Thiol-containing Molecules Research Articles

Nanoparticle Concentration vs Surface Area in the Interaction of Thiol-Containing Molecules: Toward a Rational Nanoarchitectural Design of Hybrid Materials.

The effect of accounting for the total surface in the association of thiol-containing molecules to nanosilver was assessed using isothermal titration calorimetry, along with a new open access algorithm that calculates the total surface area for samples of different polydispersity. Further, we used advanced molecular dynamic calculations to explore the underlying mechanisms for the interaction of the studied molecules in the presence of a nanosilver surface in the form of flat surfaces or as three-dimensional pseudospherical nanostructures. Our data indicate that not only is the total surface area available for binding but also the supramolecular arrangements of the molecules in the near proximity of the nanosilver surface strongly affects the affinity of thiol-containing molecules to nanosilver surfaces.

Modulating Thiol p Ka Promotes Disulfide Formation at Physiological pH: An Elegant Strategy To Design Disulfide Cross-Linked Hyaluronic Acid Hydrogels.

The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors, and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants, and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as l-cysteine indicated disulfide formation at a 2.8-fold higher ( k1 = 5.04 × 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid ( k1 = 1.80 × 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-l-cysteine substrate ( k1 = 0.51 × 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the p Ka value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the p Ka of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys); and 8.1 for HA-thiol (HA-SH) derivatives, respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 min or 10 h, respectively, at pH 7.4. After completion of cross-linking reaction, both gels demonstrated a storage modulus G' ≈ 3300-3500 Pa, which indicated comparable levels of cross-linking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.

Adsorption behaviors of deposition-targeted metallic ions onto thiol-containing silane modified liquid crystal polymer surfaces

Here we demonstrate the adsorption behaviors of typical deposition-targeted metallic (Ag, Cu or Ni) ions on thiol-end surfaces during electroless deposition using for fabricating flexible electronics. Specific thiol-containing silane molecules were assembled onto the corona activated liquid crystal polymer surfaces and then metallic ions were adsorbed onto the modified surfaces. By using X-ray photoelectron spectroscopy, scanning electron microscope and atomic force microscope, the assembly processes, inter-reaction mechanism of these ions with thiol-end groups, and adsorption behaviors have been investigated in details. Thickness of the molecule layer was estimated as some nanometers. Besides, zeta-potential and wettability were used to characterize the surfaces and verify the adsorption behaviors. Overall, this work provides a helpful contribution for understanding circuits' deposition processes and fabricating flexible patterns for electronic devices.

61 - Sulforaphane-mediated inhibition of SHP2 as a potential pharmacotherapy for Noonan syndrome

Sulforaphane (SFN) is an electrophilic isothiocyanate capable of post-translationally modifying protein cysteine thiolates. Immunoprecipitation using a validated polyclonal antibody developed in-house to pan-specifically detect SFN adducted to cysteines, combined with quantitative proteomics confirmed the protein tyrosine phosphatase SHP2 as a target of SFN in cardiac tissue of wildtype (WT) mice orally administered the compound. A chemically-stabilised variant of SFN known as Sulforadex (SFX-01), which was used in subsequent studies, inhibited recombinant SHP2 in vitro, as well as that in cardiac tissue of mice administered the compound for 7-days. We speculated that SFX-01 may be therapeutic in diseases where SHP2 is hyperactive, such as Noonan syndrome. Indeed, using a Noonan syndrome mouse model, Ptpn11D61G/+, SFX-01 time-dependently inhibited cardiac SHP2 activity. Ptpn11D61G/+ mice, like many humans with Noonan syndrome, show myeloproliferative disease characterised by increased white blood cell count, spleen size, as well as increased myeloid cell number in blood, bone marrow and spleen. Sustained treatment of Ptpn11D61G/+ mice with SFX-01 normalised these myeloproliferation indices towards WT levels. SFX-01 also attenuated spleen SHP2 phosphatase activity in both WT and Ptpn11D61G/+ mice, consistent with this inhibitory mechanism mediating the therapeutic action of this electrophilic drug. Biochemical analyses showed SFN induced SHP2 oxidation in cardiac tissue of WT and Ptpn11D61G/+ mice despite the electrophile itself not remaining conjugated to the phosphatase. Using bovine serum albumin or SHP2 with conjugated SFN, we observed transfer (i.e. trans-thiolation) of the adducted SFN to other thiol-containing molecules such as haemoglobin or glutathione. SFN-labelling studies with SHP2 cysteine-to-serine mutants support the concept that the electrophile initially adducts the phosphatase, but a proximal cysteine thiol mediates its removal, which is associated with the formation of an inhibitory disulfide bond. In conclusion, SFX-01 shows promise in the treatment of Noonan syndrome by normalising the hyperactive SHP2 phosphatase activity that characterises these patients.

