Exceptional adhesive and gelling properties of fibrous nanoscopic tapes of self-assembled bipolar urethane amides of L-phenylalanine

Seven L-phenylalanine based alkyl (monopolar) and alkanediyl (bipolar) derivatives are synthesized; while the bipolar urethane amides form gels and show strong adhesive properties, the monopolar analogues form fibrous nanoscopic cloth-like tapes.

Impressive Gelation in Organic Solvents by Synthetic, Low Molecular Mass, Self-Organizing Urethane Amides of L-Phenylalanine

Synthetic routes leading to 12 L-phenylalanine based mono- and bipolar derivatives (1-12) and an in-depth study of their structure-property relationship with respect to gelation have been presented. These include monopolar systems such as N-[(benzyloxy)carbonyl]-L-phenylalanine-N-alkylamides and the corresponding bipolar derivatives with flexible and rigid spacers such as with 1,12-diaminododecane and 4,4'-diaminodiphenylmethane, respectively. The two ends of the latter have been functionalized with N-[(benzyloxy)carbonyl]-L-phenylalanine units via amide connection. Another bipolar molecule was synthesized in which the middle portion of the hydrocarbon segment contained polymerizable diacetylene unit. To ascertain the role of the presence of urethane linkages in the gelator molecule protected L-phenylalanine derivatives were also synthesized in which the (benzyloxy)carbonyl group has been replaced with (tert-butyloxy)carbonyl, acetyl, and benzoyl groups, respectively. Upon completion of the synthesis and adequate characterization of the newly described molecules, we examined the aggregation and gelation properties of each of them in a number of solvents and their mixtures. Optical microscopy and electron microscopy further characterized the systems that formed gels. Few representative systems, which showed excellent gelation behavior was, further examined by FT-IR, calorimetric, and powder X-ray diffraction studies. To explain the possible reasons for gelation, the results of molecular modeling and energy-minimization studies were also included. Taken together these results demonstrate the importance of the presence of (benzyloxy)carbonyl unit, urethane and secondary amide linkages, chiral purities of the headgroup and the length of the alkyl chain of the hydrophobic segment as critical determinants toward effective gelation.

N-Urethane-Protected Amino Alkyl Isothiocyanates: Synthesis, Isolation, Characterization, and Application to the Synthesis of Thioureidopeptides

Synthetically useful N-Fmoc amino-alkyl isothiocyanates have been described, starting from protected amino acids. These compounds have been synthesized in excellent yields by thiocarbonylation of the monoprotected 1,2-diamines with CS2/TEA/p-TsCl, isolated as stable solids, and completely characterized. The procedure has been extended to the synthesis of amino alkyl isothiocyanates from Boc- and Z-protected amino acids as well. The utility of these isothiocyanates for peptidomimetics synthesis has been demonstrated by employing them in the preparation of a series of dithioureidopeptide esters. Boc-Gly-OH and Boc-Phe-OH derived isothiocyanates 9a and 9c have been obtained as single crystals and their structures solved through X-ray diffraction. They belong to the orthorhombic crystal system, and have a single molecule in the asymmetric unit (Z′ = 1). 9a crystallizes in the centrosymmetric space group Pbca, while 9c crystallizes in the noncentrosymmetric space group P212121.

Infrared studies on the conformation of synthetic alamethicin fragments and model peptides containing .alpha.-aminoisobutyric acid

ABSTRACT: Infrared studies of synthetic alamethicin fragments and model peptides containing a-aminoisobutyric acid (Aib) have been carried out in solution. Tripeptides and larger fragments exhibit a strong tendency to form /3 turns, stabilized by 4 - 1 10-atom hydrogen bonds. Dipeptides show less well-defined structures, though C5 and C7 conformations are detectable. Conformational restrictions imposed by Aib residues result in these peptides populating a limited range of states. Integrated intensities of the hydrogen-bonded N-H stretching band can be used to quantitate the number of intramolecular hydrogen bonds. Predictions made from infrared data are in excellent agreement with nuclear magnetic resonance and X-ray diffraction studies. Assignments of the urethane and tertiary amide carbonyl groups in the free state have been made in model peptides. Shifts to lower frequency on hydrogen bonding are observed for the carbonyl groups. The 1-6 segment of alamethicin is shown to adopt a 310 helical structure stabilized by four intramolecular hydrogen bonds. The fragments Boc-Leu-Aib-Pro-Val-Aib-OMe (1 2-1 6) and Boc-Gly-Leu-Aib-Pro-Val-Aib-OMe (1 1-1 6) possess structures involving 4 - 1 and 5 - 1 hydrogen bonds. Supporting evidence for these structures is obtained from proton nuclear magnetic resonance studies.

