Mechanism of the Anionic Ring-Opening Oligomerization of Propylene Carbonate Initiated by the tert-Butylphenol/KHCO3 System

The ring-opening oligomerization reaction of propylene carbonate in the presence of the tert-butylphenol/KHCO₃ initiating system was studied by means of Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) and Electrospray Ionization Time of Flight Mass Spectrometry (ESI-TOF MS). According to the MS spectra obtained, different series of peaks were identified. The MS spectra clearly showed that besides the chain-extension reaction yielding oligomers with all propylene oxide units, the formation of oligomers containing carbonate linkages in the chain, and condensation reaction between the latter two also took place. The structure of the oligomers carrying carbonate linkages was determined by the post-source decay (PSD) MALDI-TOF MS/MS method. Based on the MS results, a mechanism for the oligomerization reaction is proposed.     

Polycondensation of butenediol: synthesis of telechelic 2-butene-1,4-diol oligomers

The catalytic condensation of cis-2-butene-1,4-diol with CpRu(MQA)(C(3)H(5)) (Cp = cyclopentadienyl, MQA = 4-methoxyquinoline-2-carboxylate) generates poly(2-butenediol), an unsaturated telechelic polyether diol with molecular weights between 400 and 4600 g/mol. This Ru(IV) allyl catalyst enchains 2-butene-1,4-diol primarily as the linear trans-2-butenyl ether (92%) along with vinyl branches (8%). These telechelic oligomers are useful chain extenders and macromonomers, as demonstrated by their use in the synthesis of poly(lactide)-b-poly(butenediol)-b-poly(lactide) triblock copolymers. Model studies support a proposed mechanism involving the formation of Ru(IV) allyl intermediates from allylic alcohols and chain growth by selective nucleophilic displacement at the terminus of the Ru(IV) allyl to generate trans-2-butenyl ether linkages.     

Laccase‐Catalyzed Synthesis of Low‐Molecular‐Weight Lignin‐Like Oligomers and their Application as UV‐Blocking Materials

The laccase‐catalyzed oxidative polymerization of monomeric and dimeric lignin model compounds was carried out with oxygen as the oxidant in aqueous medium. The oligomers were characterized by using gel permeation chromatography (GPC) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectroscopy (MALDI‐TOF MS) analysis. Oxidative polymerization led to the formation of oligomeric species with a number‐average molecular weight (M_n) that ranged from 700 to 2300 Da with a low polydispersity index. Spectroscopic analysis provided insight into the possible modes of linkages present in the oligomers, and the oligomerization is likely to proceed through the formation of C?C linkages between phenolic aromatic rings. The oligomers were found to show good UV light absorption characteristics with high molar extinction coefficient (5000–38 000 m ^?1 cm^?1) in the UV spectral region. The oligomers were blended independently with polyvinyl chloride (PVC) by using solution blending to evaluate the compatibility and UV protection ability of the oligomers. The UV/Vis transmittance spectra of the oligomer‐embedded PVC films indicated that these lignin‐like oligomers possessed a notable ability to block UV light. In particular, oligomers obtained from vanillyl alcohol and the dimeric lignin model were found to show good photostability in accelerated UV weathering experiments. The UV‐blocking characteristics and photostability were finally compared with the commercial low‐molecular‐weight UV stabilizer 2,4‐dihydroxybenzophenone.     

Long, directional interactions in cofacial silicon phthalocyanine oligomers

Single crystal structures have been determined for the three cofacial, oxygen-bridged, silicon phthalocyanine oligomers, [((CH(3))(3)SiO)(2)(CH(3))SiO](SiPcO)(2-4)[Si(CH(3))(OSi(CH(3))(3))(2)], and for the corresponding monomer. The data for the oligomers give structural parameters for a matching set of three cofacial, oxygen-bridged silicon phthalocyanine oligomers for the first time. The staggering angles between the six adjacent cofacial ring pairs in the three oligomers are not in a random distribution nor in a cluster at the intuitively expected angle of 45° but rather are in two clusters, one at an angle of 15° and the other at an angle of 41°. These two clusters lead to the conclusion that long, directional interactions (LDI) exist between the adjacent ring pairs. An understanding of these interactions is provided by atoms-in-molecules (AIM) and reduced-density-gradient (RDG) studies. A survey of the staggering angles in other single-atom-bridged, cofacial phthalocyanine oligomers provides further evidence for the existence of LDI between cofacial phthalocyanine ring pairs in single-atom-bridged phthalocyanine oligomers.     

