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Visualizing the presence and distribution of multiple specific molecular markers within a tumor can reveal the composition of its microenvironment, inform diagnosis, stratify patients, and guide treatment. Raman imaging with multiple molecularly-targeted surface enhanced Raman scattering (SERS) nanoprobes could help investigate emerging cancer treatments preclinically or enable personalized treatment assessment. Here, we report a comprehensive strategy for multiplexed imaging using SERS nanoprobes and machine learning (ML) to monitor the early effects of immune checkpoint blockade (ICB) in tumor-bearing mice. We used antibody-functionalized SERS nanoprobes to visualize 7 + 1 immunotherapy-related targets simultaneously. The multiplexed images were spectrally resolved and then spatially segmented into superpixels based on the unmixed signals. The superpixels were used to train ML models, leading to the successful classification of mice into treated and untreated groups, and identifying tumor regions with variable responses to treatment. This method may help predict treatment efficacy in tumors and identify areas of tumor variability and therapy resistance.

Rationale: Surface enhanced Raman scattering (SERS) is proving to be a useful tool for biomedical imaging. However, this imaging technique can suffer from poor signal-to-noise ratio, as the complexity of biological tissues can lead to overlapping of Raman bands from tissues and the Raman reporter molecule utilized. Methods: Herein we describe the synthesis of triple bond containing Raman reporters that scatter light in the biological silent window, between 1750 cm -1 and 2750 cm -1 . Results: Our SERS nanoprobes are comprised of uniquely designed Raman reporters containing either alkyne- or cyano-functional groups, enabling them to be readily distinguished from background biological tissue. Conclusion: We identify promising candidates that eventually can be moved forward as Raman reporters in SERS nanoparticles for highly specific contrast-enhanced Raman-based disease or analyte detection in biological applications., Competing Interests: Competing Interests: Stefan Harmsen is listed as inventor on several patents related to the SERS technology used in this work. Sanjiv Sam Gambhir holds the original patent on the use of SERS in living subjects., (© The author(s).)

Acute graft-versus-host-disease (GVHD), limits the use of hematopoietic cell transplant (HCT) to treat a variety of malignancies. Any new therapeutic approach must satisfy three requirements: 1) Prevent GVHD, 2) Maintain anti-pathogen immunity, and 3) Maintain anti-tumor immunity. In prior studies we have shown that the selective photosensitizer 2-Se-Cl eliminates highly alloreactive lymphocytes from the graft prior to HCT preventing GVHD and that antiviral immune responses were preserved following incubation with 2-Se-Cl. In this report, we investigated whether 2-Se-Cl treatment preserves antitumor immunity, and then used high dimensional flow cytometry to identify the determinants of successful immune reconstitution. Donor C57BL/6 splenocytes were cocultured for 4 days with irradiated BALB/c splenocytes and then exposed to 2-Se-Cl. Photodepletion (PD)-treated splenocytes were then infused into lethally irradiated BALB/c mice inoculated with A20 leukemia/lymphoma cells. Recipient mice that received PD-treated splenocytes survived > 100 days without evidence of GVHD or leukemia. In contrast, mice that did not receive PD-treated cells at time of HCT died of leukemia progression. Multiparameter flow cytometry of cytokines and surface markers on peripheral blood samples 15 days after HCT demonstrated unique patterns of immune reconstitution. We found that before clinical disease onset GVHD was marked by functionally exhausted T cells, while tumor clearance and long-term survival were associated with an expansion of polyfunctional T cells, monocytes, and DCs early after transplantation. Taken together these results demonstrate that 2-Se-Cl photodepletion is a new treatment that can facilitate HCT by preventing GVHD while preserving antiviral and anti-tumor immunity., Competing Interests: The authors have declared that no competing interests exist.

Chalcogenopyrylium monomethine (CGPM) dyes represent a class of environmentally activated singlet oxygen generators with applications in photodynamic therapy (PDT) and photoassisted chemotherapy (PACT). Upon binding to genomic material, the dyes are presumed to rigidify, allowing for intersystem crossing to outcompete excited state deactivation by internal conversion. This results in large triplet yields and hence large singlet oxygen yields. To understand the nature of the internal conversion process that controls the activity of the dyes, femtosecond transient absorption experiments were performed on a series of S-, Se-, and Te-substituted CGPM dyes. For S- and Se-substituted species in methanol, rapid internal conversion from the singlet excited state, S 1 , occurs in ∼5 ps, deactivating the optically active excited state. The internal conversion produces a distorted ground-state species that returns to its equilibrium structure in ∼20 ps. For Te-substituted species, the internal conversion competes with rapid intersystem crossing to the lowest triplet state, T 1 , which occurs with a ∼ 100 ps time constant in methanol. In more viscous methanol/glycerol mixtures, the internal conversion to the ground state slows by 2 orders of magnitude, occurring in 500-600 ps. For Se- and Te-substituted species in viscous environments, the slower internal conversion rate allows a larger triplet yield. Using femtosecond stimulated Raman spectroscopy (FSRS) and time-dependent density functional theory (TD-DFT), the internal conversion is determined to occur by twisting of the pyrylium rings about the monomethine bridge. Evolution from the distorted ground state occurs by twisting back to the S 0 equilibrium structure. The environmentally dependent photoactivity of CGPM dyes is discussed in the context of PDT and PACT applications.

Laboratory evaluation of antifouling coatings is underpinned by settlement studies with specific fouling organisms. Established methods provide insight into the likelihood of failure of a particular coating system, but can neglect the process of surface selection that often precedes attachment. The present approach for quantifying the exploratory behaviour of barnacle cypris larvae suggested that inspection behaviour can be a rapid and predictive proxy for settlement. Two series of xerogels with comparable total surface energy, but different dispersive and polar components, were evaluated. Settlement assays with three-day-old cyprids of Balanus improvisus demonstrated that while attachment was not linked directly to dispersive free energy, the composition of the xerogel was nevertheless significant. Behavioural analysis provided insight into the mechanism of surface rejection. In the case of a 50:50 PH/TEOS (phenyltriethoxysilane-based) xerogel vs a 50:50 TFP/TEOS (3,3,3-trifluoropropyltrimethoxysilane-based) xerogel, wide-searching behaviour was absent on the former.