The crystal and molecular structure of benzyloxycarbonyl-a-amino-isobutyryl-L-prolyl-methylamide. The observation of an X2-Pro3 Type III b-turn

The crystal and molecular structure of N-benzyloxycarbonyl-a-aminoisobutyryl-L-prolyl methylamide, the amino terminal dipeptide fragment of alamethicin, has been determined using direct methods. The compound crystallizes in the orthorhombic system with the space group P212-21. Cell dimensions are a = 7.705 A, b = 11.365 A, and c = 21.904 A. The structure has been refined using conventional procedures to a final R factor of 0.054. The molecular structure possesses a 4 - 1 intramolecular N-H--0 hydrogen bond formed between the CO group of the urethane moiety and the NH group of the methylamide function. The peptide backbone adopts the type 111 P-turn conformation, with 42 = -51.0°, +* = -39.7",&j = -65.0', $3 = -25.4'. An unusual feature is the occurrence of the proline residue at position 3 of the P-turn. The observed structure supports the view that Aib residues initiate the formation of type 111 @-turn conformations. The pyrrolidine ring is puckered in Cy-exo fashion.

H N.M.R. studies of protected alpha-aminoisobutyric acid containing peptides. Chemical shift nonequivalence of benzyloxycarbonyl methylene protons

The benzylic methylene protons in a large number of benzyloxycarbonyl alpha-aminoisobutyric acid (Z-Aib) containing peptides, show chemical shift nonequivalence. The magnitude of the geminal nonequivalence is correlated with the involvement of the urethane carbonyl group, in an intramolecular hydrogen bond. Studies of the model compounds Z-Aib-Aib-Ala-NHMe, and Z-Aib-Aib-Aib-Pro-OMe clearly establish the presence of intramolecular hydrogen bonds, involving the urethane CO group. In both compounds marked anisochrony of the benzylic methylene protons is demonstrated. In Z-Aib-Aib-Pro-OMe, where a 4 leads to 1 hydrogen bonded beta-turn is not possible, the benzylic-CH2-protons appear as a singlet in CDCl3 and have a very small chemical shift difference in (CD3)2SO. The observation of such nonequivalence is of value in establishing whether the amino terminal Aib-Pro beta-turn is retained in large peptide-fragments of alamethicin.

Chemical toughening of epoxies. I. Structural modification of epoxy resins by reaction with hydroxy-terminated poly (butadiene-co-acrylonitrile)

In an attempt to toughen the epoxy resin matrix for fiber-reinforced composite applications, a chemical modification procedure of a commercially available bisphenol-A-based epoxy resin using reactive liquid rubber HTBN [hydroxy-terminated poly(butadiene-co-acrylonitrile)] and TDI (tolylene diisocyanate) is described. The progress of the reaction and the structural changes during modification process are studied using IR spectroscopy, viscosity data, and chemical analysis (epoxy value determination). The studies support the proposition that TDI acts as a coupling agent between the epoxy and HTBN, forming a urethane linkage with the former and an oxazolidone ring with the latter. The chemical reactions that possibly take place during the modification are discussed.

Chemical toughening of epoxies. I. Structural modification of epoxy resins by reaction with hydroxy-terminated poly(butadiene-co-acrylonitrile)

In an attempt to toughen the epoxy resin matrix for fiber-reinforced composite applications, a chemical modification procedure of a commercially available bisphenol-A-based epoxy resin using reactive liquid rubber HTBN [hydroxy-terminated poly(butadiene-co-acrylonitrile)] and TDI (tolylene diisocyanate) is described. The progress of the reaction and the structural changes during modification process are studied using IR spectroscopy, viscosity data, and chemical analysis (epoxy value determination). The studies support the proposition that TDI acts as a coupling agent between the epoxy and HTBN, forming a urethane linkage with the former and an oxazolidone ring with the latter. The chemical reactions that possibly take place during the modification are discussed.

