thiol-Michael Addition Research Articles

Site-Specific Cross-Linking of Galectin-1 Homodimers via Poly(ethylene glycol) Bismaleimide.

The promise of the natural immunoregulator, Galectin-1 (Gal1), as an immunomodulatory therapeutic is challenged by its unstable homodimeric conformation. Previously, a Gal1 homodimer stabilized via covalent poly(ethylene glycol) diacrylate (PEGDA) cross-linking demonstrated higher activity relative to the non-covalent homodimer. Here, we report Gal1 homodimers formed using an alternative thiol-Michael addition linker chemistry. Poly(ethylene glycol) bismaleimide (PEGbisMal) reacted with Gal1 at multiple sites with greater efficiency than PEGDA. However, multiple PEGbisMal molecules were conjugated to Gal1 C130, a Gal1 mutant with one surface cysteine (cys-130) and two cysteines thought to be buried in the solvent-inaccessible protein core (cys-42 and cys-60). Site-directed mutagenesis demonstrated that cys-60 was the site at which additional PEGbisMal molecules were conjugated onto Gal1 C130. Compared to WT-Gal1, Gal1 C130 had low activity for inducing Jurkat T cell death, characterized by phosphatidylserine exposure and membrane permeability. PEG cross-linking could restore the function of Gal1 C130, such that at high concentrations Gal1 C130 cross-linked by PEGbisMal had higher activity than both WT-Gal1 and Gal1 C130 cross-linked by PEGDA. Mutating cys-42 and cys-60 to serines in Gal1 C130 did not affect the cell death signaling activity of the Gal1 C130 homodimer cross-linked by PEGbisMal. PEGylated Gal1 C130 variants also eliminated the need for a reducing agent, such as dithiothreitol, which is required to maintain WT-Gal1 signaling activity. Collectively, these data demonstrate that thiol-Michael addition bioconjugation leads to a PEG-cross-linked Gal1 homodimer with improved extracellular signaling activity that does not require a reducing environment to be functional.

Direct and Indirect Biomimetic Peptide Modification of Alginate: Efficiency, Side Reactions, and Cell Response.

In the fast-developing field of tissue engineering there is a constant demand for new materials as scaffolds for cell seeding, which can better mimic a natural extracellular matrix as well as control cell behavior. Among other materials, polysaccharides are widely used for this purpose. One of the main candidates for scaffold fabrication is alginate. However, it lacks sites for cell adhesion. That is why one of the steps toward the development of suitable scaffolds for cells is the introduction of the biofunctionality to the alginate structure. In this work we focused on bone-sialoprotein derived peptide (TYRAY) conjugation to the molecule of alginate. Here the comparison study on four different approaches of peptide conjugation was performed including traditional and novel modification methods, based on 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxy succinimide (EDC/NHS), 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride (DMTMM), thiol-Michael addition and Cu-catalyzed azide–alkyne cycloaddition reactions. It was shown that the combination of the alginate amidation with the use of and subsequent Cu-catalyzed azide–alkyne cycloaddition led to efficient peptide conjugation, which was proven with both NMR and XPS methods. Moreover, the cell culture experiment proved the positive effect of peptide presence on the adhesion of human embryonic stem cells.

Cover Feature: Polydopamine‐Mediated Surface Functionalization of Exosomes (ChemNanoMat 6/2021)

Exosomes were non-covalently functionalized using the self-polymerization of dopamine and subsequent PEGylation via Thiol-Michael addition. This rapid and versatile exosome coating method improved the colloidal stability of exosomes and endowed them with tunable fluorescence and coating thickness. Collectively, this aggregation-free non-covalent coating approach expands the potential of exosomes in various applications without requiring complex equipment or reagents. More information can be found in the Communication by Hirotaka Ejima et al.

