Oligomeric Building Blocks Research Articles

Direct C–H Arylation-Derived Oligomeric Building Blocks Incorporated into Conjugated Polymers for Organic Solar Cell Applications

Direct C–H Arylation-Derived Oligomeric Building Blocks Incorporated into Conjugated Polymers for Organic Solar Cell Applications

Composition-controlled degradation behavior of macroporous scaffolds from three-armed biodegradable macromers

Acidification of implant microenvironment and inflammation due to degradation products of high molecular weight poly(α‑hydroxy acids) like PLA and PLGA is a risk that can limit their use in regenerative medicine, tissue engineering and drug delivery. We developed macromers that consist of a three-armed core with varying degrees of ethoxylation, hydrolytically degradable oligolactide blocks and terminal methacrylate groups (TriLA macromers) for cross-polymerization into monolithic or macroporous structures. Within the macromer platform, biophysical and biochemical properties can be adjusted by macromer chemistry. In this work, eight new macromer types with a reduced degree of methacrylation or substitution of a fraction of the lactic acid units with glycolic acid were successfully synthesized starting from a fully methacrylated, oligolactide-based TriLA macromer. Chemical characterization confirmed feed-dependent glycolic acid integration and controlled reduction in degree of methacrylation. The degradation behavior of macroporous scaffolds made by solid lipid templating from both the previously established and the new macromers was systematically investigated. In general, the scaffolds displayed continuous mass loss over time when the onset time of degradation was passed. Depending on arm length as well as hydrophilicity of the oligomeric building blocks, degradation half-life ranged from 3 to 4 weeks to over 81 weeks. Glycolic acid integration accelerated network degradation more effectively than an increase in core molecule hydrophilicity. The observed, adjustable degradation profiles with only moderate medium acidification and a dominant phase of almost linear mass loss make this material platform promising for regenerative and drug delivery applications.

Design of multi-scale protein complexes by hierarchical building block fusion

A systematic and robust approach to generating complex protein nanomaterials would have broad utility. We develop a hierarchical approach to designing multi-component protein assemblies from two classes of modular building blocks: designed helical repeat proteins (DHRs) and helical bundle oligomers (HBs). We first rigidly fuse DHRs to HBs to generate a large library of oligomeric building blocks. We then generate assemblies with cyclic, dihedral, and point group symmetries from these building blocks using architecture guided rigid helical fusion with new software named WORMS. X-ray crystallography and cryo-electron microscopy characterization show that the hierarchical design approach can accurately generate a wide range of assemblies, including a 43 nm diameter icosahedral nanocage. The computational methods and building block sets described here provide a very general route to de novo designed protein nanomaterials.

Microbial Production of Biodegradable Lactate-Based Polymers and Oligomeric Building Blocks From Renewable and Waste Resources.

Polyhydroxyalkanoates (PHAs) are naturally occurring biopolymers produced by microorganisms. PHAs have become attractive research biomaterials in the past few decades owing to their extensive potential industrial applications, especially as sustainable alternatives to the fossil fuel feedstock-derived products such as plastics. Among the biopolymers are the bioplastics and oligomers produced from the fermentation of renewable plant biomass. Bioplastics are intracellularly accumulated by microorganisms as carbon and energy reserves. The bioplastics, however, can also be produced through a biochemistry process that combines fermentative secretory production of monomers and/or oligomers and chemical synthesis to generate a repertoire of biopolymers. PHAs are particularly biodegradable and biocompatible, making them a part of today’s commercial polymer industry. Their physicochemical properties that are similar to those of petrochemical-based plastics render them potential renewable plastic replacements. The design of efficient tractable processes using renewable biomass holds key to enhance their usage and adoption. In 2008, a lactate-polymerizing enzyme was developed to create new category of polyester, lactic acid (LA)–based polymer and related polymers. This review aims to introduce different strategies including metabolic and enzyme engineering to produce LA-based biopolymers and related oligomers that can act as precursors for catalytic synthesis of polylactic acid. As the cost of PHA production is prohibitive, the review emphasizes attempts to use the inexpensive plant biomass as substrates for LA-based polymer and oligomer production. Future prospects and challenges in LA-based polymer and oligomer production are also highlighted.

