Negative ion dissociation of peptides containing hydroxyl side chains

The dissociation of deprotonated peptides containing hydroxyl side chains was studied by electrospray ionization coupled with Fourier transform ion cyclotron resonance (ESI-FTICR) via sustained off-resonance irradiation collision induced dissociation (SORI-CID). Dissociation under post-source decay (PSD) conditions was performed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). This work included hexapeptides with one residue of serine, threonine, or tyrosine and five inert alanine residues. During SORI-CID and PSD, dissociation of [M-H](-) yielded c- and y-ions. Side-chain losses of formaldehyde (HCHO) from serine-containing peptides, acetaldehyde (CH(3)CHO) from threonine-containing peptides, and 4-methylene-2,5-cycohexadienone (C(7)H(6)O) from tyrosine-containing peptides were generally observed in the negative ion PSD and SORI-CID spectra. Side-chain loss occurs much less from tyrosine-containing peptides than from serine- and threonine-containing peptides. This is probably due to the bulky side chain of tyrosine, resulting in steric hindrance and poor geometry for dissociation reactions. Additionally, a selective cleavage leading to the elimination of the C-terminal residue from [M-H](-) was observed from the peptides with serine and threonine at the C-terminus. This cleavage does not occur in the dissociation of peptides with an amide group at the C-terminus or peptides with neutral or basic residues at the C-terminus. It also does not occur with tyrosine at the C-terminus. Both the C-terminal carboxylic acid group and the hydroxyl side chain of the C-terminal residue must play important roles in the mechanism of C-terminal residue loss. A mechanism involving both the C-terminal carboxylic acid group and a hydroxyl side chain of serine and threonine is proposed.     

Effect of phenylalanine on the fragmentation of deprotonated peptides

The fragmentation reactions of a variety of deprotonated dipeptides and tripeptides containing phenylalanine have been studied using energy-resolved collision-induced dissociation, isotopic labeling and MS/MS/MS experiments. The benzyl a-group has a substantial effect on the fragmentation reactions observed. When the phenylalanine is in the C-terminal position of dipeptides or tripeptides a major fragmentation reaction is elimination of neutral cinnamic acid to from a deprotonated amino acid amide (c1 ion) for dipeptides and a deprotonated dipeptide amide (c2 ion) for tripeptides. Fragmentation of the [M - H]- ions of tripeptides with phenylalanine in the central position also results in substantial formation of the deprotonated amide of the N-terminal amino acid residue. When the phenylalanine residue is in the N-terminal position elimination of C7H8 from the [M - H - CO2]- ion and formation of the benzyl anion become important fragmentation pathways. Sequence ions frequently observed are the y1 ions, "b2 ions and a3-Nt ions.     

Collision-Induced dissociations of deprotonated peptides. Dipeptides containing aspartic or glutamic acids

Deprotonated dipeptides, on collisional activation, fragment by the characteristic process NH₂CH(R¹) CONHCH(R²)CO₂^? → NH₂^?C(R¹)CONHCH(R²)CO₂H → ^?NHCH(R²)CO₂H + NH₂C(R¹)?C?O, when R¹ and R² = H or alkyl. However, when one of the constituent amino acids is either aspartic acid or glutamic acid, the standard cleavage becomes minor in comparison with fragmentation through the α-side-chain of Asp or Glu. For example, [Asp-Leu - H]^? and [Leu-Asp - H]^? both fragment principally by loss of water, a fragmentation not normally noted for peptides. In addition, [Leu-Asp - H]^? loses CO₂ and also forms HO₂CCH?CHCO₂^?˙. These fragmentations establish that Asp is the C-terminal amino acid. In contrast, isomeric Glu dipeptides, e.g. [Glu-Ala - H]^? and [Ala-Glu - H]^? undergo similar fragmentation, both competitively losing H₂O and CO₂. Both spectra also contain a product ion at m/z 128, identified as the pyroglutamate anion. Product ion and deuterium-labelling studies have been used in an attempt to elucidate the complex fragmentation mechanisms in these systems.     

