Alexander H. Soeriyadi

Investigation into thiol-(meth)acrylate Michael addition reactions using amine and phosphine catalysts

This work describes a study into thiol–ene based Michael addition reactions. Different catalysts, primary and tertiary amines and phosphines, were investigated for the reaction of a range of thiols with dimers and oligomers of some (meth)acrylates. Primary and tertiary amines are efficient catalysts for the thiol–ene reaction, although these catalysts require several hours to reach high conversion. Moreover, the phosphine catalysts, dimethylphenylphosphine (DMPP) and tris-(2-carboxyethyl)phosphine (TCEP), were investigated in detail. DMPP is an efficacious catalyst yielding complete conversion in few minutes under optimized conditions. Importantly, the concentration of DMPP should be kept at catalytic levels to avoid the formation of by-products, originating from the addition of DMPP to the vinyl group. Furthermore, TCEP is an efficient catalyst for thiol–ene reactions in aqueous media when the pH of the medium is higher than 8.0 since at acidic pH the formation of by-products is observed.

Synthesis and modification of thermoresponsive poly(oligo(ethylene glycol) methacrylate) via catalytic chain transfer polymerization and thiol–ene Michael addition

Various poly(oligo(ethylene glycol) methyl ether methacrylate)s (POEGMEMAs) have been prepared by Catalytic Chain Transfer Polymerization (CCTP) using a range of OEGMEMA monomers (molecular weight from 180 to 1100 g mol−1). The chain transfer constants of bis(boron difluorodimethylglyoximate) cobalt(II) (CoBF) were determined and are reported for each monomer. The copolymerization of POEGMEMA (Mn = 475 g mol−1) with diethylene glycol methyl ether methacrylate (DEGMEMA) yielded thermoresponsive polymers. The lower critical solution temperatures (LCSTs) of the polymer chains can be tuned by the copolymer composition over the range 30 °C to 95 °C. In addition, the presence of the vinylic end-group, characteristic of CCT polymerization, provided further scope for post-synthetic modification via thiol–ene click chemistry, through nucleophilic Michael addition with various functional thiol compounds such as 2-mercaptoethanol, 3-mercaptopropionic acid, benzyl mercaptan and 1-dodecanethiol. The thiol–ene reaction was rigorously tested, optimized and characterized in this study in terms of solvents and most importantly the choice of the catalyst: dimethyl phenyl phosphine, tertiary amine or hexylamine. The optimum conditions reported allow near-quantitative functionalization of these macromonomers without significant side reactions. The effect of the end-group on the LCST has also been investigated, as well as thermal stability temperature of the copolymers.

Flame oxidation of stainless steel felt enhances anodic biofilm formation and current output in bioelectrochemical systems

Stainless steel (SS) can be an attractive material to create large electrodes for microbial bioelectrochemical systems (BESs), due to its low cost and high conductivity. However, poor biocompatibility limits its successful application today. Here we report a simple and effective method to make SS electrodes biocompatible by means of flame oxidation. Physicochemical characterization of electrode surface indicated that iron oxide nanoparticles (IONPs) were generated in situ on an SS felt surface by flame oxidation. IONPs-coating dramatically enhanced the biocompatibility of SS felt and consequently resulted in a robust electroactive biofilm formation at its surface in BESs. The maximum current densities reached at IONPs-coated SS felt electrodes were 16.5 times and 4.8 times higher than the untreated SS felts and carbon felts, respectively. Furthermore, the maximum current density achieved with the IONPs-coated SS felt (1.92 mA/cm(2), 27.42 mA/cm(3)) is one of the highest current densities reported thus far. These results demonstrate for the first time that flame oxidized SS felts could be a good alternative to carbon-based electrodes for achieving high current densities in BESs. Most importantly, high conductivity, excellent mechanical strength, strong chemical stability, large specific surface area, and comparatively low cost of flame oxidized SS felts offer exciting opportunities for scaling-up of the anodes for BESs.