Biodegradable Polymeric Materials in Degradable Electronic Devices.

Biodegradable electronics have great potential to reduce the environmental footprint of devices and enable advanced health monitoring and therapeutic technologies. Complex biodegradable electronics require biodegradable substrates, insulators, conductors, and semiconductors, all of which comprise the fundamental building blocks of devices. This review will survey recent trends in the strategies used to fabricate biodegradable forms of each of these components. Polymers that can disintegrate without full chemical breakdown (type I), as well as those that can be recycled into monomeric and oligomeric building blocks (type II), will be discussed. Type I degradation is typically achieved with engineering and material science based strategies, whereas type II degradation often requires deliberate synthetic approaches. Notably, unconventional degradable linkages capable of maintaining long-range conjugation have been relatively unexplored, yet may enable fully biodegradable conductors and semiconductors with uncompromised electrical properties. While substantial progress has been made in developing degradable device components, the electrical and mechanical properties of these materials must be improved before fully degradable complex electronics can be realized.

Biodegradable and adjustable sol-gel glass based hybrid scaffolds from multi-armed oligomeric building blocks.

Adaption of degradation kinetics toward physiological relevance is still an unmet challenge of (bio-)glass engineering. We therefore present a glass-derived hybrid material with adjustable degradation. A flexible design concept based on degradable multi-armed oligomers was combined with an established indirect rapid prototyping method to produce a systematic set of porous sol-gel-derived class II hybrid scaffolds. Mechanical properties in the range of cancellous bone were narrowly controlled by hybrid composition. The oligoester introduction resulted in significantly increased compressive moduli. Cytocompatible hybrids degraded in physiologically relevant time frames and a promising linear and controllable weight loss profile was found. To our knowledge, our degradation study represents the most extensive long-term investigation of sol-gel-derived class II hybrids. Due to the broad adjustability of material properties, our concept offers potential for engineering of biodegradable hybrid materials for versatile applications.

Hydration effects on the electronic properties of eumelanin building blocks.

Theoretical results for the electronic properties of eumelanin building blocks in the gas phase and water are presented. The building blocks presently investigated include the monomeric species DHI (5,6-dihydroxyindole) or hydroquinone (HQ), DHICA (5,6-dihydroxyindole-2-carboxylic acid), indolequinone (IQ), quinone methide (MQ), two covalently bonded dimers [HM ≡ HQ + MQ and IM ≡ IQ + MQ], and two tetramers [HMIM ≡ HQ + IM, IMIM ≡ IM + IM]. The electronic properties in water were determined by carrying out sequential Monte Carlo/time dependent density functional theory calculations. The results illustrate the role played by hydrogen bonding and electrostatic interactions in the electronic properties of eumelanin building blocks in a polar environment. In water, the dipole moments of monomeric species are significantly increased ([54-79]%) relative to their gas phase values. Recently, it has been proposed that the observed enhancement of the higher-energy absorption intensity in eumelanin can be explained by excitonic coupling among eumelanin protomolecules [C.-T. Chen et al., Nat. Commun. 5, 3859 (2014)]. Here, we are providing evidence that for DHICA, IQ, and HMIM, the electronic absorption toward the higher-energy end of the spectrum ([180-220] nm) is enhanced by long-range Coulombic interactions with the water environment. It was verified that by superposing the absorption spectra of different eumelanin building blocks corresponding to the monomers, dimers, and tetramers in liquid water, the behaviour of the experimental spectrum, which is characterised by a nearly monotonic decay from the ultraviolet to the infrared, is qualitatively reproduced. This result is in keeping with a "chemical disorder model," where the broadband absorption of eumelanin pigments is determined by the superposition of the spectra associated with the monomeric and oligomeric building blocks.