Hybridization of carbon-glass epoxy composites: An approach to achieve low coefficient of thermal expansion at cryogenic temperatures

The paper is based on a study to develop carbon-glass epoxy hybrid composites with desirable thermal properties for applications at cryogenic temperatures. It analyzes the coefficient of thermal expansion of carbon-epoxy and glass-epoxy composite materials and compares it with the properties of carbon-glass epoxy hybrid composites in the temperature range 300 K to 125K. Urethane modified epoxy matrix system is used to make the composite specimens suitable for use even for temperatures as low as 20K. It is noted that the lay-up with 80% of carbon fibers in the total volume fraction of fibers oriented at 30 degrees and 20% of glass fibers oriented at 0 degrees yields near to zero coefficient of thermal expansion as the temperature is lowered from ambient to 125 K. (c) 2010 Elsevier Ltd. All rights reserved.

Structure of N-tert-butyloxycarbonyl-[alpha]-aminoisobutyryl-DL-pipecolyl-[alpha]-aminoisobutyric acid methyl ester

C20H35N3O6 (Boc-Aib-DL-Pip-Aib-OMe, Boc = tert-butyloxycarbonyl, Aib = alpha-aminoisobutyric acid, Pip = pipecolic acid, OMe = methoxy), M(r) = 413.5, monoclinic, P2(1)/c, a = 18.055 (3), b = 15.048 (3), c = 17.173 (3) angstrom, beta = 91.7 (1)-degrees, V = 4663.8 (9) angstrom3, Z = 8, D(m) = 1.16, D(x) = 1.178 Mg m-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 0.081 mm-1, F(000) = 1792, T = 297 K. The final R value for 4925 [I greater-than-or-equal-to 3sigma(I)] reflections is 0.065 (wR = 0.067). The peptide backbone of the two independent molecules in the asymmetric unit is folded at the -Aib-Pip- sequence to form a type-I (I') beta-bend stabilized by a 1 <-- 4 intramolecular N-H...O=C hydrogen bond between the Aib(3) peptide N-H and Boc urethane C=O groups.

Glycidyl azide polymer crosslinked through triazoles by click chemistry: curing, mechanical and thermal properties

Glycidyl azide polymer (GAP) was cured through click chemistry by reaction of the azide group with bispropargyl succinate (BPS) through a 1,3-dipolar cycloaddition reaction to form 1,2,3-triazole network. The properties of GAP-based triazole networks are compared with the urethane cured GAP-systems. The glass transition temperature (T-g), tensile strength, and modulus of the system increased with crosslink density, controlled by the azide to propargyl ratio. The triazole incorporation has a higher T-g in comparison to the GAP-urethane system (T-g-20 degrees C) and the networks exhibit biphasic transitions at 61 and 88 degrees C. The triazole curing was studied using Differential Scanning Calorimetry (DSC) and the related kinetic parameters were helpful for predicting the cure profile at a given temperature. Density functional theory (DFT)-based theoretical calculations implied marginal preference for 1,5-addition over 1,4-addition for the cycloaddition between azide and propargyl group. Thermogravimetic analysis (TG) showed better thermal stability for the GAP-triazole and the mechanism of decomposition was elucidated using pyrolysis GC-MS studies. The higher heat of exothermic decomposition of triazole adduct (418kJmol(-1)) against that of azide (317kJmol(-1)) and better mechanical properties of the GAP-triazole renders it a better propellant binder than the GAP-urethane system.