Kinetico-mechanistic study on the reduction/complexation sequence of PtIV/PtII organometallic complexes by thiol-containing biological molecules

The kinetics of the reaction of [PtIV(4X-Cph,N,N’)Cl(Y)2] complexes (2-X-Y) (X = Cl or F and Y = OH or Cl) with biological thiols (glutathione, cysteine, thiolactic acid) and methionine, has been monitored by UV–Vis spectrophotometry. The reactions have been followed at varying pHs and chloride concentrations (within the physiological range) and different temperatures and pressures. The bis-chlorido derivatives, 2-X-Cl, have been found to react with cysteine, glutathione and thiolactic acid, while the bis-hydroxido 2-X-OH derivatives are not reduced due to the high potential of the PtIV/PtII pair, as measured in aqueous solution. The lack of reactivity of methionine is related with its tioether nature preventing deprotonation of the S donor. In all remaining cases, two consecutive reaction steps have been found to occur. For cysteine the two steps can be kinetically resolved, the first step being neatly related to a PtIV to PtII reduction and the second step corresponding to the substitution of the remaining Cl− ligand by cysteine. The nature of the second step has been also confirmed by ESI-MS, as well as by the associative character of the activation parameters determined (low ΔH╪ and very negative ΔS╪ and ΔV╪). For glutathione and thiolactic acid, the rate and thermal and pressure activation parameters for the reduction step has been found similar to that obtained for the reaction with cysteine, but the substitution step could not be resolved kinetically. The substitution step, as measured from the reduced [PtII(4X-Cph,N,N’)Cl] complex, is faster than the reduction process, and also much faster than that observed for the reaction with cysteine. In both cases the final product resulting for the reduction reactions corresponds thus to the final substituted complex as found for the reaction with cysteine.

Mechanistic Insights into UV-Initiated Thiol–Ene Reactions on Amorphous Carbon Films

Click chemistries provide a straightforward means of imparting a desired physical property, reactivity, or function to a material through the covalent attachment of molecules to its surface. We previously prepared amorphous carbon (aC) films with terminal thiol groups. These groups allowed us to uniformly modify or selectively pattern the surface with a light-promoted thiol–ene reaction. This work builds upon our previous success, generating vinyl-terminated aC films. The vinyl groups are also compatible with thiol–ene reactions but afford faster rates of attachment and greater coverage when compared to similar reaction conditions carried out on a thiol-aC film. To our surprise, thiol-containing molecules also attached to control surfaces containing terminal methyl groups or hydrogen atoms. With a series of experiments, we show that the formation of a thiyl radical precedes reaction with the surface and that the lamp output power influences both the rate and selectivity of this attachment. These results s...

The Meisenheimer Complex as a Paradigm in Drug Discovery: Reversible Covalent Inhibition through C67 of the ATP Binding Site of PLK1

The polo kinase family are important oncology targets that act in regulating entry into and progression through mitosis. Structure-guided discovery of a new class of inhibitors of Polo-like kinase 1 (PLK1) catalytic activity that interact with Cys67 of the ATP binding site is described. Compounds containing the benzothiazole N-oxide scaffold not only bind covalently to this residue, but are reversible inhibitors through the formation of Meisenheimer complexes. This mechanism of kinase inhibition results in compounds that can target PLK1 with high selectivity, while avoiding issues with irreversible covalent binding and interaction with other thiol-containing molecules in the cell. Due to renewed interest in covalent drugs and the plethora of potential drug targets, these represent prototypes for the design of kinase inhibitory compounds that achieve high specificity through covalent interaction and yet still bind reversibly to the ATP cleft, a strategy that could be applied to avoid issues with conventional covalent binders.