Stimuli-responsive functionalized mesoporous silica nanoparticles for drug release in response to various biological stimuli

A silica-based mesoporous nanosphere (MSN) controlled-release drug delivery system has been synthesized and characterized. The system uses l-cysteine derivatized gold nanoparticles (AuNPs), bound to the MSNs using Cu2+ as a bridging ion. The AuNPs serve as removable caps that hinder the release of drug molecules inside the amino functionalized MSN mesoporous framework. The modified MSNs themselves exhibit negligible cytotoxicity to living cells, as revealed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The drug delivery system requires one of two biological stimuli to trigger drug release. These stimuli are either: low pH (pH < 5); or elevated levels of adenosine triphosphate (ATP) (concentration > 4 mM). The feasibility of biologically controlled release was demonstrated through the stimuli-induced removal of the AuNP caps over the MSN releasing the anticancer drug doxorubicin. We envisage that this MSN system could play a significant role in developing new generations of controlled-release delivery vehicles.

Polymersomes Prepared from Thermoresponsive Fluorescent Protein–Polymer Bioconjugates: Capture of and Report on Drug and Protein Payloads

Polymersomes provide a good platform for targeted drug delivery and the creation of complex (bio)catalytically active systems for research in synthetic biology. To realize these applications requires both spatial control over the encapsulation components in these polymersomes and a means to report where the components are in the polymersomes. To address these twin challenges, we synthesized the protein-polymer bioconjugate PNIPAM-b-amilFP497 composed of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) and a green-fluorescent protein variant (amilFP497). Above 37 °C, this bioconjugate forms polymersomes that can (co-)encapsulate the fluorescent drug doxorubicin and the fluorescent light-harvesting protein phycoerythrin 545 (PE545). Using fluorescence lifetime imaging microscopy and Förster resonance energy transfer (FLIM-FRET), we can distinguish the co-encapsulated PE545 protein inside the polymersome membrane while doxorubicin is found both in the polymersome core and membrane.

Adsorption behaviour of sulfur containing polymers to gold surfaces using QCM-D

We investigate the influences that functional group, polymer molecular weight and polymer molecular architecture have on the adsorption behaviour of some sulfur containing oligo(ethylene glycol) polymers to gold. QCM-D and XPS was used in this investigation revealing that disulfide functional groups bind with more mass deposited than dithio, trithio or thiols. This was observed with small di(ethylene glycol) polymers and with higher mass polymers. The effect of the sulfo-groups was not as apparent with higher mass polymers. Longer PEG pendent chains resulted in lower binding overall on the gold surface in comparison to shorter DEG chains caused by shielding of sulfur by the longer pendent chains. Thiols undergo two steps during the adsorption process while all other sulfur species adsorb in one step. XPS revealed the dissociation of disulfide bonds when binding to gold. These findings are important when forming stable polymer films on gold efficiently, with uses in applications from bio-fouling to polymer-lipid bilayers.

Synthesis and high-throughput processing of polymeric hydrogels for 3D cell culture.

3D cell cultures have drawn a large amount of interest in the scientific community with their ability to closely mimic physiological conditions. Hydrogels have been used extensively in the development of extracellular matrix (ECM) mimics for 3D cell culture. Compounds such as collagen and fibrin are commonly used to synthesize natural ECM mimics; however they suffer from batch-to-batch variation. In this Review we explore the synthesis route of hydrogels; how they can be altered to give different chemical and physical properties; how different biomolecules such as arginylglycylaspartic acid (RGD) or vascular endothelial growth factor (VEGF) can be incorporated to give different biological cues; and how to create concentration gradients with UV light. There will also be emphasis on the types of techniques available in high-throughput processing such as nozzle and droplet-based biofabrication, photoenabled biofabrication, and microfluidics. The combination of these approaches and techniques allow the preparation of hydrogels which are capable of mimicking the ECM.

Reversible gating of smart plasmonic molecular traps using thermoresponsive polymers for single-molecule detection.