Azide and Alkyne Terminated Polybutadiene Binders: Synthesis, Cross-linking, and Propellant Studies

In composite solid propellants, the fuel and oxidizer are held together by a polymer binder. Among the different types of polymeric binders used in solid propellants, hydroxyl terminated polybutadiene (HTPB) is considered as the most versatile. HTPB is conventionally cured using isocyanates to form polyurethanes. However, the incompatibility of isocyanates with energetic oxidizers such as ammonium dinitramide and hydrazinium nitroformate, the short pot life of the propellant slurry, and undesirable side reactions with moisture are limiting factors which adversely affect the mechanical properties of HTPB based propellant. With an aim of resolving these problems, HTPB was chemically transformed to azidoethoxy carbonyl amine terminated polybutadiene and propargyloxy carbonyl amine terminated polybutadiene by adopting appropriate synthesis strategies and characterizing them by spectroscopic and chromatographic techniques. This is the first report on 1,3-dipolar addition reaction involving azide and alkyne end groups for cross-linking HTPB. The blend of these two polymers underwent curing under mild temperature (60 degrees C) conditions through 1,3-dipolar cycloaddition reaction resulting in triazoletriazoline networks. The curing parameters were studied using differential scanning calorimetry. The kinetic parameter, viz., activation energy, was computed to be 107.6 kJ/mol, the preexponential factor was 2.79 x 10(12) s-(1), and the rate constant at 60 degrees C was computed to be 3.64 x 10-(5) s-(1). The cure profile at a given temperature was predicted using the kinetic parameters. Rheological studies revealed that the gel time for curing through the 1,3-dipolar addition is 280 min compared to 120 min for curing through the urethane route. The mechanical properties of the resultant cured polybutadiene network were superior to those of polyurethanes. The cured triazolinetriazole polymer network exhibited biphasic morphology with two glass transitions (T-g) at -56 and 42 degrees C in contrast to the polyurethane which exhibited a single transition at -60 degrees C. This was corroborated by associated morphological changes observed by scanning probe microscopy. The propellant processed using this binder has the advantages of improved pot life as indicated by the end of the mix viscosity which is 165 Pas as compared with 352 Pas for the polyurethane system along with a slow build- up rate. The mechanical properties of the propellant are superior to polyurethane with an improvement of 14% in tensile strength, 22% enhancement in elongation at break, and 12% in modulus.

Inter molecular azide-diisocyanate coupling: new insights for energetic solid propellants

Hydroxyl terminated azide binders can undergo a spurious reaction with diisocyanates to form tetrazoline-5-one via an inter molecular 1,3-dipolar cycloaddition reaction apart from urethane/allophanate groups which has been overlooked. This has serious implications on solid propellants. The computed activation barrier using density functional theory (DFT) for urethane formation reaction is 28.4 kJ mol(-1) and that for tetrazoline-5-one formation reaction is 108.0 kJ mol(-1). DFT studies reveal that the rate limiting step of the reaction is 1,3-dipolar cycloaddition between azide and isocyanate. A dual cure was observed in the temperature ranges 42-77 degrees C and 78-146 degrees C by differential scanning calorimetry (DSC) and rheological studies, confirming multiple reactions. Tetrazoline-5-one formation was confirmed by Fourier transform infrared spectroscopy (FTIR) and solid state nuclear magnetic resonance spectroscopy (NMR).

A Facile Synthesis of 1,5-Disubstituted Tetrazole Peptidomimetics by Desulfurization/Electrocyclization of Thiopeptides

The cis-amide bond isostere, 1,5-disubstituted tetrazole,has been introduced in the peptide backbone by a simple route starting from the thiopeptide. The desired 1,5-disubstituted tetrazole peptidomimetics were synthesized by the desulfurization of thiopeptides by using HgCl2 in the presence of NaN3/TEA in DMF in good yields. Various other thiophilic reagents including hypervalent iodine reagents failed to deliver the tetrazole product with the exception of CBr4/PPh3, which resulted in moderate yields. The advantage of the present protocol over previous methods has been demonstrated by the selective insertion of tetrazole into peptide-thiopeptide hybrids. Also, the protocol is compatible with commonly employed urethane protecting groups (Fmoc, Boc, and Cbz) in peptide chemistry. Thiopeptide Boc-Pro-CSNH]-Val-OMe (2i) and two tetrazole peptidomimetics Cbz-Ala-CN4]-Phe-OMe (3d) and Boc-Pro-CN4]-Val-OMe (3i) were obtained as single crystals and their molecular structures have been confirmed by X-ray crystallography.