The ability to probe through barriers and tissue non-invasively is an urgent unmet need in both the security and biomedical imaging fields. Surface enhanced Raman spectroscopy (SERS) has been shown to yield superior enhancement in signal over conventional Raman techniques. Furthermore, by utilising a resonant Raman reporter to produce surface enhanced resonance Raman spectroscopy (SERRS), even greater enhancement in chemical signal can be generated. Here we show the benefit of using red-shifted chalcogenpyrylium based Raman reporters for probing through large thicknesses of plastic and tissue barriers using a conventional Raman instrument. In addition, the benefit of using a resonant Raman reporter for superior levels of through barrier detection is demonstrated, and we aim to show the advantage of using resonant nanotags in combination with conventional Raman spectroscopy to probe through plastic and tissue barriers. Raman signals were collected from SERRS active nanotags through plastic thicknesses of up to 20 mm, as well as the detection of the same SERRS nanotags through up to 10 mm of tissue sections using a handheld conventional Raman spectrometer. The ability to detect SERRS-active nanotags taken up into ex vivo tumour models known as multicellular tumour spheroids (MTS), through depths of 5 mm of tissue is also shown. The advantages of applying multivariate analysis for through barrier detection when discriminating analytes with similar spectral features as the barrier is also clearly demonstrated. To the best of our knowledge, this is the first report of the assessment of the maximum level of through barrier detection using a conventional handheld Raman instrument for SERS applications as well as demonstration of the power of resonant nanotags for probing through barriers using conventional Raman spectroscopy.

Resonant chalcogenpyrylium nanotags demonstrate an exceptional surface enhanced Raman scattering (SERS) performance for use in SORS applications. Using surface enhanced spatially offset Raman spectroscopy (SESORS), nanotags modified with a chalcogenpyrylium dye were observed at concentrations as low as 1 pM through 5 mm of tissue. Calculated limits of detection suggest that these SERS nanotags can be detected at 104 fM using surface enhanced spatially offset resonance Raman scattering (SESORRS) demonstrating their potential for in vivo applications.

Through utilizing the depth penetration capabilities of SESORS, multiplexed imaging and classification of three singleplex nanotags and a triplex of nanotags within breast cancer tumour models is reported for the first time through depths of 10 mm using a handheld SORS instrument.

Oligonucleotide functionalised metallic nanoparticles (MNPs) have been shown to be an effective tool in the detection of disease-specific DNA and have been employed in a number of diagnostic assays. The MNPs are also capable of facilitating surface enhanced Raman scattering (SERS) enabling detection to become highly sensitive. Herein we demonstrate the expansion of the range of specific SERS-active oligonucleotide MNPs through the use of 12 new Raman-active monomethine and trimethine chalcogenopyrylium and benzochalcogenopyrylium derivatives. This has resulted in an increased ability to carry out multiplexed analysis beyond the current small pool of resonant and non-resonant Raman active molecules, that have been used with oligonucleotide functionalised nanoparticles. Each dye examined here contains a variation of sulphur and selenium atoms in the heterocyclic core, together with phenyl, 2-thienyl, or 2-selenophenyl substituents on the 2,2',6, and 6' positions of the chalcogenopyrylium dyes and 2 and 2' positions of the benzochalcogenopyrylium dyes. The intensity of SERS obtained from each dye upon conjugate hybridisation with a complementary single stranded piece of DNA was explored. Differing concentrations of each dye (1000, 3000, 5000 and 7000 equivalents per NP-DNA conjugate) were used to understand the effects of Raman reporter coating on the overall Raman intensity. It was discovered that dye concentration did not affect the target/control ratio, which remained relatively constant throughout and that a lower concentration of Raman reporter was favourable in order to avoid NP instability. A relationship between the dye structure and SERS intensity was discovered, leaving scope for future development of specific dyes containing substituents favourable for discrimination in a multiplex by SERS. Methine dyes containing S and Se in the backbone and at least 2 phenyls as substituents give the highest SERS signal following DNA-induced aggregation. Principal component analysis (PCA) was performed on the data to show differentiation between the dye classes and highlight possible future multiplexing capabilities of the 12 investigated dyes., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In order to improve patient survival and reduce the amount of unnecessary and traumatic biopsies, non-invasive detection of cancerous tumours is of imperative and urgent need. Multicellular tumour spheroids (MTS) can be used as an ex vivo cancer tumour model, to model in vivo nanoparticle (NP) uptake by the enhanced permeability and retention (EPR) effect. Surface enhanced spatially offset Raman spectroscopy (SESORS) combines both surface enhanced Raman spectroscopy (SERS) and spatially offset Raman spectroscopy (SORS) to yield enhanced Raman signals at much greater sub-surface levels. By utilizing a reporter that has an electronic transition in resonance with the laser frequency, surface enhanced resonance Raman scattering (SERRS) yields even greater enhancement in Raman signal. Using a handheld SORS spectrometer with back scattering optics, we demonstrate the detection of live breast cancer 3D MTS containing SERRS active NPs through 15 mm of porcine tissue. False color 2D heat intensity maps were used to determine tumour model location. In addition, we demonstrate the tracking of SERRS-active NPs through porcine tissue to depths of up to 25 mm. This unprecedented performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters to demonstrate the novel technique of surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) for the first time. Our results demonstrate a significant step forward in the ability to detect vibrational fingerprints from a tumour model at depth through tissue. Such an approach offers significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement.

Multivariate analyses were used to investigate the influence of selected surface properties (Owens-Wendt surface energy and its dispersive and polar components, static water contact angle, conceptual sign of the surface charge, zeta potentials) on the attachment patterns of five biofouling organisms (Amphibalanus amphitrite, Amphibalanus improvisus, Bugula neritina, Ulva linza, and Navicula incerta) to better understand what surface properties drive attachment across multiple fouling organisms. A library of ten xerogel coatings and a glass standard provided a range of values for the selected surface properties to compare to biofouling attachment patterns. Results from the surface characterization and biological assays were analyzed separately and in combination using multivariate statistical methods. Principal coordinate analysis of the surface property characterization and the biological assays resulted in different groupings of the xerogel coatings. In particular, the biofouling organisms were able to distinguish four coatings that were not distinguishable by the surface properties of this study. The authors used canonical analysis of principal coordinates (CAP) to identify surface properties governing attachment across all five biofouling species. The CAP pointed to surface energy and surface charge as important drivers of patterns in biological attachment, but also suggested that differentiation of the surfaces was influenced to a comparable or greater extent by the dispersive component of surface energy.

This is the first report of the use of a hand-held 1064 nm Raman spectrometer combined with red-shifted surface-enhanced Raman scattering (SERS) nanotags to provide an unprecedented performance in the short-wave infrared (SWIR) region. A library consisting of 17 chalcogenopyrylium nanotags produce extraordinary SERS responses with femtomolar detection limits being obtained using the portable instrument. This is well beyond previous SERS detection limits at this far red-shifted wavelength and opens up new options for SERS sensors in the SWIR region of the electromagnetic spectrum (between 950 and 1700 nm)., Competing Interests: We declare we have no competing interests.

Intrinsic optical properties of several rhodamine cations were probed by measuring their dispersed fluorescence spectra in vacuo. Three different rhodamine structures were investigated, each with four different chalcogen heteroatoms. Fluorescence band maxima were blue-shifted by between 0.15 and 0.20 eV (1200-1600 cm -1 ) relative to previous solution-phase measurements. Trends in emission wavelengths and fluorescence quantum yields previously measured in solution are generally reproduced in the gas phase, confirming the intrinsic nature of these effects. One important exception is gas-phase brightness of the Texas Red analogues, which is significantly higher than the other rhodamine structures studied, despite having similar fluorescence quantum yields in solution. These results expand the library of fluorophores for which gas-phase photophysical data is available, and will aid in the design of experiments utilizing gas-phase structural biology methods such as Förster resonance energy transfer.

