri- and mono-nuclear oxovanadium(V)-salicyl-hydroximate: Synthesis, structure and catalytic oxidation of hydrocarbons using H2O2 as terminal oxidant

oxovanadium(V) salicylhydroximate complexes, [VO(SHA)(H2O)]center dot 1.58H(2)O (1) and [V3O3(CSHA)(3) (H2O)(3)]center dot 3CH(3)COCH(3) (2) have been synthesized by reaction of VO43- with N-salicyl hydroxamic acid (SHAHS) and N-(5-chlorosalicyl) hydroxamic acid (CSHAH(3)), respectively, in methanol medium. Compound 1 on reaction with pyridine 2,6-dicarboxylic acid (PyDCH2) yields mononuclear complex [VO(SHAH(2))(PyDC)] (3). Treatment of compound 3 with hydrogen peroxide at low pH (2-3) and low temperature (0-5 degrees C) yields a stable oxoperoxovanadium(V) complex H[VO(O-2)(PyDC)(H2O)]center dot 2.5H(2)O (4). All four complexes (1-4) have been characterized by spectroscopic (IR, UV-Vis, V-51 NMR) and single crystal X-ray analyses. Intermolecular hydrogen bonds link complex 1 into hexanuclear clusters consisting of six {VNO5} octahedra surrounded by twelve {VNO5} octahedra to form an annular ring. While the molecular packing in 2 generates a two-dimensional framework hydrogen bonds involving the solvent acetone molecules, the mononuclear complexes 3 and 4 exhibit three-dimensional supramolecular architecture. The compounds 1 and 2 behave as good catalysts for oxygenation of benzylic, aromatic, carbocyclic and aliphatic hydrocarbons to their corresponding hydroxylated and oxygenated products using H2O2 as terminal oxidant; the process affords very good yield and turnover number. The catalysis work shows that cyclohexane is a very easily oxidizable substrate giving the highest turnover number (TON) while n-hexane and n-heptane show limited yield, longer time involvement and lesser TON than other hydrocarbons. (C) 2008 Elsevier Ltd. All rights reserved.

Facile bisurethane supramolecular polymers containing flexible alicyclic receptor units

This paper details the synthesis, characterisation and physical analyses of a series of hydrogen bonded urethane supramolecular polymer systems that are created by a facile one-step synthesis from inexpensive and commercially available starting materials. We report the synthesis and characterisation of a series of low molecular weight bisurethanes (<650 a.m.u.) that exhibit physical properties in the bulk that are characteristic of polyurethane materials possessing far higher molecular weight. The physical characteristics of these low molecular weight bisurethanes were investigated by using temperature-dependent rheological analysis and viscometry and the nature in which these compounds assembled was assessed using IR and NMR spectroscopies. These studies reveal that these simple bisurethanes self-assemble via hydrogen bonding interactions.

Thermally responsive elastomeric supramolecular polymers featuring flexible aliphatic hydrogen-bonding end-groups

The present paper details the synthesis, characterization, and preliminary physical analyses of a series of polyisobutylene derivatives featuring urethane and urea end-groups that enable supramolecular network formation to occur via hydrogen bonding. These polymers are readily accessible from relatively inexpensive and commercially available starting materials using a simple two-step synthetic approach. In the bulk, these supramolecular networks were found to possess thermoreversible and elastomeric characteristics as determined by temperature-dependent rheological analysis. These thermoreversible and elastomeric properties make these supramolecular materials potentially very useful in applications such as adhesives and healable surface coatings.

Proteomic analysis of arginine adducts on glyoxal-modified ribonuclease

Accumulation of advanced glycation end-products (AGEs) on proteins is associated with the development of diabetic complications. Although the overall extent of modification of protein by AGEs is limited, localization of these modifications at a few critical sites might have a significant effect on protein structure and function. In the present study, we describe the sites of modification of RNase by glyoxal under physiological conditions. Arg(39) and Arg(85), which are closest to the active site of the enzyme, were identified as the primary sites of formation of the glyoxal-derived dihydroxyimidazolidine and hydroimidazolone adducts. Lower amounts of modification were detected at Arg(10), while Arg(33) appeared to be unmodified. We conclude that dihydroxyimidazolidine adducts are the primary products of modification of protein by glyoxal, that Arg(39) and Arg(85) are the primary sites of modification of RNase by glyoxal, and that modification of arginine residues during Maillard reactions of proteins is a highly selective process.