Photophysics of pi-conjugated metal-organic oligomers: aryleneethynylenes that contain the (bpy)Re(CO)(3)Cl chromophore

A comprehensive study of a series of four monodisperse, metal-organic pi-conjugated oligomers of varying length is reported. The oligomers are based on the aryleneethynylene architecture, and they contain a 2,2'-bipyridine-5,5'-diyl (bpy) metal binding unit. The photophysical properties of the free oligomers and their complexes with the (L)Re(I)(CO)(3)X chromophore (where L = the bpy-oligomer and X = Cl or NCCH(3)) were explored by a variety of methods including electrochemistry, UV-visible absorption, variable temperature photoluminescence (PL), transient absorption (TA), and time-resolved electron paramagnetic spectroscopy (TREPR). The absorption of the free oligomers and the metal complexes is dominated by the pi,pi* transitions of the pi-conjugated oligomers. The free oligomers feature a strong blue fluorescence that is quenched entirely in the (L)Re(I)(CO)(3)X complexes. The metal-oligomers feature a weak, relatively long-lived red photoluminescence that is assigned to emission from both the (3)pi,pi* manifold of the pi-conjugated system and the dpi Re --> pi* bpy-oligomer metal-to-ligand charge transfer ((3)MLCT) state. On the basis of a detailed analysis of the PL, TA, and TREPR results an excited-state model is developed which indicates that the oligomer-based (3)pi,pi* state and the (3)MLCT states are in close energetic proximity. Consequently the photophysical properties reflect a composite of the properties of the two excited-state manifolds.     

SYNTHESIS, CHARACTERIZATION AND RING-OPENING POLYMERIZATION OF CYCLIC (ARYLENE PHOSPHONATE) OLIGOMERS

INTRODUCTIONThe use of cyclic oligomers as macrocyclic precursors for the preparation of high performance polymers byring-opening polymerization (ROP) has sparked much interest in recent years. It could produce a revolutionarychange in the preparation of advanced composite materials, and is of great importance in the polymerizationprocess yielding polymers such as the reinforced reactive injection model (RRIM) and the resin transfer model(RTM) etc. Within the last 10 years, the synthes…     

Analysis of disulphide linkages in bovine kappa-casein oligomers using two-dimensional electrophoresis

Disulphide bonds play an important role in protein structure and function. Bovine kappa-casein (kappa-csn), an important glycoprotein in milk, contains two cysteines that can form disulphide bonds. On 2-D gels run under nonreducing conditions the kappa-csn in milk presented a complex pattern of monomers and disulphide-linked oligomers. Trains of spots corresponding to monomers to hexamers were observed as a result of the participation of different glycoforms and phosphoforms in oligomer formation. The dimers and trimers ran as doublets on the gel and analysis of the disulphide-linked peptides released from them after in-gel tryptic digestion showed they were the result of different disulphide linkages. The linkages were confirmed by MSMS. When milks with electrophoretically distinct genetic variants of kappa-csn were mixed and run on 2-D gels, they retained their distinct patterns indicating that disulphide exchange reactions or disulphide 'scrambling' was not occurring during 2-D analysis. The patterns observed represent the native distribution of kappa-csn in milk at harvest. The role and significance of the disulphide bonding of kappa-csn are discussed.     

Mechanism for radical cation transport in duplex DNA oligonucleotides

We investigated the photoinduced one-electron oxidation of a series of DNA oligomers having a covalently linked anthraquinone group (AQ) and containing [(A)(n)GG](m) or [(T)(n)GG](m) segments. These oligomers have m GG steps, where m = 4 or 6, separated by (A)(n) or (T)(n) segments, where n = 1-7 for the (A)(n) set and 1-5 for the (T)(n) set. Irradiation with UV light that is absorbed by the AQ causes injection of a radical cation into the DNA. The radical cation migrates through the DNA, causing chemical reaction, primarily at GG steps, that leads to strand cleavage after piperidine treatment. The uniform, systematic structure of the DNA oligonucleotides investigated permits the numerical solution of a kinetic scheme that models these reactions. This analysis yields two rate constants, k(hop), for hopping of the radical cation from one site to adjacent sites, and k(trap), for irreversible reaction of the radical cation with H(2)O or O(2). Analysis of these findings indicates that radical cation hopping in these duplex DNA oligomers is a process that occurs on a microsecond time scale. The value of k(hop) depends on the number of base pairs in the (A)(n) and (T)(n) segments in a systematic way. We interpret these results in terms of a thermally activated adiabatic mechanism for radical cation hopping that we identify as phonon-assisted polaron hopping.     