Biohybridization of Supported Gold Nanoassemblies on Silicon

Understanding the molecular interactions of bio-organic molecules with metal nanoassemblies on a semiconductor surface is important to developing potential applications involving hybrid bio-organic metal interfaces. Here, we provide the first study of room-temperature growth evolution of l-cysteine on three notable Au nanoassemblies supported on the Si(111)7×7 surface. Our results indicate unidentate and/or bidentate arrangement of adsorbed cysteine on the Si substrate through Si–N and/or Si–S linkages, while in coexistence with the supported Au monomers and dimers. Similar to thiol-containing molecules adsorbed on other noble metals, cysteine chemisorbs via the S atom in neutral form on the supported Au nanocrystallite film. On the supported gold honeycomb nanonetwork, cysteine undergoes unidentate chemisorption through the thiol group with Au atoms and through the amino group with Si adatoms, which enables the remaining free functional groups to selectively bond with different incoming molecules. Instead of the “universal” three-stage growth found for cysteine adsorption on a pristine Si(111)7×7 surface, we observe the two-stage growth of cysteine on the supported gold honeycomb nanonetwork (i.e., without a transitional layer), similar to that found on a gold single-crystal surface. The formation of the ultrathin gold-silicide layer (honeycomb) has effectively transformed the semiconductor surface to a metal-like surface.

A CE-FL based method for real-time detection of in-capillary self-assembly of the nanoconjugates of polycysteine ligand and quantum dots

Small molecules with free thiol groups always show high binding affinity to quantum dots (QDs). However, it is still highly challenging to detect the binding capacity between thiol-containing molecules and QDs inside a capillary. To conquer this limitation, a capillary electrophoresis with fluorescence detection (CE-FL) based assay was proposed and established to investigate the binding capacity between QDs and a poly-thiolated peptide (ATTO 590-DDSSGGCCPGCC, ATTO-C4). Interestingly, the results showed that interval time had a great influence on QDs and ATTO-C4 self-assembly, which can be attributed to longer interval time benefitting the binding of QDs to ATTO-C4. The stability assays on ATTO-C4-QD assembly indicated that high concentration of imidazole or GSH had a high capability of competing with the bound ATTO-C4, evidenced by dramatically dropping of S625/S565 ratio from 0.78 to 0.30 or 0.29. Therefore, all these results above suggested that this novel CE-FL based detection assay could be successfully applied to the binding studies between QDs and thiol-containing biomolecules.

Facile Fabrication of a Modular "Catch and Release" Hydrogel Interface: Harnessing Thiol-Disulfide Exchange for Reversible Protein Capture and Cell Attachment.

Surfaces engineered to "specifically capture" and "release on demand" analytes ranging from biomolecules to cells find niche applications in areas such as diagnostics and detection. Utilization of a disulfide-based linker as a building block allows fabrication of a novel hydrogel-based platform that incorporates a "catch and release" attribute. Hydrogels incorporating pyridyl disulfide groups as thiol-reactive handles were prepared by photopolymerization in the presence of a poly(ethylene glycol) (PEG)-based cross-linker. A range of bulk and micropatterned hydrogels with varying amounts of the reactive group were prepared using PEG-based monomers with different chain lengths. Thiol-containing molecules were conjugated to these hydrogels through the thiol-disulfide exchange reaction under ambient conditions with high efficiencies, as determined by UV-vis spectroscopy. Facile conjugation of a thiol-containing fluorescent dye, namely 4,4-difluoro-1,3,5,7-tetramethyl-8-[(10-mercapto)]-4-bora-3 a,4 a-diaza- s-indacene, was demonstrated, followed by its effective cleavage in the presence of dithiothreitol (DTT), a thiol-containing disulfide-reducing agent. Conjugation of a biotin-containing ligand onto the hydrogels allowed specific binding of protein extravidin when exposed to a mixture of extravidin and bovine serum albumin. The bound protein could be released from the hydrogel by simple exposure to a DTT solution. Likewise, hydrogels modified with a cell-adhesive peptide unit containing the RGD sequence acted as favorable substrates for cellular attachment. Incubation of these cell-attached hydrogel surfaces in a DTT-containing solution leads to facile detachment of cells from the surfaces, while retaining a high level of cell viability. It can be envisioned that the benign nature of these hydrogels, their facile fabrication, and modular functionalization will make them attractive platforms for many applications.