Thiol-terminated nanodiamond powders for support of gold nanoparticle catalysts

Surface-functionalized nanodiamond (ND) is a promising material for nanomedicine and nanotechnology applications. Among the surface functionalizations developed for ND, thiol-termination has received relatively little attention. Here we describe a new method of thiolating the surface of detonation and high-pressure high-temperature ND by treatment with elemental sulfur at 450 °C, followed by reduction of surface-bound sulfur moieties. The surface composition of the functionalized ND was characterized using X-ray photoelectron spectroscopy and transmission electron microscopy. Analysis revealed the presence of both sulfur in the thiol oxidation state and oxygen, indicating that the surface was partially modified with thiols with no graphitization of the diamond surface detected. The surface thiols participated in a thiol-Michael addition with fluorescein-5-maleimide, demonstrating the utility of the thiols for conjugation of molecules to the diamond surface. Thiolated detonation ND was used as a support for gold (Au) nanoparticles (NPs) formed by in situ reduction of Au salt at 250 °C. The thiol-terminated ND stabilized the Au NPs, maintaining the small (~4 nm) size, whereas aggregates formed on ND powder with an oxygenated surface. The supported Au NPs catalyzed the reduction of resazurin, indicating that the active sites were not passivated by interaction with the ND surface thiols.

Durable superhydrophobic cotton fabrics prepared by surface-initiated electrochemically mediated ATRP of polyhedral vinylsilsesquioxane and subsequent fluorination via thiol-Michael addition reaction

Fluorinated polyhedral oligomeric silsesquioxane (F-POSS) is one of the most popular candidates at present for superhydrophobic coating. Because of its ultralow surface energy, F-POSS has usually been dissolved with expensive fluoro-solvents, and the melting temperature of F-POSS is not high (122–140 °C), which will cause its loss during use. So trying to polymerize/crosslink F-POSS molecules and/or directly graft F-POSS to substrate is important. In this work, we report the SI-eATRP grafting of methacryl POSS (MA-POSS) on cotton and the subsequent amine catalyzed thiol-methacrylate Michael addition reaction of poly(MA-POSS) with 1H, 1H, 2H, 2H-perfluorododecyl-1-thiol (PFDT) for the fabrication of a durable poly(MA-POSS)-PFDT coating. The cotton fabric coated with poly(MA-POSS) was nearly superhydrophobic after 4 h of SI-eATRP process under potentiostatic condition of −0.40 V. Although the water contact angle (WCA) was ~148°, water droplets tended to adhere to the cotton fabric surface even when the fabric was turned upside down. After fluorination, WCA was increased to ~160°, and water drops could slide off when the fabric was slightly tilted. The sliding angle (SA) was ~10°. The as-prepared poly(MA-POSS)-PFDT coating was durable against repeated washing and physical abrasion. After 30 accelerated washing cycles (equals to 150 home laundering cycles), the coated fabric still showed superhydrophobicity. After 800 abrasion cycles over sandpaper, the WCA was still as high as 149°. In addition, the coated fabric had self-healing ability and could restore its superhydrophobicity after plasma etching through heat treatment. After 10 cycles of plasma etching and heat-induced healing process, the WCA of the coated fabric kept at ~154°. Such a durable superhydrophobic fabric coating may find applications in the development of functional clothing for a variety of purposes.

Single-Cell Phenotypic Analysis and Digital Molecular Detection Linkable by a Hydrogel Bead-Based Platform.

Cell heterogeneity, such as antibiotic heteroresistance and cancer cell heterogeneity, has been increasingly observed. To probe the underlying molecular mechanisms in the dynamically changing heterogeneous cells, a high throughput platform is urgently needed to establish single cell genotype-phenotype correlations. Herein, we report a platform combining single-cell viability phenotypic analysis with digital molecular detection for bacterial cells. The platform utilizes polyethylene glycol hydrogel that cross-links through a thiol-Michael addition, which is biocompatible, fast, and spontaneous. To generate uniform nanoliter-sized hydrogel beads (Gelbeads), we developed a convenient and disposable device made of needles and microcentrifuge tubes. Gelbead-based single cell viability and molecular detection assays were established. Enhanced thermal stability and uncompromised efficiency were achieved for digital polymerase chain reaction (PCR) and digital loop-mediated isothermal amplification (LAMP) within the Gelbeads. Reagent exchange for in situ PCR following viability phenotypic analyses was demonstrated. The combined analyses may address the genotypic differences between cellular subpopulations exhibiting distinct phenotypes. The platform promises unique perspectives in mechanism elucidation of environment-evolution interaction that may be extended to other cell types for medical research.

Enamine Organocatalysts for the Thiol-Michael Addition Reaction and Cross-Linking Polymerizations

This article describes an efficient enamine organocatalyzed thiol-Michael click reaction and its broad application in cross-linking polymerizations. A series of enamines was shown to catalyze the t...