Although rhodamine dyes have been extensively studied for a variety of applications, many details of their photophysics are not yet fully understood, including the possible presence of a charge separated electronic state lying near the optically active excited singlet state and the role of twisting substituent groups in excited-state quenching. To address this, a large library of rhodamine dyes was studied in which the chalcogen is varied from O, to S and Se and the aryl group is either absent (in the pyronin series) or is a phenyl or thienyl substituent. Through an analysis of steady-state absorption spectroscopy, electrochemistry, X-ray crystallography, and quantum mechanical calculations, we show that the lowest unoccupied molecular orbital (LUMO) energy decreases in the O → S → Se series and when a phenyl or thienyl substituent is added. The reduction of the LUMO energy is larger for thienyl species in which the aromatic group has increased torsional flexibility. Excited state lifetimes and fluorescence quantum yields of these dyes in a high and low polarity solvent reveal dramatically different photophysics between chromophores with phenyl and thienyl substituents, due to a combination of torsional and inductive effects. In the pyronin and phenyl-substituted species, non-radiative decay can occur through an amine-to-xanthylium core charge separated state that is stabilized in a highly polar environment. In the thienyl derivatives, a lower energy excited state, which we term S' 1 , is accessed from S 1 via rotation of the aryl group and the excited state population rapidly equilibrates between S 1 and S' 1 in 6-30 ps. Preliminary photochemical hydrogen production data display the potential application of the thienyl derivatives for conversion of solar energy.

Surface patterns over multiple length scales are known to influence various biological processes. Here we report the synthesis and characterization of new, two-component xerogel thin films derived from carboxyethylsilanetriol (COE) and tetraethoxysilane (TEOS). Atomic force microscopy (AFM) reveals films surface with branched and hyper branched architectures that are ∼2 to 30 μm in diameter, that extend ∼3 to 1300 nm above the film base plane with surface densities that range from 2 to 77% surface area coverage. Colocalized AFM and Raman spectroscopy show that these branched structures are COE-rich domains, which are slightly stiffer (as shown from phase AFM imaging) and exhibit lower capacitive force in comparison with film base plane. Raman mapping reveals there are also discrete domains (≤300 nm in diameter) that are rich in COE dimers and densified TEOS, which do not appear to correspond with any surface structure seen by AFM.

Mixed titania/silica xerogels were prepared using titanium tetraisopropoxide (TTIP) and tetraethoxy orthosilicate (TEOS). Xerogel properties were modified by incorporating n-octyltriethoxysilane (C8). The xerogels catalyze the oxidation of bromide and chloride with hydrogen peroxide (H2O2) to produce hypohalous acids at pH 7 and pH 8. The antifouling/ fouling-release performance of a TTIP/C8/TEOS xerogel in the presence and absence of H2O2 was evaluated for the settlement of zoospores of the marine alga Ulva linza and for the removal of sporelings (young plants). In the absence of H2O2, differences in the settlement of zoospores and removal of sporelings were not significant relative to a titanium-free C8/TEOS xerogel. Addition of H2O2 gave a significant reduction in zoospore settlement and sporeling removal relative to the C8/TEOS xerogel and relative to peroxide-free conditions. The impact of TTIP on xerogel characteristics was evaluated by comprehensive contact angle analysis, scanning electron microscopy, and X-ray photoelectron spectroscopy.

Extracorporeal photopheresis (ECP) has been used successfully in the treatment of erythrodermic cutaneous T cell lymphoma (CTCL), and other T cell-mediated disorders. Not all patients obtain a significant or durable response from ECP. The design of a selective photosensitizer that spares desirable lymphocytes while targeting malignant T cells may promote cytotoxic T cell responses and improve outcomes after ECP. A series of selenorhodamines built with variations of the Texas red core targeted the mitochondria of malignant T cells, were phototoxic to malignant T cells presumably via their ability to generate singlet oxygen, and were transported by P-glycoprotein (P-gp). To determine the selectivity of the photosensitizers in the ECP milieu, staphylococcal enterotoxin B (SEB)-stimulated and non-stimulated human lymphocytes were combined with HUT-78 cells (a CTCL) to simulate ECP. The amide-containing analogues of the selenorhodamines were transported more rapidly than the thioamide analogues in monolayers of MDCKII-MDR1 cells and, consequently, were extruded more rapidly from P-gp-expressing T cells than the corresponding thioamide analogues. Selenorhodamine 6 with the Texas red core and a piperidylamide functionality was phototoxic to >90% of malignant T cells while sparing >60% of both stimulated and non-stimulated T cells. In the resting T cells, (63±7)% of the CD4+ T cell compartment, and (78±2.5)% of the CD8+ cytotoxic T cell population were preserved, resulting in an enrichment of healthy and cytotoxic T cells after photodepletion., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Extended thio- and selenorhodamines with a linear or angular fused benzo group were prepared. The absorption maxima for these compounds fell between 640 and 700nm. The extended rhodamines were evaluated for their potential as photosensitizers for photodynamic therapy in Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 and HUT-78 cells. The angular extended rhodamines were effective photosensitizers toward Colo-26 cells with 1.0Jcm(-2) laser light delivered at λmax±2nm with values of EC50 of (2.8±0.4)×10(-7)M for sulfur-containing analogue 6-S and (6.4±0.4)×10(-8)M for selenium-containing analogue 6-Se. The linear extended rhodamines were effective photosensitizers toward Colo-26 cells with 5 and 10Jcm(-2) of broad-band light (EC50's⩽2.4×10(-7)M)., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

T lymphocytes play a central role in many human immunologic disorders, including autoimmune and alloimmune diseases. In hematopoietic stem cell transplantation, acute graft-versus-host-disease (GVHD) is caused by an attack on the recipient's tissues from donor allogeneic T cells. Selectively depleting GVHD-causing cells prior to transplant may prevent GVHD. In this study, we evaluated 24 chalcogenorhodamine photosensitizers for their ability to selectively deplete reactive T lymphocytes and identified the photosensitizer 2-Se-Cl, which accumulates in stimulated T cells in proportion to oxidative phosphorylation. The photosensitizer is also a potent stimulator of P-glycoprotein (P-gp). Enhanced P-gp activity promotes the efficient removal of photosensitizer not sequestered in mitochondria and protects resting lymphocytes that are essential for antipathogen and antitumor responses. To evaluate the selective depletion of alloimmune responses, donor C57BL/6 splenocytes were cocultured for 5 d with irradiated BALB/c splenocytes and then photodepleted (PD). PD-treated splenocytes were infused into lethally irradiated BALB/c (same-party) or C3H/HeJ (third-party) mice. Same-party mice that received PD-treated splenocytes at the time of transplant lived 100 d without evidence of GVHD. In contrast, all mice that received untreated primed splenocytes and third-party mice that received PD-treated splenocytes died of lethal GVHD. To evaluate the preservation of antiviral immune responses, acute lymphocytic choriomeningitis virus infection was used. After photodepletion, expansion of Ag-specific naive CD8(+) T cells and viral clearance remained fully intact. The high selectivity of this novel photosensitizer may have broad applications and provide alternative treatment options for patients with T lymphocyte-mediated diseases., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Chalcogenopyrylium nanotags demonstrate an unprecedented SERS performance with a retina safe, 1550 nm laser excitation. These unique nanotags consisting of chalcogenopyrylium dyes and 100 nm gold nanoparticles produce exceptional SERS signals with picomolar detection limits obtained at this extremely red-shifted and eye-safe laser excitation.