Trimeric liquid crystals containing lateral alkyl chains

The first twelve members of the n-alkyl 2,5-bis-(4'-cyanobiphenyloxybutyloxy)-benozates have been prepared. The compounds are nematogenic; in addition the first three members exhibit a smectic A phase. The nematic-isotropic transition temperatures decrease with little or no alternation on increasing the number of methylene groups in the lateral chain; this is analogous to the behaviour found in monomeric and polymeric mesogens possessing lateral alkyl chains.     

Trimeric liquid crystals containing lateral alkyl chains

Abstract

The first twelve members of the n-alkyl 2,5-bis-(4′-cyanobiphenyloxybutyloxy)-benozates have been prepared. The compounds are nematogenic; in addition the first three members exhibit a smectic A phase. The nematic-isotropic transition temperatures decrease with little or no alternation on increasing the number of methylene groups in the lateral chain; this is analogous to the behaviour found in monomeric and polymeric mesogens possessing lateral alkyl chains.     

Fragmentation reactions of deprotonated peptides containing proline. The proline effect

The collision-induced dissociation (CID) fragmentation reactions of a variety of deprotonated peptides containing proline have been studied in detail using MS(2) and MS(3) experiments, deuterium labelling and accurate mass measurements when necessary. The [M--H--CO(2)](-) (a(2)) ion derived from H-Pro-Xxx-OH dipeptides shows an unusual fragmentation involving loss of C(2)H(4); this fragmentation reaction is not observed for larger peptides. The primary fragmentation reactions of deprotonated tripeptides with an N-terminal proline are formation of a(3) and y(1) ions. When proline is in the central position of tripeptides, a(3), y(2) and y(1) ions are the primary fragmentation products of [M--H](-), while when the proline is in the C-terminal position, a(3)and y(1) ions are the major primary products. In the latter case, the a(3) ion fragments primarily to the 'b(2) ion; further evidence is presented that the 'b(2) ions have a deprotonated oxazolone structure. Larger deprotonated peptides having at least two amino acid residues N-terminal to proline show a distinct preference for cleavage of the amide bond N-terminal to proline to form, mainly, the appropriate y ion. This proline effect is compared and contrasted with the similar proline effect observed in the fragmentation of protonated peptides containing proline.     

Gas-phase fragmentation of deprotonated p-hydroxyphenacyl derivatives

Electrospray ionization of methanolic solutions of p-hydroxyphenacyl derivatives HO-C(6)H(4)-C(O)-CH(2)-X (X = leaving group) provides abundant signals for the deprotonated species which are assigned to the corresponding phenolate anions (-)O-C(6)H(4)-C(O)-CH(2)-X. Upon collisional activation in the gas phase, these anions inter alia undergo loss of a neutral "C(8)H(6)O(2)" species concomitant with formation of the corresponding anions X(-). The energies required for the loss of the neutral roughly correlate with the gas phase acidities of the conjugate acids (HX). Extensive theoretical studies performed for X = CF(3)COO in order to reveal the energetically most favorable pathway for the formation of neutral "C(8)H(6)O(2)" suggest three different routes of similar energy demands, involving a spirocyclopropanone, epoxide formation, and a diradical, respectively.     

Mesogenic aromatic esters with sulphur containing alkyl chains

A new series of aromatic esters, 1 and 2 with a sulphur atom in one of the side chains, is described. They exhibit nematic and/or smectic A/C mesophases as a function of the length of the alkyloxy chain. The presence of sulphur in the 4-position of the alkanoyloxy chain depresses both the clearing and the melting points with respect to the corresponding carbon analogues 3, resulting from the higher conformational mobility of the thiaalkyl chain. In 2, the presence of a methyl group in the 2-position of the alkanoyloxy chain induces a S_A phase below room temperature.     