Engineering Modular Half-Antibody Conjugated Nanoparticles for Targeting CD44v6-Expressing Cancer Cells.

Gastric cancer (GC) remains a major cause of death worldwide mainly because of the late detection in advanced stage. Recently, we proposed CD44v6 as a relevant marker for early detection of GC, opening new avenues for GC-targeted theranostics. Here, we designed a modular nanoscale system that selectively targets CD44v6-expressing GC cells by the site-oriented conjugation of a new-engineered CD44v6 half-antibody fragment to maleimide-modified polystyrene nanoparticles (PNPs) via an efficient bioorthogonal thiol-Michael addition click chemistry. PNPs with optimal particle size (200 nm) for crossing a developed biomimetic CD44v6-associated GC stromal model were further modified with a heterobifunctional maleimide crosslinker and click conjugated to the novel CD44v6 half-antibody fragment, obtained by chemical reduction of full antibody, without affecting its bioactivity. Collectively, our results confirmed the specific targeting ability of CD44v6-PNPs to CD44v6-expressing cells (1.65-fold higher than controls), highlighting the potential of CD44v6 half-antibody conjugated nanoparticles as promising and clinically relevant tools for the early diagnosis and therapy of GC. Additionally, the rational design of our nanoscale system may be explored for the development of several other nanotechnology-based disease-targeted approaches.

Phosphonium Tetraphenylborate: A Photocatalyst for Visible-Light-Induced, Nucleophile-Initiated Thiol-Michael Addition Photopolymerization.

A photoinitiation system that utilizes phosphonium tetraphenylborate as the key component was developed for the visible light-triggered nucleophile-catalyzed thiol-Michael addition reaction. This highly reactive catalyst was composed of a photocaged phosphine (methyldiphenylphosphonium tetraphenylborate, MDPP·HBPh4), a photosensitizer (isopropylthioxanthone, ITX), and a radical scavenger (TEMPO). Unlike the prevailing photobase catalysts, this photoactivatable phosphine system triggers the thiol-Michael addition polymerization by a nucleophile-catalyzed mechanism and provides a controlled stoichiometric reaction between the thiol and the vinyl precursors. This approach enables the formation of homogeneous polymer networks upon low-energy visible light exposure and, thus, broadens its potential applications in bulk polymer materials synthesis and UV-sensitive bioscaffold formation.

Closed-cell, phase change material-encapsulated, emulsion-templated monoliths for latent heat storage: Flexibility and rapid preparation

While phase change material (PCM)-encapsulated polyHIPE monoliths are advantageous for latent heat storage, brittleness and time-consuming preparation hinder their wide application. Herein, we report the rapid fabrication of closed-cell, flexible monoliths through emulsion templating in seconds through ammonia-catalyzed interfacial thiol-Michael addition. Using an organic PCM (octodecane, OD) as the dispersed phase, OD-encapsulated monoliths with flexibility were fabricated for the first time. The monoliths exhibited high flexibility at temperature over 30 °C and robust compressive property. The OD-encapsulated monoliths possessed extremely high heat capacity (up to 213 J/g, ~90% pure OD), and high reusability/stability (without obvious deterioration in heat capacity after 100 heating/cooling cycles). The feature that combines the rapid synthesis, high flexibility, mechanical robustness, high heat capacity and good reusability/stability enabled the OD-encapsulated monoliths to be excellent candidates for latent heat storage.

Bifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis.