Infrared surface enhanced Raman scattering (SERS) is an attractive technique for the in situ detection of nanoprobes in biological samples due to the greater depth of penetration and reduced interference compared to SERS in the visible region. A key challenge is to understand the surface layer formed in suspension when a specific label is added to the SERS substrate in aqueous suspension. SERS taken at different wavelengths, theoretical calculations, and surface-selective sum frequency generation vibrational spectroscopy (SFG-VS) were used to define the surface orientation and manner of attachment of a new class of infrared SERS labels with a thiopyrylium core and four pendant 2-selenophenyl rings. Hollow gold nanospheres (HGNs) were used as the enhancing substrate and two distinct types of SERS spectra were obtained. With excitation close to resonance with both the near infrared electronic transition in the label (max 826 nm) and the plasmon resonance maximum (690 nm), surface enhanced resonance Raman scattering (SERRS) was obtained. SERRS indicates that the major axis of the core is near to perpendicular to the surface plane and SFG-VS obtained from a dried gold film gave a similar orientation with the major axis at an angle 64-85° from the surface plane. Longer excitation wavelengths give SERS with little or no molecular resonance contribution and new vibrations appeared with significant displacements between the thiopyrylium core and the pendant selenophene rings. Analysis using calculated spectra with one or two rings rotated indicates that two rings on one end are rotated towards the metal surface to give an arrangement of two selenium and one sulphur atoms directly facing the gold structure. The spectra, together with a space filled model, indicate that the molecule is strongly adsorbed to the surface through the selenium and sulphur atoms in an arrangement which will facilitate layer formation.

A library of six selenorhodamine dyes (4-Se-9-Se) were synthesized, characterized, and evaluated as photosensitizers of TiO2 in dye-sensitized solar cells (DSSCs). The dyes were constructed around either a bis(julolidyl)- or bis(half-julolidyl)-modified selenoxanthylium core functionalized at the 9-position with a thienyl group bearing a carboxylic, hydroxamic, or phosphonic acid for attachment to TiO2. Absorption bands of solvated dyes 4-Se-9-Se were red-shifted relative to the dimethylamino analogues. The dyes adsorbed to TiO2 as mixtures of monomeric and H-aggregated dyes, which exhibited broadened absorption spectra and increased light-harvesting efficiencies relative to the solvated monomeric dyes. Carboxylic acid-bearing dyes 4-Se and 7-Se initially exhibited the highest incident photon-to-current efficiencies (IPCEs) of 65-80% under monochromatic illumination, but the dyes desorbed rapidly from TiO2 into solutions of HCl (0.1 M) in a CH3CN:H2O mixed solvent (120:1 v:v). The hydroxamic acid- and phosphonic acid-bearing dyes 5-Se, 6-Se, 8-Se, and 9-Se exhibited lower IPCEs (49-65%) immediately after preparation of DSSCs; however, the dyes were vastly more inert on TiO2, and IPCEs decreased only minimally with successive measurements under constant illumination. Power-conversion efficiencies (PCEs) of the selenorhodamine-derived DSSCs were less than 1%, probably due to inefficient regeneration of the dyes following electron injection. For a given anchoring group, the bis(half-julolidyl) dyes exhibited higher open-circuit photovoltages and PCEs than the corresponding bis(julolidyl) dyes. The hydroxamic acid- and phosphonic acid-bearing dyes are intriguing photosensitizers of TiO2 in light of their aggregation-induced spectral broadening, high monochromatic IPCEs, and relative inertness to desorption into acidic media.

We examined two selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenoxanthylium analogue of the Texas-red core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp)-expressing Colo-26 cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, and for their co-localization with mitochondrial-specific agents in Colo-26 cells. Both compounds were extremely effective photosensitizers with values of EC50 ⩽ 4 × 10(-8)M toward Colo-26 cells with 1.0 J cm(-2) laser light delivered at 630 ± 2 nm., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

While H2O2 is a powerful oxidant, decomposing into environmentally benign H2O and O2, a catalyst is often required for reactions with H2O2 to proceed at synthetically useful rates. Organotellurium and organoselenium compounds catalyze the oxidation of halide salts to hypohalous acids using H2O2. When sequestered into xerogel monoliths, the xerogel-chalcogenide combinations have demonstrated increased catalytic activity relative to the organochalcogen compound alone in solution for the oxidation of halide salts to hypohalous acids with H2O2. Diorganotellurides, diorganoselenides, and diorganodiselenides bearing triethoxysilane functionalities were sequestered into xerogel monoliths and their catalytic activity and longevity were investigated. The longevity of the catalyst-xerogel combinations was examined by isolating and recycling the catalyst-xerogel combination. It was found tellurium-containing catalyst 3 and selenium-containing catalyst 8 maintained their catalytic activity through three recycling trials and adding electron-donating substituents to catalyst 3 also increased the catalytic rate. The presence of organotellurium and organoselenium groups in the +4 oxidation state was determined by X-ray photoelectron spectroscopy.

Hollow Gold Nanospheres (HGNs) exhibit a unique combination of properties which provide great scope for their use in many biomedical applications. However, they are highly unstable to changes in their surrounding environment and have a tendency to aggregate, particularly when exposed to high salt concentrations or changes in pH which is not ideal for applications such as cell imaging and drug delivery where stable solutions are required for efficient cellular uptake. Therefore there is a significant need to find a suitable stabilising agent for HGNs, however potential stabilising agents for these nanostructures have not previously been compared. Within this work we present an improved method for stabilising HGNs which simultaneously shifts the SPR from around 700 nm to 800 nm or greater. Herein, we compare three different materials which are commonly used as stabilising agents; polymers, sugars and silica in order to determine the optimum stabilising agent for HGNs. Analysis was performed using extinction spectroscopy and dynamic light scattering, supported with SEM imaging. Results showed PEG to be the most suitable stabilising agent for HGNs displaying both an increased stability to changes in salt concentration and pH as well as increased long term stability in solution. Furthermore, we demonstrate that in addition to increased stability, SERS detection can be achieved at both 1064 nm and 785 nm excitation. This combination of improved stability with a SPR in the NIR region along with SERS detection demonstrates the great potential for these nanostructures to be used in applications such as biological SERS imaging and drug delivery.