Copolymerization of elemental sulfur with cyclic(arylene disulfide) oligomers

Copolymerization reactions between cyclic(arylene disulfide) oligomers were studied. The cyclic disulfide oligomers derived from 4,4′-isopropylidene bisbenzenethiol gave soluble polysulfanes via copolymerization with S₈. The copolymerization reactions were studied both in solution and melt by GPC and NMR. Solution copolymerization reactions can only form polysulfanes with up to three to four sulfur linkages; however, melt copolymerization reactions gave polysulfanes with up to seven sulfur linkages (average). The melt copolymerization reactions between cyclic disulfide oligomers derived from 4,4′-thiobis(benzenethiol) and S₈ were studied using DSC, TGA, and DMTA. With increasing contents of sulfur in the polysulfanes, T_gs, 5% weight losses by TGA, and tan δ decreased. With seven sulfur linkages in the polymer, it is a rubber with a T_g of 12°C, a 5% weight loss by TGA of 249°C, and tan δ of 44°C, respectively. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2961–2968, 1997     

Ester‐Mediated Amide Bond Formation Driven by Wet–Dry Cycles: A Possible Path to Polypeptides on the Prebiotic Earth

Although it is generally accepted that amino acids were present on the prebiotic Earth, the mechanism by which α‐amino acids were condensed into polypeptides before the emergence of enzymes remains unsolved. Here, we demonstrate a prebiotically plausible mechanism for peptide (amide) bond formation that is enabled by α‐hydroxy acids, which were likely present along with amino acids on the early Earth. Together, α‐hydroxy acids and α‐amino acids form depsipeptides—oligomers with a combination of ester and amide linkages—in model prebiotic reactions that are driven by wet–cool/dry–hot cycles. Through a combination of ester–amide bond exchange and ester bond hydrolysis, depsipeptides are enriched with amino acids over time. These results support a long‐standing hypothesis that peptides might have arisen from ester‐based precursors.     

Reliability of protonation constants of SNAZOXS oligomers

Concentration protonation constants of variously protonated of oligomers of sulphoazoxine SNAZOXS were determined by regression analysis of potentiometric titration curves. The group and common parameters were estimated using different computational strategies of three regression programs, MINIQUAD, MIQUV and PSEQUAD. ANOVA proved that six various computational strategies of three regression programs have no significant influence on reliability of protonation constants estimated in comparison with the reproducibility of the titration. Chemical model of protonation equilibria L(2)H(5-), L(2)H(4-)(2), L(2)H(3-)(3), and L(2)H(2-)(4) and reaction scheme of oligomers protonation for SNAZOXS was found.     

Preparation and structures of aryloxy- and alkoxy-Ti(IV) complexes and their evaluation in ethylene oligomerisation and polymerisation

A range of aryloxy and alkoxy ligands, both monodenate and chelating, have been coordinated to Ti(IV) to yield complexes of the form [Ti(OAr)(2)Cl(2)], [Ti(RO^O)Cl(3)] and [Ti(RO^O)(2)Cl(2)] (R = aryl, alkyl). The complexes vary in their Lewis base solvation and/or aggregation state, as revealed by X-ray crystallography of selected examples. The complexes have been evaluated as catalysts for ethylene oligomerisation and polymerisation following activation with alkylaluminium reagents (AlEt(3), methylaluminoxane). While polyethylene is the major product, ethylene oligomers also result, ranging from dimers to higher oligomers. The results indicate a number of different active species are formed upon activation, with oligomers likely arising through a metallacyclic mechanism. The findings are discussed in the context of the commercial Alphabutol dimerisation system [Ti(OR)(4)], and the development of group 4 based ethylene trimerisation catalysts.     