Micro-patterns on nanocellulose films and paper by photo-induced thiol–yne click coupling: a facile method toward wetting with spatial resolution

We report a facile approach to tailor the wettability of ligno-cellulosic substrates via photo-induced thiol–yne click coupling. First, cellulosic surfaces were functionalized with 4-pentynoic acid to introduce terminal alkyne moieties for the subsequent photo-induced coupling in heterogeneous phase. Next, the (primed) surfaces were reacted with various thiol-containing molecules to systematically tailor the surface energy. Finally, the method was applied to nanocellulose films and paper to develop micro-patterned surfaces via UV lithography, endowing the substrates with thin hydrophilic channels (~ 250 μm thickness) and hydrophobic boundaries between neighboring water droplets, as small as 100 μm in width. Overall, we propose thiol-click as a facile method toward spatially-resolved wetting that enables paper-based electronics in smart labels and point-of-care bioplatforms.

An ortho-aldehyde modified probe to image thiols in living cells with enhanced selectivity

Developing fluorescent probes to image thiols in the living system may provide powerful tools to study the functions of thiol-containing biological molecules. In this study, we report the design and evaluation of a novel turn-on fluorescent probe NQNO for selective detection of thiols in living cells. By introducing an ortho-aldehyde group to NNO, a conventional compound representing a class of thiol-imaging strategy, we obtained NQNO with enhanced selectivity for thiols over the major interferent hydrogen sulfide (H2S). NQNO could be applied in phosphate-buffered saline (PBS), where the efficacy of NNO was usually weakened. Notably, NQNO demonstrated solid performance in imaging endogenous thiols in living cells without exerting cytotoxicity. In summary, NQNO has the potential to serve as a safe, sensitive and effective fluorescent probe for thiol imaging in biological systems.

Functionalization of Reduced Graphene Oxide via Thiol-Maleimide "Click" Chemistry: Facile Fabrication of Targeted Drug Delivery Vehicles.

Materials based on reduced graphene oxide (rGO) have shown to be amenable to noncovalent functionalization through hydrophobic interactions. The scaffold, however, does not provide sufficient covalent linkage given the low number of reactive carboxyl and alcohol groups typically available on the rGO. The integration of clickable groups, particularly the ones that can undergo efficient conjugation without any metal catalyst, would allow facile functionalization of these materials. This study reports on the noncovalent association of a maleimide-containing catechol (dopa-MAL) surface anchor onto the rGO. Thiol-maleimide chemistry allows thereafter the facile attachment of thiol-containing molecules under ambient metal-free conditions. Although the attachment of glutathione and 6-(ferrocenyl)hexanethiol was used as model thiols, the attachment of a cancer cell targeting cyclic peptide, c(RGDfC), opened the possibility of using the dopa-MAL-modified rGO as a targeted drug delivery system for doxorubicin (DOX). Although free DOX showed to be more effective at killing the human cervical cancer cells (HeLa) over human breast adenocarcinoma cancer cells (MDA-MB-231), the DOX-loaded rGO/dopa-MAL-c (RGDfC) nanostructure showed an opposite effect being notably more effective at targeting and killing the MDA-MB-231 cells. The effect is enhanced upon laser irradiation for 10 min at 2 W cm-2. The facile fabrication and functionalization to readily obtain a functional material in a modular fashion make this clickable-rGO construct an attractive platform for various applications.

Oxidation of the drug tiopronin by Cerium(IV) in perchloric acid media: Kinetic and mechanistic analyses