Synthesis and Photophysical Properties of New α,Ω-Bis(Tpy)Oligothiophenes and Their Metallo-Supramolecular Polymers With Zn2+ Ion Couplers

Five new α,ω-bis(tpy)bithiophenes and terthiophenes, each comprising two hexyl groups attached to oligothiophene block at different positions, were prepared using the Suzuki coupling strategy, characterized (NMR, IR, Raman, HRMS, UV/vis, fluorescence, cyclic voltammetry) and transformed to corresponding conjugated metallo-supramolecular polymers with Zn2+ ion-couplers. Reference oligomers with unsubstituted central blocks and their polymers are also reported. Photophysical properties of oligomers and polymers are described, analyzed with a help of DFT calculations, and correlated with the chemical constitution of oligomeric building blocks. Steric effects were shown to exceed the electronic effects of hexyl groups, and twisting the thiophene-thiophene bonds were shown to influence electronic spectra of oligomers and polymer more deeply than twisting the thiophene-tpy bonds. Outlying photoluminescence characteristics observed for some oligomers and polymers were shown to be consistent with the other data based on their analysis by the Stokes shift approach. Polymers prepared exhibited good constitutional dynamics in DMSO but only limited dynamics in THF solutions. IR and Raman spectra allowing identification of solid oligomers and polymers are also presented.

Sialo-CEST: chemical exchange saturation transfer NMR of oligo- and poly-sialic acids and the assignment of their hydroxyl groups using selective- and HSQC-TOCSY

Chemical exchange saturation transfer (CEST) is an NMR method that takes advantage of proton exchange between solute and solvent molecules in dynamic equilibrium, enabling the detection of the solute NMR signals with enhanced sensitivity. Herein, we report that the hydroxyl groups in a naturally occurring polysaccharide, α-2,8 polysialic acid in aqueous solution, yield very significant CEST effects even at 37°C where the resonances of the hydroxyl groups are not directly observed. We also report the assignments of the hydroxyl groups for the polymer and its oligomeric building blocks, from monomer to hexamer. We show that the same assignments can be made by either 1H–1H TOCSY methods or 1H–13C HSQC-TOCSY methods, to alleviate spectral overlap. Finally, we report the exchange rates of the OH groups with water and show how these rates can be used to select and fine-tune CEST effects.

The Dynamics and Energetics of Matrix Assembly and Mineralization

Formation of biominerals commonly occurs within the context of an organic matrix composed of proteins, polysaccharides, and other macromolecules. Much has been learned about the structure of matrices and the spatial and molecular relationships between matrix and mineral. Only recently has quantitative study of matrix organization and subsequent mineralization been pursued. Here, we review findings from physical studies of matrix assembly in the system of microbial S-layer proteins and of calcium carbonate nucleation on organic templates composed of organothiol self-assembled monolayers on noble metals. Studies on S-layers reveal the importance of multistage assembly pathways and kinetic traps associated with the conformational transformations required to build the basic oligomeric building blocks of the matrix. Experimental investigations of calcium carbonate nucleation on carboxyl-terminated self-assembled monolayers combined with theoretical analyses demonstrate the applicability of classical concepts of nucleation, even when cluster-aggregation pathways are considered, and reveal the underlying energetic and structural source of matrix control over the process. Taken together, these studies highlight the ways in which matrix assembly and mineralization deviate from our classical concepts of crystallization but clearly demonstrate that the concepts of physical chemistry that date back to the days of Gibbs and Ostwald still serve us well in understanding the nucleation and growth of organic matrices and mineral phases.