Rubbing-induced anisotropy of long alkyl side chains at polyimide surfaces

Molecular organization at polyimide surfaces used as alignment layers in liquid crystal displays was investigated using vibrational sum frequency generation (SFG) spectroscopy. We focus on the orientation of the long alkyl side groups at the polymer surface using polarization-selected SFG spectra of the CH(3)- and CH(2)-stretch modes of the side chain. Mechanical rubbing and baking, an accepted industrial procedure used to produce pretilt of the liquid crystal, was found to induce pronounced azimuthal anisotropy in the orientational distribution of the alkyl side chains. Orientational analysis of the SFG vibrational spectra in terms of the azimuthal and tilt angles (in and out of plane, respectively) of the alkyl side chains shows their preferential tilt along the rubbing direction, with the azimuthal distribution narrower for stronger rubbed polymer samples.     

Synthesis of comb-like polyurethanes containing hydrophilic phosphatidylcholine analogues in the main chains and hydrophobic long chain alkyl groups in the side chains

Three new amphiphilic phospholipid diols containing hydrophilic phosphatidylcholine analogues in the main chains and hydrophobic octadecyl, hexadecyl or dodecyl alkyl groups in the side chains were synthesized. The typical phospholipid diol based on an octadecyl group was further reacted with diisocyanates such as hexamethylene diisocyanate (HDI), 2,4-tolylene diisocyanate (TDI) and 4,4′-methylenediphenyl diisocyanate (MDI), respectively. Preliminary studies suggest that polyurethane based on MDI shows a viscosity behavior similar to common polyelectrolytes and exhibits a therm decomposition peak at 244°C due to the phospholipid moiety and a melting point at 218°C.     

Aib-rich peptides containing lactam-bridged side chains as models of the 3(10)-helix.

Aib-rich side chain lactam-bridged oligomers with n =1, 2, 3, were designed and synthesized as putative models of the 3(10)-helix. These peptides were conformationally characterized in aqueous solution containing SDS micelles by CD, NMR, and computer simulations. The lactam bridge between the side chains of L-Glu and L-Lys in (i) and (i+3) positions was introduced in order to enhance the conformational preference toward the right-handed 3(10)-helix. The NMR results clearly indicate that there is an increase of 3(10)-helix formation upon chain elongation. In the dimer and trimer (n = 2 and n = 3, respectively, in the structure reported above) the observed NOE connectivities are compatible with the 3(10)-helical arrangement, confirmed by the temperature coefficients of the amide proton resonances which suggest the presence of a hydrogen-bonded structure. The phi and psi dihedral angles of the structures obtained by molecular dynamics calculations are also compatible with the 3(10)-helix. Identification of the hydrogen-bond pattern indicate that C=O(i)- - -HN(i+3) hydrogen bonds, typical of the 3(10)-helical conformation, are highly probable in all low-energy structures. The CD spectra of these Aib-rich lactam-bridged oligopeptides, obtained in the same solvent system used for NMR experiments, provide important insight into the spectroscopic characteristics of the 3(10)-helix.     

Mechanisms for the selective gas-phase fragmentation reactions of methionine side chain fixed charge sulfonium ion containing peptides

To enable the development of improved tandem mass spectrometry based methods for selective proteome analysis, the mechanisms, product ion structures, and other factors influencing the gas-phase fragmentation reactions of methionine side-chain derivatized "fixed-charge" phenacylsulfonium ion containing peptide ions have been examined. Dissociation of these peptide ions results in the exclusive characteristic loss of the derivatized side chain, thereby enabling their selective identification. The resultant product ion(s) are then subjected to further dissociation to obtain sequence information for subsequent protein identification. Molecular orbital calculations (at the B3LYP/6-31 + G (d,p) level of theory) performed on a simple peptide model, together with experimental evidence obtained by multistage dissociation of a regioselectively deuterated methionine derivatized sulfonium ion containing tryptic peptide, indicate that fragmentation of the fixed charge containing peptide ions occurs via SN2 reactions involving the N- and C-terminal amide bonds adjacent to the methionine side chain, resulting in the formation of stable cyclic five- and six-membered iminohydrofuran and oxazine product ions, respectively. These studies further indicate that the rings formed via these neighboring group reactions are stable to further dissociation by MS3. As a consequence, the formation of b- or y-type sequence ions are "skipped" at the site of cyclization. Despite this, complete sequence information is still obtained because of the presence of both cyclic products.     