Although several analytical methods based on the Ce(IV) oxidations were developed for determinations of the drug tiopronin (MPG) and some biothiols, the kinetic and mechanistic aspects of oxidations of the thiol-containing molecules by Ce(IV) were poorly deciphered if not all. The oxidation of MPG by Ce(IV) has thus been characterized kinetically in perchloric acid media in this work. The oxidation reaction follows overall second-order kinetics: -d[Ce(IV)]tot/dt=k′[MPG]tot[Ce(IV)]tot, where k′ stands for the observed second-order rate constant and [Ce(IV)]tot and [MPG]tot pertain to the total concentrations of Ce(IV) and MPG, respectively. The relation between k′ and [H+] has been established in the region of 0.030M≤[H+]≤2.00M. Several additional reaction features are revealed by the rapid scan spectra, product identification and stoichiometric study. All these features are rationalized by a proposed reaction mechanism which involves Ce4+, Ce(OH)3+, and Ce(OH)22+ attacking on the sulfur atom of MPG in parallel and forming the rate-determining steps. These steps are followed by up to seven fast reactions. Rate constants of the rate-determining steps have been derived showing a reactivity trend: Ce4+>Ce(OH)3+>Ce(OH)22+. This trend, being observed for the first time in this work, suggests an outer-sphere electron transfer taking place in the rate-determining steps, which is strongly bolstered by the dependence of the Ce(IV)/Ce(III) redox potential on [H+] measured previously. Our kinetic and mechanistic analyses indicate that a rather complex reaction mechanism is operating behind the simple second-order kinetics.

Activated carbon-plasticised agarose composite films for the adsorption of thiol as a model of wound malodour.

Conditions such as diabetes, cardiovascular disease and long-term immobilisation can precipitate the development of chronic dermal ulcers. Such wounds are associated with inflammation and bacterial contamination which in turn can lead to the liberation of offensive odours that cause patient embarrassment and, in some instances, social isolation. Activated carbon-containing dressings have been used to manage the odours from such wounds. However, these can be bulky and can become fouled by wound exudate. Agarose is a natural polysaccharide derived from seaweed that forms brittle free-standing films that can be made pliable by addition of a plasticiser. In this study, activated carbon-containing plasticised agarose films were evaluated for their ability to sequester thiol-containing molecules from solution and the gaseous phase. The water vapour transmission rate was also evaluated to determine the potential breathability of these films should they be considered for application to the skin. It was found that the adsorption of thiols was directly proportional to the activated carbon content of the films. Water vapour was found to pass relatively freely through the films indicating that sweat-induced tissue maceration would be unlikely to occur if applied clinically. In conclusion, activated carbon-containing plasticised agarose films have some potential in the sequestration of malodourous molecules such as those liberated from chronic dermal wounds.

Microwave-Assisted thiol-ene click chemistry of carbon nanoforms

Carbon nanoforms (CNFs, including graphene, carbon nanotube and fullerene) were functionalized via microwave-assisted thiol-ene click chemistry. Different functional CNFs with −COOH, −NH2, −NH3Cl,-Si(OCH3)3, alkyl and furyl groups were obtained and characterized by XPS, EDS, TGA, Raman spectroscopy and MALDI-TOF MS. Microwave was much more efficient to promote reactions than traditional thermal method. XPS confirmed the binding energy of C-S-C (163.3ev) the modified CNFs. Raman spectroscopy showed increasing ID/IG and AD/AG of graphene and CNT after thiol-ene addition reaction. The result of MALDI-TOF MS indicated that the thiol-containing molecules were attached on fullerene. All these results indicated the successful thiol-ene click reactions between CNFs and thiol-containing molecules under microwave. TGA analysis results showed the mass loss of the modified CNFs, which provided that AIBN and 3-merlaptopropionic acid were the most efficient initiator and monomer, respectively. In summary, the microwave-assisted thiol-ene click reaction provided a powerful chemical tool for the preparation of functional CNFs materials.

N-Acetyl-l-Cysteine Protects Astrocytes against Proteotoxicity without Recourse to Glutathione.