Metastable micelles and true liquid crystal behaviour of newly designed “cataniomeric” surfactants

Jeffamines were used as molecular tools for the design of novel organized molecular systems based on so-called “cataniomeric” surfactants, which combine features of ionic liquids (ILs) and catanionic surfactants and which contain oligomeric building blocks. These systems show an original self-assembling behaviour in water, with a rich polymorphism: dynamic (or metastable) micelles and liquid crystals (cubic Im3m and Fm3m and hexagonal H1 phases). “Cataniomeric” surfactants were prepared by a simple acid–base reaction between oligomeric Jeffamine ED900 and various fatty acids (lauric, myristic, stearic and oleic acid) in a stoichiometric ratio, similar to well known salt-free catanionic surfactants. The phase behaviour was rationalized in terms of hydrocarbon chain length of the fatty counterion (equivalent carbon atoms, ECN) and of headgroup electrostatic interactions and flexibility. All synthesized surfactants show a direct micellar cubic phase, whose stability increases with hydrophobicity. A transition to a hexagonal phase takes place when ECN is higher than 29, and thus independently of the symmetry of the molecule. Thermal stability of the hexagonal phase also increases with ECN. An epitaxial transition of H1 → Im3m → Fm3m was also evidenced. These novel systems have straightforward applications in modern formulations or smart nanodevices, reversibly responsive to external stimuli.

Morphology-Controlled Synthesis of Nanocrystalline η-Al2O3 Thin Films, Powders, Microbeads, and Nanofibers with Tunable Pore Sizes from Preformed Oligomeric Oxo-Hydroxo Building Blocks

Herein the synthesis and characterization of nanocrystalline η-Al2O3 materials with different morphologies, including dense nanofibers, hierarchically porous microbeads, and highly ordered mesoporous thin films and powders is reported. These materials were fabricated by facile polymer templating, nanocasting, and electrospinning routes using preformed aluminum-oxo-hydroxo species as the building blocks. We show that the oligomeric building blocks used in this work can be formed under nonaqueous conditions with benzyl alcohol as the oxygen donor and further converted to the eta-phase of Al2O3 at temperatures above 700 °C. Electron microscopy, X-ray diffraction, grazing incidence small-angle X-ray scattering, X-ray photoelectron spectroscopy, and physisorption studies collectively verify that the different η-Al2O3 materials are well-defined at the nanoscale and the microscale after annealing in air at temperatures as high as 1000 °C. In addition, data obtained on polymer-templated thin films show that both cubic and 2D-hexagonal structures with large pore sizes between 10 and 30 nm can be achieved. These data also show that the conversion of the initially amorphous frameworks comes at little cost to the ordering of the pore-solid architectures. Overall, we believe that the synthesis parameters described here provide a blueprint for future nanomaterials.

Oxo‐Metalate Building Blocks: Conceptual Competitors for Tetravalent Carbon?

In honor of Prof. Michael T. Pope for over half a century of excellent contributions to polyoxometalate chemistry The versatility of chemistry based on tetravalent carbon is unparalleled. Small organic molecules are readily modifiable by traditional serial syntheses and/or combinatorial libraries, and systematically linked together by Nature; in the laboratory, polymeric structures ranging from biological macromolecules to functional solid-state materials can be generated. Meanwhile, molecular or oligomeric building blocks can be designed to self-assemble into supramolecular structures, including increasingly sophisticated “nano-reactors” [1, 2] that link molecular to nano-scale worlds. When combined with metal cations, organic linkers can generate (now predictable) metal-organic frameworks (MOFs) with large and controllable pore sizes. [3]

ChemInform Abstract: Oligomeric Building Block Approach to the Synthesis of Diastereomerically Pure Pentathymidine 3′,5′-Methanephosphonates.

[formula: see text] A method for a large-scale synthesis of stereodefined oligo(nucleoside 3',5'-methanephosphonates) has been developed, based on transient 3'-O protection, which allows for the conversion of the protecting chirally defined methanephosphonanilidate group, located at the 3' end of a stereoregular oligomer, into diastereomerically pure oligomeric building blocks for stereospecific coupling with the 5'-OH group of another oligonucleotide.

Identification of a subunit interface in transthyretin amyloid fibrils: evidence for self-assembly from oligomeric building blocks.