Surfaced enhanced Raman scattering (SERS) nanotags operating with 1280 nm excitation were constructed from reporter molecules selected from a library of 14 chalcogenopyrylium dyes containing phenyl, 2-thienyl, and 2-selenophenyl substituents and a surface of hollow gold nanoshells (HGNs). These 1280 SERS nanotags are unique as they have multiple chalcogen atoms available which allow them to adsorb strongly onto the gold surface of the HGN thus producing exceptional SERS signals at this long excitation wavelength. Picomolar limits of detection (LOD) were observed and individual reporters of the library were identified by principal component analysis and classified according to their unique structure and SERS spectra.

High sensitivity and specificity are two desirable features in biomedical imaging. Raman imaging has surfaced as a promising optical modality that offers both. Here we report the design and synthesis of a group of near-infrared absorbing 2-thienyl-substituted chalcogenopyrylium dyes tailored to have high affinity for gold. When adsorbed onto gold nanoparticles, these dyes produce biocompatible SERRS nanoprobes with attomolar limits of detection amenable to ultrasensitive in vivo multiplexed tumour and disease marker detection.

Over the past decade there has been significant development in hybrid polymer coatings exhibiting tunable surface morphology, surface charge, and chemical segregation-all believed to be key properties in antifouling (AF) coating performance. While a large body of research exists on these materials, there have yet to be studies on all the aforementioned properties in a colocalized manner with nanoscale spatial resolution. Here, we report colocalized atomic force microscopy, scanning Kelvin probe microscopy, and confocal Raman microscopy on a model AF xerogel film composed of 1:9:9 (mol:mol:mol) 3-aminopropyltriethoxysilane (APTES), n-octyltriethoxysilane (C8), and tetraethoxysilane (TEOS) formed on Al2O3. This AF film is found to consist of three regions that are chemically and physically unique in 2D and 3D across multiple length scales: (i) a 1.5 μm thick base layer derived from all three precursors; (ii) 2-4 μm diameter mesa-like features that are enriched in free amine (from APTES), depleted in the other species and that extend 150-400 nm above the base layer; and (iii) 1-2 μm diameter subsurface inclusions within the base layer that are enriched in hydrogen-bonded amine (from APTES) and depleted in the other species.

We examined a series of selenorhodamines with amide and thioamide functionality at the 5-position of a 9-(2-thienyl) substituent on the selenorhodamine core for their potential as photosensitizers for photodynamic therapy (PDT) in P-glycoprotein (P-gp) expressing cells. These compounds were examined for their photophysical properties (absorption, fluorescence, and ability to generate singlet oxygen), for their uptake into Colo-26 cells in the absence or presence of verapamil, for their dark and phototoxicity toward Colo-26 cells, for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their colocalization with mitochondrial specific agents in Colo-26 cells. Thioamide derivatives 16b and 18b were more effective photosensitizers than amide derivatives 15b and 17b. Selenorhodamine thioamides 16b and 18b were useful in a combination therapy to treat Colo-26 cells in vitro: a synergistic therapeutic effect was observed when Colo-26 cells were exposed to PDT and treatment with the cancer drug doxorubicin.

A series of chalcogenorhodamine dyes with oxygen, sulfur, and selenium atoms in the xanthylium core was synthesized and used as chromophores for solar hydrogen production with a platinized TiO2 catalyst. Solutions containing the selenorhodamine dye generate more hydrogen [181 turnover numbers (TONs) with respect to chromophore] than its sulfur (30 TONs) and oxygen (20 TONs) counterparts. This differs from previous work incorporating these dyes into dye-sensitized solar cells (DSSCs), where the oxygen- and selenium-containing species perform similarly. Ultrafast transient absorption spectroscopy revealed an ultrafast electron transfer under conditions for dye-sensitized solar cells and a slower electron transfer under conditions for hydrogen production, making the chromophore's triplet yield an important parameter. The selenium-containing species is the only dye for which triplet state population is significant, which explains its superior activity in hydrogen evolution. The discrepancy in rates of electron transfer appears to be caused by the presence or absence of aggregation in the system, altering the coupling between the dye and TiO2. This finding demonstrates the importance of understanding the differences between, as well as the effects of the conditions for DSSCs and solar hydrogen production.

Analogues of Texas red incorporating the heavy chalcogens S, Se, and Te atoms in the xanthylium core were prepared from the addition of aryl Grignard reagents to appropriate chalcogenoxanthone precursors. The xanthones were prepared via directed metalation of amide precursors, addition of dichalcogenide electrophiles, and electrophilic cyclization of the resulting chalcogenides with phosphorus oxychloride and triethylamine. The Texas red analogues incorporate two fused julolidine rings containing the rhodamine nitrogen atoms. Analogues containing two "half-julolidine" groups (a trimethyltetrahydroquinoline) and one julolidine and one "half-julolidine" were also prepared. The photophysics of the Texas red analogues were examined. The S-analogues were highly fluorescent, the Se-analogues generated single oxygen ( 1 O 2 ) efficiently upon irradiation, and the Te-analogues were easily oxidized to rhodamines with the telluroxide oxidation state. The tellurorhodamine telluroxides absorb at wavelengths ≥690 nm and emit with fluorescence maxima >720 nm. A mesityl-substituted tellurorhodamine derivative localized in the mitochondria of Colo-26 cells (a murine colon carcinoma cell line) and was oxidized in vitro to the fluorescent telluroxide.

The reaction of KSeO(t)Bu with 2-iodo-arylbenzamides gave benzamide ring-substituted, quinine-derived isoselenazolones 1b–1d. The reaction of PhSH with ortho-methyl-substituted isoselenazolone 1b gave selenol 3b, which is oxidized by H2O2 to regenerate 1b. Isoselenazolone 1b shows a high rate (0.33 × 103 μM min(−1)) of oxidation of PhSH with H2O2, which is ∼103-fold more active than ebselen (1a) and ≥30-fold more active than the other isoselenazolones of this study. Compound 1b shows less inhibition of the growth of yeast cells than 1a.