To improve the field of catalysis, there is a substantial and growing need for novel high-performance catalysts providing new reactivity. To date, however, the set of reactions that can be reliably performed to prepare chiral compounds in largely one enantiomeric form using chiral catalysts still represents a small fraction of the toolkit of known transformations. In this context, chiral Brønsted bases have played an expanding role in catalyzing enantioselective reactions between various carbon- and heteroatom-centered acids and a host of electrophilic reagents. This Account describes our recent efforts developing and applying a new family of chiral Brønsted bases incorporating an H-bond donor moiety and a strongly basic iminophosphorane, which we have named BIMPs (Bifunctional IMinoPhosphoranes), as efficient catalysts for reactions currently out of reach of more widespread tertiary amine centered bifunctional catalysts. The iminophosphorane Brønsted base is easily generated by the Staudinger reaction of a chiral organoazide and commercially available phosphine, which allows easy modification of the catalyst structure and fine-tuning of the iminophosphorane pKBH+. We have demonstrated that BIMP catalysts can efficiently promote the enantioselective addition of nitromethane to low reactivity N-diphenylphosphinoyl (DPP)-protected imines of ketones (ketimines) to access valuable chiral diamine and α-quaternary amino acid building blocks, and later extended this methodology to phosphite nucleophiles. Subsequently, the reaction scope was expanded to include the Michael addition of high pKa alkyl thiols to α-substituted acrylate esters, β-substituted α,β-unsaturated esters, and alkenyl benzimidazoles as well as the challenging direct aldol addition of aryl ketones to α-fluorinated ketones. Finally, BIMP catalysts were shown to be used in key steps in the synthesis of complex alkaloid natural products (-)-nakadomarin A and (-)-himalensine A, as well as in polymer synthesis. In most cases, the predictable nature of the BIMP promoted reactions was demonstrated by multigram scale-up while employing low catalyst loadings (down to 0.05 mol%). Furthermore, it was shown that BIMP catalysts can be easily immobilized onto a solid support in one-step for increased catalyst recycling and flow chemistry applications. Alongside our own work, this Account also includes elegant work by Johnson and co-workers utilizing the BIMP catalyst system, when alternative catalysts proved suboptimal.

Organocatalytic Michael Addition as a Method for Polyisobutylene Chain‐End Functionalization

Front Cover: In article number 2000382 Mohammed Al-Hashimi, Hassan S. Bazzi and co-workers adapt the organocatalyzed aza- and thiol-Michael addition ‘click’ reaction to polyisobutylene acrylate functionalization. This approach paves the way to a myriad of chain-end functional polyolefins with a broad range of potential applications.

Organocatalytic Michael Addition as a Method for Polyisobutylene Chain-End Functionalization.

Functionalization of polyolefins, in particular polyisobutylene, remains a relatively unexplored application for the Michael reaction. This work evaluates the potential of polyisobutylene acrylate (PIBA) chain-end modification via organocatalyzed thiol-Michael and aza-Michael additions. A series of chain-end functional polyisobutylene oligomers are prepared using "click" reactions of thiols or amines to PIBA in the presence of 0.02 equivalents of organocatalyst. Reaction kinetics and chain-end transformations are monitored using NMR spectroscopy and the macromolecular products are characterized by size exclusion chromatography. Further potential of this synthetic strategy is illustrated by thiol-Michael addition of thiols formed in situ via nucleophilic thiolactone ring opening. The obtained results provide an efficient method for the preparation of functional polyisobutylene oligomers that can be utilized in a broad range of potential applications.

Phototriggered Base Amplification for Thiol-Michael Addition Reactions in Cross-linked Photopolymerizations with Efficient Dark Cure

In the present work, the photocatalytic activity was investigated toward a thiol-Michael reaction of different combinations of 9-fluorenylmethyl carbamate (Fmoc) derivatives and photocaged amines (PCA) as base amplifiers and the catalytic base, respectively. This phototriggering approach was systematically studied for evaluating its effect on kinetics between thiol and Michael acceptors like acrylate or sulfone wherein, butyl 3-mercaptopropionate (BMP), 1-hexyl acrylate (HA), and ethyl vinyl sulfone (EVS) were used as model reactants. Interestingly, PCAs exhibited low quantum yields by themselves; NPPOC-Hex (2.5 mol %) which when used with BMP and HA, resulted in only 25% thiol conversion; however, when used along with Fmoc-Hex or Fmoc-TMG (2.5 or 5 mol %), it resulted in a higher thiol conversion of 50–60%. Furthermore, use of NPPOC-DEA (5 mol %) with 1 mol % Fmoc-TMG resulted in >70% thiol conversion for the same system. Upon using BMP and EVS nearly complete conversion of functional groups with 5 mol % NPPOC-DEA and 5 mol % Fmoc-DEA was obtained. This enhancement in reaction kinetics and conversion upon addition of an Fmoc derivative to a monofunctional thiol-Michael system was extended to multifunctional derivatives for polymerizing cross-linked polymer networks. Moreover, the kinetic study on model reactants also demonstrated efficient dark curing, resulting in 50–75% thiol conversion with only 30 s irradiation time, leading to validation of the efficacy of Fmoc derivatives and PCAs as photocatalysts for dark cure. Upon precise characterization in cross-linked systems using Raman spectroscopy for TMPTA/PETMP in the presence of 20 mol % NPPOC-DEA and 1 mol % Fmoc-TMG, the extent of dark cure was evaluated for a distance of 16.5 mm, which was observed to undergo maximum conversion and high dark cure propagation upon heating to 70 °C. Therefore, Fmoc-PCA catalysis is a practically useful approach for improving the photoinitiated efficiency of the thiol-Michael reaction and enabling photopolymerization in the dark with a marked improvement in photosensitivity.