PROPOSED STRUCTURE OF THE TUMOR-LOCALIZING FRACTION OF HPD (HEMATOPORPHYRIN DERIVATIVE)

Abstract— Synthesis of the tumor-localizing preparation HPD (hematoporphyrin derivative) results in the formation of dimers and oligomers of hematoporphyrin joined by labile linkages. Studies with HPD and an HPD analog containing the chlorin analog of mesoporphyrin suggest the presence of two different linkages, either of which yields a tumor-localizing product. One such linkage is apparently derived from a hematoporphyrin-based oligomer present in commercial preparations of hematoporphyrin as an impurity. The other linkage is formed during the chemical steps leading to the conversion of hematoporphyrin to "HPD".     

Solid phase synthesis of peptidotriazoles with multiple cycles of triazole formation

Peptidotriazoles, unnatural oligomers with alternating amide and triazole linkages, are synthesized efficiently on solid support. The key transformations involve multiple cycles of 1,2,3-triazole formation, using soluble Cu(I) catalyst and conditions that do not generate precipitate on solid support nor require exclusion of oxygen. Our synthetic protocol will enable the preparation of other unnatural oligomers with multiple triazoles using solid phase methodologies.     

Synthesis and thermal properties of bisphthalonitriles containing aromatic ether nitrile linkages

Low-melting bisphthalonitrile oligomers with variable length of aromatic ether nitrile linkages (nPEN-BAPh) was firstly synthesized and the length of the linkages (n) was controlled by mole ratio of 2, 6-dichlorobenzonitrile and bisphenol A. The oligomers were characterized by FTIR and NMR spectra, and detailed study showed that the linkages were constructed in the backbone of nPEN-BAPh. The FTIR showed, with the curing reaction progressed, the characteristic peak of nitrile at 2230 cm⁻¹ disappeared while the characteristic peak of phthalocyanine ring at 3290, 1010 cm⁻¹ and triazine ring at 1360 cm⁻¹ appeared. The melting and polymerization temperature of the oligomers was around 60 °C and 220 °C, respectively. So a large processing window was obtained. The char yields of completely cured materials were above 65% at 800 °C in nitrogen and over 70% at 600 °C in air. All materials exhibited excellent thermal and thermo-oxidative stability.     

Oxazolidin-2-one-containing pseudopeptides that fold into beta-bend ribbon spirals

Three sets of oligomers containing the 4-carboxy-5-methyloxazolidin-2-one (Oxd) moiety have been synthesized with the aim of checking whether these molecules are able to fold in ordered structures: A set [Boc-(L-Ala-L-Oxd)(n)-OR], B set [Boc-(L-Ala-D-Oxd)(n)-OR], and C set [Boc-(Aib-L-Oxd)(n)-OR] preferential conformations have been analyzed with IR absorption, NMR, and CD. We have noticed that in these oligomers three stabilizing effects are active: (i) the rigid Oxd -CO-N(CH<)-CO- moiety, which always tend to assume a trans conformation; (ii) the formation of Oxd C=O...H-(alpha)C intramolecolar H-bonds; (iii) the alternate formation of 1 <-- 4 intramolecular C=O...H-N H-bonds. Through the analysis of the experimental data, we could demonstrate that only the oligomers of the B set are able to meet all three requirements listed above. By a deeper insight into the CD spectra, we gathered that the secondary structure adopted by the B set oligomers is a beta-bend ribbon spiral, which is a subtype of the 3(10)-helix.     

Application and Structural Analysis of Triazole-Bridged Disulfide Mimetics in Cyclic Peptides

Ruthenium-catalysed azide–alkyne cycloaddition (RuAAC) provides access to 1,5-disubstituted 1,2,3-triazole motifs in peptide engineering applications. However, investigation of this motif as a disulfide mimetic in cyclic peptides has been limited, and the structural consequences remain to be studied. We report synthetic strategies to install various triazole linkages into cyclic peptides through backbone cyclisation and RuAAC cross-linking reactions. These linkages were evaluated in four serine protease inhibitors based on sunflower trypsin inhibitor-1. NMR and X-ray crystallography revealed exceptional consensus of bridging distance and backbone conformations (RMSD<0.5 Å) of the triazole linkages compared to the parent disulfide molecules. The triazole-bridged peptides also displayed superior half-lives in liver S9 stability assays compared to disulfide-bridged peptides. This work establishes a foundation for the application of 1,5-disubstituted 1,2,3-triazoles as disulfide mimetics.     