Biofouling on ships and boats, characterized by aquatic bacteria and small organisms attaching to the hull, is an important global issue, since over 80000 tons of antifouling paint is used annually. This biofilm, which can form in as little as 48 hours depending on water temperature, increases drag on watercraft, which greatly reduces their fuel efficiency. In addition, biofouling can lead to microbially induced corrosion (MIC) due to H2S formed by the bacteria, especially sulfate-reducing bacteria. When the International Maritime Organization (IMO) international convention banned the use of effective but environmentally damaging coatings containing tributyl tin in 2008, the development of clean and effective antifouling systems became more important than ever. New nonbiocidal coatings are now in high demand. Scientists have developed new polymers, materials, and biocides, including new elastomeric coatings that they have obtained by improving the original silicone (polydimethylsiloxane) formulation patented in 1975. However, the high cost of silicones, especially of fluoropolymer-modified silicones, has generally prevented their large-scale diffusion. In 2009, traditional antifouling coatings using cuprous oxide formulated in copolymer paints still represented 95% of the global market volume of anti-fouling paints. The sol-gel nanochemistry approach to functional materials has emerged as an attractive candidate for creating low fouling surfaces due to the unique structure and properties of silica-based coatings and of hybrid inorganic-organic silicas in particular. Sol-gel formulations easily bind to all types of surfaces, such as steel, fiberglass, aluminum, and wood. In addition, they can cure at room temperature and form thin glassy coatings that are markedly different from thick silicone elastomeric foul-releasing coatings. Good to excellent performance against biofouling, low cure temperatures, enhanced and prolonged chemical and physical stability, ease of application, and the waterborne nature of sol-gel coatings all support the diffusion of these paints to efficiently reduce the accumulation of fouling layers on valued surfaces immersed in marine or fluvial waters. Furthermore, sol-gel glassy coatings are transparent and can be effectively applied to optical devices, windows, and solar panels used in lake, fluvial, or marine environments. Sol-gel technology is eminently versatile, and the first generation sol-gel paints have already shown good performance. Even so, vast opportunities still exist for chemists to develop novel sol-gel derived coatings to both prevent biofouling and enhance the hydrodynamic properties of boat and ship hulls. Moreover, researchers have prepared and applied multifunctional sol-gel coatings providing protection against both biofouling and corrosion. They have tested these in the marine environment with good preliminary results. In this Account, we discuss some of our new strategies for the controlled functionalization of surfaces for the development of efficient antifouling and foul-releasing systems and summarize the main achievements with biocidal and nonbiocidal sol-gel coatings. We conclude by giving insight into the marine coatings and sol-gel products markets, providing arguments to justify our conclusion that the sol-gel coatings technology is now a mature platform for the development of economically viable and environmentally friendly antifouling and foul-release formulations of enhanced performance.

Chalcogenopyrylium monomethine dyes were prepared via condensation of a 4-methylchalcogenopyrylium compound with a chalcogenopyran-4-one bearing a 4-(diethoxyphosphoryl)phenyl substituent (or the phosphonic acid derivative). The dyes have absorbance maxima of 603-697 nm in the window where the solar spectrum is most intense. The dyes formed H-aggregates on TiO2, increasing the light-harvesting efficiency of the dyes. Shortcircuit photocurrent action spectra were acquired to evaluate the influence of dye structure on the photoelectrochemical performance.

Multidrug resistance proteins (MRPs) mediate the ATP-dependent efflux of structurally diverse compounds, including anticancer drugs and physiologic organic anions. Five classes of chalcogenopyrylium dyes (CGPs) were examined for their ability to modulate transport of [(3)H]estradiol glucuronide (E(2)17βG; a prototypical MRP substrate) into MRP-enriched inside-out membrane vesicles. Additionally, some CGPs were tested in intact transfected cells using a calcein efflux assay. Sixteen of 34 CGPs inhibited MRP1-mediated E(2)17βG uptake by >50% (IC50 values: 0.7-7.6 µM). Of 9 CGPs with IC50 values ≤2 µM, two belonged to class I, two to class III, and five to class V. When tested in the intact cells, only 4 of 16 CGPs (at 10 µM) inhibited MRP1-mediated calcein efflux by >50% (III-1, V-3, V-4, V-6), whereas a fifth (I-5) inhibited efflux by just 23%. These five CGPs also inhibited [(3)H]E(2)17βG uptake by MRP4. In contrast, their effects on MRP2 varied, with two (V-4, V-6) inhibiting E(2)17βG transport (IC(50) values: 2.0 and 9.2 µM) and two (V-3, III-1) stimulating transport (>2-fold), whereas CGP I-5 had no effect. Strikingly, although V-3 and V-4 had opposite effects on MRP2 activity, they are structurally identical except for their chalcogen atom (Se versus Te). This study is the first to identify class V CGPs, with their distinctive methine or trimethine linkage between two disubstituted pyrylium moieties, as a particularly potent class of MRP modulators, and to show that, within this core structure, differences in the electronegativity associated with a chalcogen atom can be the sole determinant of whether a compound will stimulate or inhibit MRP2.

The effect of a series of xerogel coatings modified with aminoalkyl/fluorocarbon/hydrocarbon groups on the adhesion of a new test species, the filamentous brown alga Ectocarpus crouaniorum, has been explored, and compared with the green alga Ulva linza. The results showed that E. crouaniorum adhered weakly to the less polar, low wettability coatings in the series, but stronger adhesion was shown on polar, higher surface energy coatings containing aminoalkyl groups. The results from a separate series of coatings tuned to have similar surface energies and polarities after immersion in artificial seawater (ASW), but widely different surface charges, demonstrated that surface charge was more important than surface energy and polarity in determining the adhesion strength of both E. crouaniorum and U. linza on xerogel coatings. No correlation was found between adhesion and contact angle hysteresis. X-ray photoelectron spectroscopy analysis of samples after immersion in ASW confirmed the presence of charged ammonium groups on the surface of the aminoalkylated coatings.

Isoselenazolones were synthesized by a copper-catalyzed Se-N bond forming reaction between 2-halobenzamides and selenium powder. The catalytic activity of the various isoselenazolones was studied in the bromolactonization of pent-4-enoic acid. Isoselenazolone 9 was studied as a catalyst in several reactions: the bromolactonization of a series of alkenoic acids with bromine or N-bromosuccinimide (NBS) in the presence of potassium carbonate as base, the bromoesterification of a series of alkenes using NBS and a variety of carboxylic acids, and the oxidation of secondary alcohols to ketones using bromine as an oxidizing reagent. Mechanistic details of the isoselenazolone-catalyzed bromination reaction were revealed by (77)Se NMR spectroscopic and ES-MS studies. The oxidative addition of bromine to the isoselenazolone gives the isoselenazolone(IV) dibromide, which could be responsible for the activation of bromine under the reaction conditions. Steric effects from an N-phenylethyl group on the amide of the isoselenazolone and electron-withdrawing fluoro substituents on the benzo fused-ring of the isoselenazolone appear to enhance the stability of the isoselenazolone as a catalyst for the bromination reaction.