Thermal studies on polythiophene containing mesogenic side chains

Series of thiophenes containing mesogenic side chains at the 3^rd position are synthesized. The thermal transitions and thermal stability of the synthesized monomers and polymers are studied. The polarizing microscopic studies of synthesized monomers showed nematic liquid crystalline phase and these mesophases further confirmed by differential scanning calorimetric study. The obtained melting and the isotropic temperatures decrease linearly with the increase of aliphatic chain length. The transition temperatures determined from DSC analysis, overlap well with the temperatures obtained from optical microscopy studies. Thermal stability of the compounds is analysed using thermogravimetric studies. Thermal stability of monomers and polymers has been determined by calculating IPDT values. Structural influence on thermal degradation patterns of monomers and polymers are also discussed.     

Synthesis of new liquid crystalline compounds with side chains containing hydroxy groups or chlorine atom

Catalytic hydrogenation of the oxo group in 3-hydroxy-1-(4-hydroxyphenyl)octan-1-one gave 1-(4-hydroxyphenyl)octane-1,3-diol and 1-(4-hydroxyphenyl)octan-3-ol which were converted into the corre-sponding benzyl ethers containing a hydroxy group, 1,3-diol fragment, or chlorine atom in the side chain. The products were shown to possess liquid crystalline properties.     

Fine-tuning of polymer photovoltaic properties by the length of alkyl side chains

This paper reports the synthesis and characteristics of a series of alkyl-substituted planar polymers. The physical properties are carefully tuned to optimize their photovoltaic performance. Depending on the length of soluble alkyl side chains which modify the structural order and orientation substantially in polymer backbones, the device performance can be improved significantly. The tuning of HOMO energy levels optimized polymers’ spectral coverage of absorption and their hole mobility, as well as miscibility with fullerene; all these efforts enhanced polymer solar cell performances. The shortcircuit current, Jsc for polymer solar cells was increased by adjusting polymer chain packing ability. It was found that films with well distributed polymer/fullerene interpenetrating network exhibit improved solar cell conversion efficiency. Enhanced efficiency up to 5.8% has been demonstrated. The results provide important insights about the roles of flexile chains in structure-property relationship for the design of new polymers to be used in high efficient solar cells.     

Postsynthetic modification of peptides via chemoselective N-alkylation of their side chains

A chemoselective, mild, and versatile method for performing postsynthetic modifications of peptide sequences is described. It requires only activated molecular sieves in the presence of an alkyl halide in order to N-alkylate lysine side chains. This reaction is fully compatible with most of the peptide functionalities, discriminates the reactivity of differently protected lysines, and proceeds in good yield. The mild conditions employed were further proved by performing the N-alkylation of a peptide containing a disulfide bridge.     

Photoinduced conformational changes of azoaromatic polyaspartates containing octadecyl side chains

Copolymers of p-(phenylazo)benzyl-L-aspartate and n-octadecyl-L-aspartate exist as right- and left-handed α-helices in solution at 25°C depending on the copolymer composition: the reversal of helix sense from a right- to left-handed one occurs with increasing the azobenzene content. The α-helices of the copolymers are very sensitive to trifluoroacetic acid (TFA), and are converted into random coil below 2.0% of TFA. Among the copolymers, the copolymer containing 47% azobenzene groups is unique since it exhibits a TFA-induced conformational change from right-handed α-helix to random coil via left-handed α-helix. Upon UV light irradiation at 25°C, the copolymers containing 68 and 89% azobenzene groups caused the reversal in helix sense from a left- to right-handed one. The conformations of the copolymers were dependent on temperature, mostly right-handed and left-handed α-helices at lower and higher temperatures, respectively. On this basis, the copolymer containing 47% azobenzene groups could be made to undergo a photoinduced helix reversal at high temperatures.