Single-molecule surface-enhanced Raman spectroscopy (SERS) has attracted increasing interest for chemical and biochemical sensing. Many conventional substrates have a broad distribution of SERS enhancements, which compromise reproducibility and result in slow response times for single-molecule detection. Here we report a smart plasmonic sensor that can reversibly trap a single molecule at hotspots for rapid single-molecule detection. The sensor was fabricated through electrostatic self-assembly of gold nanoparticles onto a gold/silica-coated silicon substrate, producing a high yield of uniformly distributed hotspots on the surface. The hotspots were isolated with a monolayer of a thermoresponsive polymer (poly(N-isopropylacrylamide)), which act as gates for molecular trapping at the hotspots. The sensor shows not only a good SERS reproducibility but also a capability to repetitively trap and release molecules for single-molecular sensing. The single-molecule sensitivity is experimentally verified using SERS spectral blinking and bianalyte methods.

Effect of TiO2 nanoparticle surface functionalization on protein adsorption, cellular uptake and cytotoxicity: the attachment of PEG comb polymers using catalytic chain transfer and thiol–ene chemistry

A successful modification of titanium dioxide (TiO2) nanoparticles surfaces by a grafting-to polymer technique combining catalytic chain transfer and thiol–ene click chemistry is reported. Vinylic end functional polymers were first prepared by catalytic chain transfer polymerization (CCTP) using oligo(ethylene glycol) methacrylate as a monomer. The presence of vinylic end groups was then exploited to attach the polymers to thiol functionalized TiO2 nanoparticles via thiol–ene Michael nucleophilic reactions. X-ray photoelectron spectroscopy (XPS), attenuated total reflectance-infrared (ATR-IR), dynamic light scattering (DLS), and thermogravimetric analyses (TGA) were used to verify the successful modification of the TiO2 surface. The modified TiO2 nanoparticles were stable in cell culture media and formed smaller aggregates when compared to non-surface modified nanoparticles. Cellular toxicity of the hybrid TiO2–polymer particles towards human lung cell lines A549 and H1299 in vitro was evaluated. Results from one-dimensional gel electrophoresis show the presence of polymer layers around the particles affects the adsorption of protein onto the TiO2 surface. The reduction in particle aggregate size and changes to the particle surface chemistry, following polymer grafting, was found to reduce cellular uptake and diminish cytotoxicity for both human lung cell lines tested.

Optimising the enzyme response of a porous silicon photonic crystal via the modular design of enzyme sensitive polymers

We describe the immobilization within the pores of a porous silicon photonic crystal of an enzyme degradable polymer network, for optical biosensing. A porous silicon (PSi) rugate filter is a one-dimensional photonic crystal with a high-reflectivity optical resonance that is sensitive to small changes in the refractive index of the pore space permeating through the structure. An enzymatically degradable polymer network was constructed by first “clicking” an antifouling copolymer, poly(oligo ethylene glycol-co-acrylic acid)-N3, to an alkyne functionalized PSi surface via copper(I)-catalysed alkyne–azide cycloaddition (CuAAC) reaction. MMP-2 or MMP-9 specific cleavable peptide sequences, with diamine functional groups, were then added, using a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide/N-hydroxysuccinimide (EDC/NHS) chemistry to react with the acrylic acid group. The polymer network was completed by further attachment of a sacrificial polymer, poly(hydroxyethyl acrylate-co-N-hydroxysuccinimide ester acrylate). X-ray photoelectron spectroscopy (XPS) and optical reflectivity measurements reveal successful modification of the PSi with the polymer–peptide network. Exposure of the biosensor platform to solutions of matrix metalloproteinases, MMP-2 or MMP-9, caused a change in the average refractive index of the photonic crystal, resulting in a discernible blue shift in the reflectivity spectra. The blue shift indicated the degradation of the polymer network within the porous network. Selective detection of different MMPs was demonstrated, via the use of different peptide sequences, which are selectively digestible by different MMPs, to link the two polymers.