Monotelechelic Poly(oxa)norbornenes by Ring-Opening Metathesis Polymerization Using Direct End-Capping and Cross-Metathesis

Two different methodologies for the synthesis of monotelechelic poly(oxa)norbornenes prepared by living ring-opening metathesis polymerization (ROMP) are presented. The first method, termed direct end-capping, is carried out by adding an internal cis-olefin terminating agent (TA) to the reaction mixture immediately after the completion of the living ROMP reaction. The second method relies on cross-metathesis (CM) between a methylene-terminated poly(oxa)norbornene and a cis-olefin TA mediated by the ruthenium olefin metathesis catalyst (H_(2)IMes)(Cl)_(2)Ru(CH-o-OiPrC_(6)H_4) (H_(2)IMes = 1,3-dimesitylimidazolidine-2-ylidene). TAs containing various functional groups, including alcohols, acetates, bromides, α-bromoesters, thioacetates, N-hydroxysuccinimidyl esters, and Boc-amines, as well as fluorescein and biotin groups, were synthesized and tested. The direct end-capping method typically resulted in >90% end-functionalization efficiency, while the CM method was nearly as effective for TAs without polar functional groups or significant steric bulk. End-functionalization efficiency values were determined by ^(1)H NMR spectroscopy

End-functionalized glycopolymers as mimetics of chondroitin sulfate proteoglycans

Glycosaminoglycans are sulfated polysaccharides that play important roles in fundamental biological processes, such as cell division, viral invasion, cancer and neuroregeneration. The multivalent presentation of multiple glycosaminoglycan chains on proteoglycan scaffolds may profoundly influence their interactions with proteins and subsequent biological activity. However, the importance of this multivalent architecture remains largely unexplored, and few synthetic mimics exist for probing and manipulating glycosaminoglycan activity. Here, we describe a new class of end-functionalized ring-opening metathesis polymerization (ROMP) polymers that mimic the native-like, multivalent architecture found on chondroitin sulfate (CS) proteoglycans. We demonstrate that these glycopolymers can be readily integrated with microarray and surface plasmon resonance technology platforms, where they retain the ability to interact selectively with proteins. ROMP-based glycopolymers are part of a growing arsenal of chemical tools for probing the functions of glycosaminoglycans and for studying their interactions with proteins

Pulsed-Addition Ring-Opening Metathesis Polymerization: Catalyst-Economical Syntheses of Homopolymers and Block Copolymers

Poly(tert-butyl ester norbornene imide) homopolymers and poly(tert-butyl ester norbornene imide-b-N-methyloxanorbornene imide) copolymers were prepared by pulsed-addition ring-opening metathesis polymerization (PA-ROMP). PA-ROMP is a unique polymerization method that employs a symmetrical cis-olefin chain transfer agent (CTA) to simultaneously cap a living polymer chain and regenerate the ROMP initiator with high fidelity. Unlike traditional ROMP with chain transfer, the CTA reacts only with the living chain end, resulting in narrowly dispersed products. The regenerated initiator can then initiate polymerization of a subsequent batch of monomer, allowing for multiple polymer chains with controlled molecular weight and low polydispersity to be generated from one metal initiator. Using the fast-initiating ruthenium metathesis catalyst (H_2IMes)(Cl)_2(pyr)_2RuCHPh and cis-4-octene as a CTA, the capabilities of PA-ROMP were investigated with a Symyx robotic system, which allowed for increased control and precision of injection volumes. The results from a detailed study of the time required to carry out the end-capping/initiator-regeneration step were used to design several experiments in which PA-ROMP was performed from one to ten cycles. After determination of the rate of catalyst death, a single, low polydispersity polymer was prepared by adjusting the amount of monomer injected in each cycle, maintaining a constant monomer/catalyst ratio. Additionally, PA-ROMP was used to prepare nearly perfect block copolymers by quickly injecting a second monomer at a specific time interval after the first monomer injection, such that chain transfer had not yet occurred. Polymers were characterized by gel permeation chromatography with multiangle laser light scattering

Multiple Projection Optical Diffusion Tomography with Plane Wave Illumination

We describe a new data collection scheme for optical diffusion tomography in which plane wave illumination is combined with multiple projections in the slab imaging geometry. Multiple projection measurements are performed by rotating the slab around the sample. The advantage of the proposed method is that the measured data can be much more easily fitted into the dynamic range of most commonly used detectors. At the same time, multiple projections improve image quality by mutually interchanging the depth and transverse directions, and the scanned (detection) and integrated (illumination) surfaces. Inversion methods are derived for image reconstructions with extremely large data sets. Numerical simulations are performed for fixed and rotated slabs

Fluorescent detection of hydrogen sulfide (H2S) through the formation of pyrene excimers enhances H2S quantification in biochemical systems

Hydrogen sulfide (H2S) is produced endogenously by several enzymatic pathways and modulates physiological functions in mammals. Quantification of H2S in biochemical systems remains challenging because of the presence of interferents with similar reactivity, particularly thiols. Herein, we present a new quantification method based on the formation of pyrene excimers in solution. We synthesized the probe 2-(maleimido)ethyl 4-pyrenylbutanoate (MEPB) and determined that MEPB reacted with H2S in a two-step reaction to yield the thioether-linked dimer (MEPB)2S, which formed excimers upon excitation, with a broad peak of fluorescence emission centered at 480 nm. In contrast, we found that the products formed with thiols showed peaks at 378 and 398 nm. The difference in emission between the products prevented the interference. Furthermore, we showed that the excimer fluorescence signal yielded a linear response to H2S, with a limit of detection of 54 nM in a fluorometer. Our quantification method with MEPB was successfully applied to follow the reaction of H2S with glutathione disulfide and to quantify the production of H2S from cysteine by Escherichia coli. In conclusion, this method represents an addition to the toolkit of biochemists to quantify H2S specifically and sensitively in biochemical systems.MEC: I/FVF2017/069ANII: FCE_1_2017_1_136043CSIC: I+D 2017; I+D 202