N-acetyl-l-cysteine (NAC) exhibits protective properties in brain injury models and has undergone a number of clinical trials. Most studies of NAC have focused on neurons. However, neuroprotection may be complemented by the protection of astrocytes because healthier astrocytes can better support the viability of neurons. Here, we show that NAC can protect astrocytes against protein misfolding stress (proteotoxicity), the hallmark of neurodegenerative disorders. Although NAC is thought to be a glutathione precursor, NAC protected primary astrocytes from the toxicity of the proteasome inhibitor MG132 without eliciting any increase in glutathione. Furthermore, glutathione depletion failed to attenuate the protective effects of NAC. MG132 elicited a robust increase in the folding chaperone heat shock protein 70 (Hsp70), and NAC mitigated this effect. Nevertheless, three independent inhibitors of Hsp70 function ablated the protective effects of NAC, suggesting that NAC may help preserve Hsp70 chaperone activity and improve protein quality control without need for Hsp70 induction. Consistent with this view, NAC abolished an increase in ubiquitinated proteins in MG132-treated astrocytes. However, NAC did not affect the loss of proteasome activity in response to MG132, demonstrating that it boosted protein homeostasis and cell viability without directly interfering with the efficacy of this proteasome inhibitor. The thiol-containing molecules l-cysteine and d-cysteine both mimicked the protective effects of NAC, whereas the thiol-lacking molecule N-acetyl-S-methyl-l-cysteine failed to exert protection or blunt the rise in ubiquitinated proteins. Collectively, these findings suggest that the thiol group in NAC is required for its effects on glial viability and protein quality control.

Exploring the C^N^C theme: Synthesis and biological properties of tridentate cyclometalated gold(III) complexes

A family of cyclometalated Au(III) complexes featuring a tridentate C^N^C scaffold has been synthesized and characterized. Microwave assisted synthesis of the ligands has also been exploited and optimized. The biological properties of the thus formed compounds have been studied in cancer cells and demonstrate generally moderate antiproliferative effects. Initial mechanistic insights have also been gained on the gold complex [Au(C^N^C)(GluS)] (3), and support the idea that the thioredoxin system may be a target for this family of compounds together with other relevant intracellular thiol-containing molecules.

Competitive reactions among glutathione, cisplatin and copper-phenanthroline complexes

A large number of cancers are treated with cisplatin (CDDP). However, its use is limited by drug resistance, which is often related to intracellular levels of thiol-containing molecules such as glutathione (GSH). The role of GSH in cisplatin-resistant cancer cells is still unclear. GSH may form adducts with CDDP which results in the deactivation of the drug, and, actually, a high intracellular level of GSH was observed in some cisplatin-resistant cancers. To overcome drug resistance, CDDP is often administered in combination with one or more drugs to exploit a possible synergistic effect. In previous studies, we observed that the sensitivity to CDDP of leukemic and ovarian cisplatin-resistant cancer cells was restored in the presence of [Cu(phen)2(H2O)](ClO4)2 (C0) (phen is 1,10-phenathroline). In order to clarify the possible interactions between GSH and CDDP, the reactivity and competitive reactions among CDDP, C0 and GSH in binary and ternary mixtures were studied. The investigation was extended also to [Cu(phen)(H2O)2(ClO4)2] (C10) and GSSG, the oxidized form of GSH. It was observed that CDDP was able to react with the studied copper complexes and with GSH or GSSG. However, in mixtures containing CDDP, GSH or GSSG and C0 or C10, only copper-glutathione complexes were detected, while no platinum-glutathione adducts were found.

Engineering of Surface Chemistry for Enhanced Sensitivity in Nanoporous Interferometric Sensing Platforms.

We explore new approaches to engineering the surface chemistry of interferometric sensing platforms based on nanoporous anodic alumina (NAA) and reflectometric interference spectroscopy (RIfS). Two surface engineering strategies are presented, namely (i) selective chemical functionalization of the inner surface of NAA pores with amine-terminated thiol molecules and (ii) selective chemical functionalization of the top surface of NAA with dithiol molecules. The strong molecular interaction of Au3+ ions with thiol-containing functional molecules of alkane chain or peptide character provides a model sensing system with which to assess the sensitivity of these NAA platforms by both molecular feature and surface engineering. Changes in the effective optical thickness of the functionalized NAA photonic films (i.e., sensing principle), in response to gold ions, are monitored in real-time by RIfS. 6-Amino-1-hexanethiol (inner surface) and 1,6-hexanedithiol (top surface), the most sensitive functional molecules from approaches i and ii, respectively, were combined into a third sensing strategy whereby the NAA platforms are functionalized on both the top and inner surfaces concurrently. Engineering of the surface according to this approach resulted in an additive enhancement in sensitivity of up to 5-fold compared to previously reported systems. This study advances the rational engineering of surface chemistry for interferometric sensing on nanoporous platforms with potential applications for real-time monitoring of multiple analytes in dynamic environments.