Contrastive study on β-cyclodextrin polymers resulted from different cavity-modifying molecules as efficient bi-functional adsorbents

The adsorption capacity of existing β-CD-based adsorbents is generally restrained by the limited dimension of β-CD's inherent cavity. To find an effective way to expand the inclusion/adsorption capacity of β-CD, a series of N-containing groups, amine with straight chain, imidazole with rigid five-membered ring and pyridine with rigid six-membered ring, are firstly utilized to alkylate the secondary rim of β-CD through the thiol-Michael addition. The capsulation ability of the resultant β-CD derivatives are compared and the β-CD derivatives appended with aromatic imidazole or pyridine provide extremely rich host surroundings for loading Rhodamine B (RB), which is identified by the 1H NMR titration and UV–Vis spectroscopy. The bi-functional adsorbents correlative to those β-CD derivatives are then synthesized by the polymerization of vinylated β-CD and the corresponding vinyl N-containing monomers, and applied to remove RB and Cd (II) from the aqueous condition. Governed by multiple factors such as porosity, surface charge and binding affinity, the imidazole modified β-CD adsorbent revealed the best adsorption efficiency for organic dyes and metal ions, in both single- and bi-component solutions. Our work provides effective strategy and reliable basis for the design and fabrication of β-CD-based materials with high capacity and multi-functionality.

Dual charged folate labelled chitosan nanogels with enhanced mucoadhesion capacity for targeted drug delivery

Nanometric gel particles (CsSH/PEGBCOOH) were successfully synthesized through water in oil (W/O) emulsion by the covalent cross–linking between the primary amines of thiolated chitosan (CsSH) and the dicarboxylic poly(ethylene glycol) (PEG) derivative as cross–linker (PEGBCOOH). Thus, the amidation reaction led to the formation of stable nanosized networks positively or negatively charged by the ionization of either amines or thiol moieties depending on the surrounding pH. This double response, which has not been studied before, was markedly observed and quantified during the characterization of the nanogels, concluding the high impact that could suppose these promising nanoparticles in the biomedical field. Besides, the presence of thiol groups in the nanogels was demonstrated to greatly improve the nanoparticle–mucus interactions, highlighting the potential of this novel strategy in the field of nanotechnology. Finally, nanogels were further labelled with folate ligand as an example of a simple and easy functionalization route via thiol–Michael addition (MA) reaction for future studies of tumour targeting therapies of these nanocarriers. Therefore, the synthesized chitosan–based labelled nanogels presented an adaptable character to the environmental conditions due to their dual pH response and mucoadhesion capacity, making them great candidates as nanocarriers for biomedical applications.

Modification of graphene oxide with acrylate phosphorus monomer via thiol-Michael addition click reaction to enhance the anti-corrosive performance of waterborne epoxy coatings

To develop a convenient way to functionalize graphene oxide (GO) for corrosion protective coatings, a commercial acrylate phosphorus functional monomer (SIPOMER PAM100) was used to modify thiol-terminated GO via thiol-Michael addition click reaction. Subsequently, PAM100 modified GO (PGO) was introduced to waterborne epoxy coating as a nanofiller for anticorrosion reinforcement. The anticorrosive performance of PGO/WEP nanocomposite coatings was evaluated by electrochemical impedance spectroscopy (EIS). Results obtained from FT-IR, XRD, Raman, SEM and SEM-EDS show that PAM100 is successfully grafted to the surface of GO using γ-Mercaptopropyl triethoxysilane (KH-580) as a bridge molecule. It is clear that PGO distributes homogenously within WEP matrix from SEM images. After 40-day exposure to 3.5 wt.% NaCl solution, the |Z|0.01Hz of blank WEP suffers a serious decrease (from 9.83 × 107 Ω·cm2 to 4.93 × 106 Ω·cm2) while PGO/WEP has a relatively smaller change in |Z|0.01Hz (from 1.35 × 108 Ω·cm2 to 2.91 × 107 Ω·cm2). It demonstrated that PGO/WEP coating presents a superior corrosion resistance performance.