Design of peptides that form amyloid-like fibrils capturing amyloid beta1-42 peptides

Amyloid beta-peptide (Abeta) plays a critical role in Alzheimer's disease (AD). The monomeric state of Abeta can self-assemble into oligomers, protofibrils, and amyloid fibrils. Since the fibrils and soluble oligomers are believed to be responsible for AD, the construction of molecules capable of capturing these species could prove valuable as a means of detecting these potentially toxic species and of providing information pertinent for designing drugs effective against AD. To this aim, we have designed short peptides with various hydrophobicities based on the sequence of Abeta14-23, which is a critical region for amyloid fibril formation. The binding of the designed peptides to Abeta and the amplification of the formation of peptide amyloid-like fibrils coassembled with Abeta are elucidated. A fluorescence assay utilizing thioflavin T, known to bind specifically to amyloid fibrils, revealed that two designed peptides (LF and VF, with the leucine and valine residues, respectively, in the hydrophobic core region) could form amyloid-like fibrils effectively by using mature Abeta1-42 fibrils as nuclei. Peptide LF also coassembled with soluble Abeta oligomers into peptide fibrils. Various analyses, including immunostaining with gold nanoparticles, enzyme-linked immunosorbent assays, and size-exclusion chromatography, confirmed that the LF and VF peptides formed amyloid-like fibrils by capturing and incorporating Abeta1-42 aggregates into their peptide fibrils. In this system, small amounts of mature Abeta1-42 fibrils or soluble oligomers could be transformed into peptide fibrils and detected by amplifying the amyloid-like fibrils with the designed peptides.     

Free solution mobility of small single-stranded oligonucleotides with variable charge densities

The free solution mobilities of six single-stranded 16-nucleotide DNA oligomers with the same sequence, containing up to 11 neutral phosphoramidate internucleoside linkages, have been measured by capillary electrophoresis. The mobilities of the partially charged oligomers increase linearly with the logarithm of increasing charge density, as predicted by the Manning theory of electrophoresis (G. S. Manning, J. Phys. Chem. 1981, 85, 1506-1515). For comparison, the mobilities of eight fully charged single-stranded oligomers containing similar numbers of charged phosphate residues have also been measured. The mobilities of the variable length, fully charged oligomers increase more rapidly with the increasing number of charged phosphate residues than the mobilities of the constant size, partially charged phosphoramidate derivatives, because of the larger diffusion coefficients of the modified oligomers.     

Monitoring oligomer formation from self-aggregating amylin peptides using ESI-IMS-MS

Amyloid diseases are a serious cause for concern world-wide. To understand the mechanism of formation of the fibrillar structures associated with such disorders, it is necessary to study the progression from soluble protein or peptide monomer through an array of oligomers to the final, insoluble, fibrils. The protein IAPP is found in vivo in the form of insoluble amyloid deposits in the pancreatic islets of diabetes type II sufferers. Here, we have studied the in vitro self-aggregation of three fibril-forming peptides from the amyloidogenic core of IAPP. Using electrospray ionization—mass spectrometry coupled with ion mobility spectrometry, the mass and cross-sectional area of each oligomer present in the heterogeneous assembly mixtures can be determined individually in a single, rapid experiment over time. For the three peptides studied, oligomers ≤20-mer were characterized. Conversely, no oligomers higher than a dimer were detected for a non-assembling peptide control. The rate in which the cross-sectional area of the oligomers increases with increasing number of peptide sub-units indicates that assembly for the amyloid-forming peptides proceeds in a linear fashion until an oligomer of a certain size is attained. After this, a step increase in cross-sectional area occurs for the next higher-order oligomer. This behaviour can be explained by molecular modelling of singly, doubly, triply and quadruply stacked β-stranded structures. Using one peptide as an example, the cross-sectional areas of the lower order oligomers (dimer to pentamer) were found to be consistent with a single β-sheet model, whereas the higher order oligomers were consistent with double-stranded (hexamer to decamer oligomers), triply-stranded (11-mers to 15-mers) and quadruply-stranded (16-mers to 20-mers) β-sheet models.