The P-glycoprotein (P-gp, ABCB1) drug pump protects us from toxic compounds and confers multidrug resistance. Each of the homologous halves of P-gp is composed of a transmembrane domain (TMD) with 6 TM segments followed by a nucleotide-binding domain (NBD). The predicted drug- and ATP-binding sites reside at the interface between the TMDs and NBDs, respectively. Crystal structures and EM projection images suggest that the two halves of P-gp are separated by a central cavity that closes upon binding of nucleotide. Binding of drug substrates may induce further structural rearrangements because they stimulate ATPase activity. Here, we used disulfide cross-linking with short (8 Å) or long (22 Å) cross-linkers to identify domain-domain interactions that activate ATPase activity. It was found that cross-linking of cysteines that lie close to the LSGGQ (P517C) and Walker A (I1050C) sites of NBD1 and NBD2, respectively, as well as the cytoplasmic extensions of TM segments 3 (D177C or L175C) and 9 (N820C) with a short cross-linker activated ATPase activity over 10-fold. A pyrylium compound that inhibits ATPase activity blocked cross-linking at these sites. Cross-linking between the NBDs was not inhibited by tariquidar, a drug transport inhibitor that stimulates P-gp ATPase activity but is not transported. Cross-linking between extracellular cysteines (T333C/L975C) predicted to lock P-gp into a conformation that prevents close NBD association inhibited ATPase activity. The results suggest that trapping P-gp in a conformation in which the NBDs are closely associated likely mimics the structural rearrangements caused by binding of drug substrates that stimulate ATPase activity.

Twelve thiorhodamine derivatives have been examined for their ability to stimulate the ATPase activity of purified human P-glycoprotein (P-gp)-His(10), to promote uptake of calcein AM and vinblastine into multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells, and for their rates of transport in monolayers of multidrug-resistant, P-gp-overexpressing MDCKII-MDR1 cells. The thiorhodamine derivatives have structural diversity from amide and thioamide functionality (N,N-diethyl and N-piperidyl) at the 5-position of a 2-thienyl substituent on the thiorhodamine core and from diversity at the 3-amino substituent with N,N-dimethylamino, fused azadecalin (julolidyl), and fused N-methylcyclohexylamine (half-julolidyl) substituents. The julolidyl and half-julolidyl derivatives were more effective inhibitors of P-gp than the dimethylamino analogues. Amide-containing derivatives were transported much more rapidly than thioamide-containing derivatives., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Twenty-seven chalcogenopyrylium derivatives varying in the heteroatom of the pyrylium core and substituents at the 2-, 4-, and 6-positions were examined for their effect on human MRP1-mediated uptake of tritiated estradiol glucuronide into inside-out membrane vesicles, their affinity for and ability to stimulate the ATPase activity of purified human P-glycoprotein (P-gp)-His(10), and their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant cells. Differences in their effects on MRP1 and P-gp activity were noted, and a second set of thiopyrylium compounds with systematic substituent changes was examined to refine these differences further. Derivatives with tert-butyl substituents in the 2- and 6-positions had the lowest inhibitory activity toward both transporters. Derivatives with thioamide functionality in the 4-position were more active against MRP1 than derivatives with amide functionality. Conversely, derivatives with amide functionality in the 4-position were more active in P-gp than derivatives with thioamide functionality.

Chalcogenorhodamine dyes bearing phosphonic acids and carboxylic acids were compared as sensitizers of nanocrystalline TiO(2) in dye-sensitized solar cells (DSSCs). The dyes were constructed around a 3,6-bis(dimethylamino)chalcogenoxanthylium core and varied in the 9 substituent: 5-carboxythien-2-yl in dyes 1-E (E = O, Se), 4-carboxyphenyl in dyes 2-E (E = O, S), 5-phosphonothien-2-yl in dyes 3-E (E = O, Se), and 4-phosphonophenyl in dyes 4-E (E = O, Se). All dyes adsorbed to TiO(2) as mixtures of H aggregates and monomers, which exhibited broadened absorption spectra relative to those of purely amorphous monolayers. Surface coverages of dyes and the extent of H aggregation varied minimally with the surface-attachment functionality, the structure of the 9-aryl group, and the identity of the chalcogen heteroatom. Carboxylic acid-functionalized dyes 1-E and 2-E desorbed rapidly and completely from TiO(2) into acidified CH(3)CN, but phosphonic acid-functionalized dyes 3-E and 4-E persisted on TiO(2) for days. Short-circuit photocurrent action spectra of DSSCs corresponded closely to the absorptance spectra of dye-functionalized films; thus, H aggregation did not decrease the electron-injection yield or charge-collection efficiency. Maximum monochromatic incident photon-to-current efficiencies (IPCEs) of DSSCs ranged from 53 to 95% and were slightly higher for carboxylic acid-functionalized dyes 1-E and 2-E. Power-conversion efficiencies of DSSCs under white-light illumination were low (<1%), suggesting that dye regeneration was inefficient at high light intensities. The photoelectrochemical performance (under monochromatic or white-light illumination) of 1-E and 2-E decayed significantly within 20-80 min of the assembly of DSSCs, primarily because of the desorption of the dyes. In contrast, the performance of phosphonic acid-functionalized dyes remained stable or improved slightly on similar timescales. Thus, replacing carboxylic acids with phosphonic acids increased the inertness of chalcogenorhodamine-TiO(2) interfaces without greatly impacting the aggregation of dyes or the interfacial electron-transfer reactivity.

Oxygen responsive sensor platforms were fabricated by pin printing tris(4,7-diphenyl-1,10-phenanthroline)ruthenium(II) ([Ru(dpp)(3)](2+)) doped sols onto wavelength tuned reflective Bragg gratings. In an epi-luminescence configuration, these Bragg gratings (Gr) were designed to selectively reflect the O(2) responsive [Ru(dpp)(3)](2+) emission toward the detector to enhance the detected signal magnitude. The xerogel based sensors were formed onto (i) glass (XGl), (ii) directly on top of the grating (XGrGl), or (iii) on the glass substrate opposite the grating (XGlGr). The results show that all sensors exhibit linear, statistically equivalent O(2) sensitivities, and the XGrGl platform yields up to an 8-fold increase in relative detected analytical signal (RDAS) in comparison to the control (XGl) platform., (© 2011 American Chemical Society)

The reaction mechanism of the GPx-like oxidation of PhSH with H(2)O(2) catalyzed by selenoxides proceeds via formation of the hydroxy perhydroxy selenane, which is a stronger oxidizing agent than selenoxide. A hydroxy perhydroxy selenane intermediate was observed by electrospray ionization mass spectrometry and (77)Se NMR spectroscopy in reactions of selenoxide 8 with H(2)O(2).The initial velocity of oxidation of PhSH by H(2)O(2) with selenoxide 8 is 4 orders of magnitude higher than that of 8 without peroxide. Selenoxide 8 is not reduced to selenide 6 by PhSH in the presence of H(2)O(2). While electronic substituent effects have minimal impact on the catalytic performance of selenoxides, chelating groups increase the rate of catalysis., (© 2011 American Chemical Society)

This article is a highlight of the paper by Anquez et al. in this issue of Photochemistry and Photobiology and describes the potential benefits of direct excitation of molecular oxygen to produce singlet oxygen ((1)O(2)) rather than using a photosensitizer. Due to its simplicity, the direct excitation of molecular oxygen can potentially overcome problems associated with systemic administration of dyes, such as skin photosensitivity and the clearance of free sensitizer from the body. However, concerns associated with the technique include indiscriminate generation of extracellular and intracellular (1)O(2), the difficulty of controlling necrotic vs apoptotic cell death and the possible consequences of thermal effects., (© 2011 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2011 The American Society of Photobiology.)