Amyloid and prion diseases appear to stem from the conversion of normally folded proteins into insoluble, fiber-like assemblies. Despite numerous structural studies, a detailed molecular characterization of amyloid fibrils remains elusive. In particular, models of amyloid fibrils proposed thus far have not adequately defined the constituent protein subunit interactions. To further our understanding of amyloid structure, we employed thiol-specific cross-linking and site-directed spin labeling to identify specific protein-protein associations in transthyretin (TTR) amyloid fibrils. We find that certain cysteine mutants of TTR, when dimerized by chemical cross-linkers, still form fibers under typical in vitro fibrillogenic conditions. In addition, site-directed spin labeling of many residues at the natural dimer interface reveals that their spatial proximity is preserved in the fibrillar state even in the absence of cross-linking constraints. Here, we present the first view of a subunit interface in TTR fibers and show that it is very similar to one of the natural dimeric interchain associations evident in the structure of soluble TTR. The results clarify varied models of amyloidogenesis by demonstrating that transthyretin amyloid fibrils may assemble from oligomeric protein building blocks rather than structurally rearranged monomers.

Oligomeric building block approach to the synthesis of diastereomerically pure pentathymidine 3',5'-methanephosphonates.

[formula: see text] A method for a large-scale synthesis of stereodefined oligo(nucleoside 3',5'-methanephosphonates) has been developed, based on transient 3'-O protection, which allows for the conversion of the protecting chirally defined methanephosphonanilidate group, located at the 3' end of a stereoregular oligomer, into diastereomerically pure "oligomeric building blocks" for stereospecific coupling with the 5'-OH group of another oligonucleotide.

Fast identification by FAB-mass spectrometry of building blocks for oligonucleotide synthesis

Negative ion FAB-MS is recommended for the rapid routine identification of monomeric as well as oligomeric building blocks used in the phosphotriester synthesis of DNA fragments.

Prebiotic organic matter: possible pathways for synthesis in a geological context

The variety of pathways for synthesis and chemical evolution of organic matter involved in the origins of life on the primitive Earth must have been constrained by the early geophysical-geochemical evolution of the planet that resulted from accretion and core formation. These processes would have strongly influenced the temperature and composition of the atmosphere, surface and interior over time. Yet large gaps persist in our understanding of how Earth accreted and differentiated into the core-mantle-crust-atmosphere system. Moreover, major uncertainties exist about the time-span over which Earth acquired its volatiles, the elemental abundances in its volatiles inventory, and the conditions under which outgassing of these volatiles occurred to form the primitive atmosphere. Within the context of existing models for Earth accretion and early evolution these uncertainties allow a wide range of possible prebiotic atmospheric compositions at the time and temperature when liquid water appeared and thermally-labile organic compounds could survive. These compositions range from strongly reducing, dominated by high abundances of H 2. CO and CH 4, to mildly reducing, containing mostly N 2 with minor to trace amounts of CO 2 and H 2. Laboratory experiments indicate that prebiotic synthesis of organic matter would have occurred readily in strongly reducing atmospheres. The possibilities in mildly or non-reducing atmospheres may have been more limited, but they merit much more study than they have received. The conversion of N 2 to nitrogen-containing organic compounds in any prebiotic atmosphere could have been difficult to achieve by atmospheric photochemical processes; electric discharges or other processes may have been more effective. Prebiotic organic syntheses need not have occurred only in the atmosphere; they could have occurred on land, in the seas, and at the interfaces between atmosphere, seas, and land surfaces. The involvement of inorganic matter in the origin of life is expected to have been a natural consequence of the geological context within which atmospheric and organic chemical evolution occurred. Metal ions and minerals, particularly clays, could have served as reactants, catalysts, and even templates for prebiotic organic synthesis. Thus far, considerable success has been achieved in producing the monomeric and oligomeric building blocks of present day proteins and nucleic acids in putative prebiotic syntheses. But the connections between the model environmental conditions implicit in many of the syntheses and the geologic and meteorologic realities of the prebiotic Earth may be tenuous and remain to be established clearly. Until tighter constraints can be imposed on the range of possible prebiotic atmospheric compositions and surface environments, and in the absence of direct evidence of terrestrial organic chemical evolution, it is important to explore and assess pathways for organic synthesis in all model environments that continue to be consistent with evidence unveiled in the cosmochemical, geological and biological records.