Stress Relaxation via Covalent Dynamic Bonds in Nanogel-Containing Thiol-Ene Resins.

Functional nanogels are attractive additives for use in polymer composites. In this study, nanogels with internal allyl sulfide moieties throughout their network structure were prepared via a thiol-Michael addition reaction. The excess thiol-functionalized nanogels were less than 60 nm as discrete particles but act as room-temperature liquids in the bulk state. The reactive nanogels can be dispersed in and swollen by a thiol-ene matrix resin, which upon photopolymerization yields dramatically decreased levels of polymerization shrinkage stress. Furthermore, the postcured nanogel-modified polymers effectively relaxed applied stresses as well as enhanced toughness during exposure to a UV light source that activated the addition-fragmentation as a means for dynamic bond exchange. These nanogels provide a generic approach to introduce adaptable network performance that significantly improves a number of key properties of glassy cross-linked polymer.

Selective Maleylation-Directed Isobaric Peptide Termini Labeling for Accurate Proteome Quantification.

Isobaric peptide termini labeling (IPTL) is an attractive protein quantification method because it provides more accurate and reliable quantification information than traditional isobaric labeling methods (e.g., TMT and iTRAQ) by making use of the entire fragment-ion series instead of only a single reporter ion. The multiplexing capacity of published IPTL implementations is, however, limited to three. Here, we present a selective maleylation-directed isobaric peptide termini labeling (SMD-IPTL) approach for quantitative proteomics of LysC protein digestion. SMD-IPTL extends the multiplexing capacity to 4-plex with the potential for higher levels of multiplexing using commercially available 13C/15N labeled amino acids. SMD-IPTL is achieved in a one-pot reaction in three consecutive steps: (1) selective maleylation at the N-terminus; (2) labeling at the ε-NH2 group of the C-terminal Lys with isotopically labeled acetyl-alanine; (3) thiol Michael addition of an isotopically labeled acetyl-cysteine at the maleylated N-terminus. The isobarically labeled peptides are fragmented into sets of b- and y-ion clusters upon LC-MS/MS, which convey not only sequence information but also quantitative information for every labeling channel and avoid the issue of ratio distortion observed with reporter-ion-based approaches. We demonstrate the SMD-IPTL approach with a 4-plex labeled sample of bovine serum albumin (BSA) and yeast lysates mixed at different ratios. With the use of SMD-IPTL for labeling and a narrow precursor isolation window of 0.8 Th with an offset of −0.2 Th, accurate ratios were measured across a 10-fold mixing range of BSA in a background of yeast proteome. With the yeast proteins mixed at ratios of 1:5:1:5, BSA was detected at ratios of 0.94:2.46:4.70:9.92 when spiked at 1:2:5:10 ratios with an average standard deviation of peptide ratios of 0.34.

Catalytic Generation of Nitric Oxide from Poly(ε-caprolactone)/Phosphobetainized Keratin Mats for a Vascular Tissue Engineering Scaffold.

Tissue-engineered vascular graft (TEVG) is a promising alternative to meet the clinical demand of organ shortages. Herein, human hair keratin was extracted by the reduction method, followed by modification with zwitterionic 2-methacryloyloxyethyl phosphorylcholine (MPC) through thiol-Michael addition to improve blood clotting nature. Then, phosphobetainized keratin (PK) was coelectrospun with poly(ε-caprolactone) (PCL) to afford PCL/PK mats with a ratio of 7:3. The surface morphology, chemical structure, and wettability of these mats were characterized. The biocomposite mats selectively enhanced adhesion, migration, and growth of endothelial cells (ECs) while suppressed proliferation of smooth muscle cells (SMCs) in the presence of glutathione (GSH) and GSNO due to the catalytic generation of NO. In addition, these mats exhibited good blood anticoagulant activity by reducing platelet adhesion, prolonging blood clotting time, and inhibiting hemolysis. Taken together, these NO-generating PCL/PK mats have potential applications as a scaffold for vascular tissue engineering with rapid endothelialization and reduced SMC proliferation.