Four-component xerogel films consisting of 1 mole-% n-octadecyltrimethoxysilane (C18) and 50 mole-% tetraethoxysilane (TEOS) in combination with 1-24 mole-% tridecafluoro-1,1,2,2-tetrahydrooctyltriethoxysilane (TDF) and 25-48 mole-% n-octyltriethoxysilane (C8) and a 1:49:50 mole-% C18/TDF/TEOS were prepared. Settlement of barnacle cyprids and removal of juvenile barnacles, settlement of zoospores of the alga Ulva linza, and strength of attachment of 7-day sporelings (young plants) of Ulva were compared amongst the xerogel formulations. Several of the xerogel formulations were comparable to poly(dimethylsiloxane) elastomer with respect to removal of juvenile barnacles and removal of sporeling biomass. The 1:4:45:50 and 1:14:35:50 C18/TDF/C8/TEOS xerogels displayed some phase segregation by atomic force microscopy (AFM) pre- and post-immersion in water. Imaging reflectance infrared microscopy showed the formation of islands of alkane-rich and perfluoroalkane-rich regions in these same xerogels both pre- and post-immersion in water. Surface energies were unchanged upon immersion in water for 48 h amongst the TDF-containing xerogel coatings. AFM measurements demonstrated that surface roughness on the 1:4:45:50 and 1:14:35:50 C18/TDF/C8/TEOS xerogel coatings decreased upon immersion in water.

Five non-biocidal xerogel coatings were compared to two commercial non-biocidal coatings and a silicone standard with respect to antifouling (AF)/fouling-release (FR) characteristics. The formation and release of biofilm of the marine bacterium Cellulophaga lytica, the attachment and release of the microalga Navicula incerta, and the fraction removal and critical removal stress of reattached adult barnacles of Amphibalanus amphitrite were evaluated in laboratory assays. Correlations of AF/FR performance with surface characteristics such as wettability, surface energy, elastic modulus, and surface roughness were examined. Several of the xerogel coating compositions performed well against both microfouling organisms while the commercial coatings performed less well toward the removal of microalgae. Reattached barnacle adhesion as measured by critical removal stress was significantly lower on the commercial coatings when compared to the xerogel coatings. However, two xerogel compositions showed release of 89-100% of reattached barnacles. These two formulations were also tested in the field and showed similar results.

Mixtures of n-octadecyltrimethoxysilane (C18, 1-5 mole-%), n-octyltriethoxysilane (C8) and tetraethoxysilane (TEOS) gave xerogel surfaces of varying topography. The 1:49:50 C18/C8/TEOS xerogel formed 100-400-nm-wide, 2-7-nm deep pores by AFM while coatings with ≥3% C18 were free of such features. Segregation of the coating into alkane-rich and alkane-deficient regions in the 1:49:50 C18/C8/TEOS xerogel was observed by IR microscopy. Immersion in ASW for 48 h gave no statistical difference in surface energy for the 1:49:50 C18/C8/TEOS xerogel and a significant increase for the 50:50 C8/TEOS xerogel. Settlement of barnacle cyprids and removal of juvenile barnacles, settlement of zoospores of the alga Ulva linza, and strength of attachment of 7-day sporelings were compared amongst the xerogel formulations. Settlement of barnacle cyprids was significantly lower in comparison to glass and polystyrene standards. The 1:49:50 and 3:47:50 C18/C8/TEOS xerogels were comparable to PDMSE with respect to removal of juvenile barnacles and sporeling biomass, respectively.

Rhodamine photosensitizers (PSs) substituting S or Se for O in the xanthene ring give turnover numbers (TONs) as high as 9000 for the generation of hydrogen via the reduction of water using [Co(III)(dmgH)(2)(py)Cl] (where dmgH = dimethylglyoximate and py = pyridine) as the catalyst and triethanolamine as the sacrificial electron donor. The turnover frequencies were 0, 1700, and 5500 mol H(2)/mol PS/h for O, S, and Se derivatives, respectively (Φ(H(2)) = 0%, 12.2%, and 32.8%, respectively), which correlates well with relative triplet yields estimated from quantum yields for singlet oxygen generation. Phosphorescence from the excited PS was quenched by the sacrificial electron donor. Fluorescence lifetimes were similar for the O- and S-containing rhodamines (∼2.6 ns) and shorter for the Se analog (∼0.1 ns). These data suggest a reaction pathway involving reductive quenching of the triplet excited state of the PS giving the reduced PS(-) that then transfers an electron to the Co catalyst. The longer-lived triplet state is necessary for effective bimolecular electron transfer. While the cobalt/rhodamine/triethanolamine system gives unprecedented yields of hydrogen for the photoreduction of water, mechanistic insights regarding the overall reaction pathway as well as system degradation offer significant guidance to developing even more stable and efficient photocatalytic systems.

Previous work has shown that organosilica-based xerogels have the potential to control biofouling. In this study, modifications of chemistry were investigated with respect to their resistance to marine slimes and to settlement of barnacle cyprids. Adhesion force measurements of bovine serum albumin (BSA)-coated atomic force microscopy (AFM) tips to xerogel surfaces prepared from aminopropylsilyl-, fluorocarbonsilyl-, and hydrocarbonsilyl-containing precursors, indicated that adhesion was significantly less on the xerogel surfaces in comparison to a poly(dimethylsiloxane) elastomer (PDMSE) standard. The strength of adhesion of BSA on the xerogels was highest on surfaces with the highest and the lowest critical surface tensions, gamma(C) and surface energies, gamma(S), and duplicated the 'Baier curve'. The attachment to and removal of cells of the diatom Navicula perminuta from a similar series of xerogel surfaces were examined. Initial attachment of cells was comparable on all of the xerogel surfaces, but the percentage removal of attached cells by hydrodynamic shear stress increased with gamma(C) and increased wettability as measured by the static water contact angle, theta(Ws), of the xerogel surfaces. The percentage removal of cells of Navicula was linearly correlated with both properties (R(2) = 0.74 for percentage removal as a function of theta(Ws) and R(2) = 0.69 for percentage removal as a function of gamma(C)). Several of the aminopropylsilyl-containing xerogels showed significantly greater removal of Navicula compared to a PDMSE standard. Cypris larvae of the barnacle B. amphitrite showed preferred settlement on hydrophilic/higher energy surfaces. Settlement was linearly correlated with theta(Ws) (R(2) = 0.84) and gamma(C) (R(2) = 0.84). Hydrophilic xerogels should prove useful as coatings for boats in regions where fouling is dominated by microfouling (protein and diatom slimes).