Hydrogen bonded supramolecular elastomers : correlating hydrogen bonding strength with morphology and rheology

A series of six low molecular weight elastomers with hydrogen bonding end-groups have been designed, synthesised and studied. The poly(urethane) based elastomers all contained essentially the same hard block content (ca. 11%) and differ only in the nature of their end-groups. Solution state 1H NMR spectroscopic analysis of model compounds featuring the end-groups demonstrate that they all exhibit very low binding constants, in the range 1.4 to 45.0 M-1 in CDCl3, yet the corresponding elastomers each possess a markedly different nanoscale morphology and rheology in the bulk. We are able to correlate small variations of the binding constant of the end-groups with dramatic changes in the bulk properties of the elastomers. These results provide an important insight into the way in which weak non-covalent interactions can be utilized to afford a range of self-assembled polyurethane based materials that feature different morphologies.

A supramolecular polymer based on tweezer-type pi-pi stacking interactions: molecular design for healability and enhanced toughness

An elastomeric, healable, supramolecular polymer blend comprising a chain-folding polyimide and a telechelic polyurethane with pyrenyl end groups is compatibilized by aromatic pi-pi stacking between the pi-electron-deficient diimide groups and the pi-electron-rich pyrenyl units. This interpolymer interaction is the key to forming a tough, healable, elastomeric material. Variable-temperature FTIR analysis of the bulk material also conclusively demonstrates the presence of hydrogen bonding, which complements the pi-pi stacking interactions. Variable-temperature SAXS analysis shows that the healable polymeric blend has a nanophase-separated morphology and that the X-ray contrast between the two types of domain increases with increasing temperature, a feature that is repeatable over several heating and cooling cycles. A fractured sample of this material reproducibly regains more than 95% of the tensile modulus, 91% of the elongation to break, and 77% of the modulus of toughness of the pristine material.

Supramolecular assemblies of metal ions in complex bimetallic and trimetallic salts based on hexacyanoferrate(III) ion

Two complex heterometallic salts with formulae Tl-6[Fe(CN)(6)](1) (33)(NO3)(OH) (1) and [Co(bpy)(2)(CN)(2)](2){[Ag(CN)(2)](0) (5)[Fe(CN)(6)](0) (5)} 8H(2)O (2) have been synthesized and fully characterized Single crystal X-ray analyses reveal that compound 1 is comprised of discrete Tl+ cations and [Fe(CN)(6)](3-) anions together with OH- and NO3- anions Compound 2 contains [Co(bpy)(2)(CN)(2)](+) cations and {[Ag(CN)(2)][Fe(CN)(6)]}(-) anions together with eight molecules of water of crystallization Both structures form unprecedented three-dimensional supramolecular networks via non covalent interactions Another important observation is that the stereochemically active inert (lone) pair present on Tl+ plays little role in controlling the structure of 1 The water molecules in 2 play important roles in providing stability organizing a supramolecular network through hydrogen bonding In the syntheses of 1 and 2 Fe(II) is oxidized to Fe(III) and Co(II) to Co(III) respectively facilitating the formation of the salts that are obtained Both compounds exhibit photoluminescence emission in solution near the visible region.

Construction of supramolecular helices and breaking the helicity by forming supramolecular β-sheet structures using suitable self-assembling pseudopeptide building blocks

Bis-valine derivatives or malonamide (Guha,S.; Drew, M.G.B. Small 2008, 4, 1993-2005) and a bis-valine derivative of 1,1-cyclopropone dicarboxamide were used as building blocks for the construction of supramolecular helical structures. The six-membered intramolecular hydrogen-bonded scaffold is formed, and this acts as a unique supramolecular synthon for the construction of a pseudopeptide-based supramolecular helical structure. However, in absence of this intramolecular hydrogen bond. intermolecular hydrogen bonds are formed among the peptide strands. This leads to a supramolecular beta-sheet structure. Proper selection of the supramolecular synthon (six-membered intramolecular hydrogenbonded scaffold) promotes supramolecular helix formation, and a deviation from this molecular structure dictates the disruption of supramolecular helicity. In this study, six crystal structures have been used to demonstrate that a change in the central angle and/or the central core structure of dicarboxamides can be used to design either a supramolecular helix or a beta-sheet.