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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.

Multiplexed imaging of 8 molecular targets with SERS nanoprobes in mice reveals spatially heterogeneous tumor responses to immunotherapy. Multichannel image segmentation enables classification of the tumor regions into responders and naïve.

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.

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

Aerobic oxidation of 2-aryl-1,2,3,4-tetrahydroisoquinolines was achieved photocatalytically using chalcogenorosamine photocatalysts and LED irradiation. The photocatalytic aza-Henry reaction betwee...

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.

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.

Molecules with a strong two-photon response have gained significant interest because of their applications in two-photon imaging, all-optical switching, and energy up-conversion. The surface-enhanced hyper-Raman scattering (SEHRS) of tetramethyl chalcogenorosamines are taken on- and off-resonance and compared to time-dependent density functional theory calculations. Specifically, changes in the SEHRS spectra are tracked as a function of structural geometry because of perturbations induced by larger chalcogen atom substitutions to the xanthene ring. Here we show that the spectral changes and non-Condon effects can be understood by tracking the vibrational normal modes and the vibrationally induced changes to the highest occupied molecular orbitals. With a system in place to explore the relationship between structural geometry and nonlinear properties, various rhodamine derivatives can be characterized as a means to optimally design a series of two-photon bright compounds.

Various modern solar light-harvesting systems, including those used in photovoltaics and solar fuel production, depend on efficient electron transfer from a surface-bound molecular dye to nanoscopic semiconductor particles. However, the productive electron transfer competes with a variety of other relaxation pathways for the dye, and the dominant pathway can change dramatically depending on its environment. A new sulfur-substituted thiorhodamine dye was synthesized having exceptional light-harvesting qualities for solar energy applications and for solar hydrogen production in particular. The dye was created with a thiophene spacer bearing a phosphonate-ester (1-Ester) or phosphonic-acid (1-Acid) allowing for excellent solubility in MeCN or the ability to functionalize metal oxide semiconductor nanoparticles such as TiO2. While 1-Ester is found to be fully monomeric in MeCN, 1-Acid readily forms H-aggregated dimers which, upon photoexcitation, undergo charge separation to an ion pair (IP) in 1.5 ps. For 1-...

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 multicellular tumour spheroids (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.

Aerobic oxidation of thiols to disulfides was achieved photocatalytically using a tellurorhodamine chromophore (9-mesityl-3,6-bis(dimethylamino)telluroxanthylium hexafluorophosphate) as both the sensitizer and catalyst. The proposed mechanism, supported experimentally and computationally with DFT, involves the formation of a tellurorhodamine telluroxide from reaction with water and singlet oxygen generated by irradiation of the tellurorhodamine. The oxidation to the telluroxide is accompanied by the formation of hydrogen peroxide. The telluroxide oxidizes thiols to regenerate the tellurorhodamine and the disulfide plus water. Mechanistically, DFT suggests adding two thiols to the telluroxide with the loss of H2O to give a trigonal-bipyramidal Te(IV), which undergoes concerted loss of disulfide to regenerate 1. Oxidation of thiophenol and 2-naphthalenethiol was complete after 2 h of irradiation with visible light under atmospheric conditions. Oxidation of the electron-poor 2,6-dichlorothiophenol, the steri...

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 Forster resonance energy transfer.

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).

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.

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.

Extended rhodamines were prepared by inserting an additional fused benzene ring into the rhodamine xanthylium core. The synthesis of “bent” dyes 4-E (E = S, Se, Te) began with regioselective lithiation of the 1-position of N,N-diisopropyl 6-dimethylamino-2-naphthamide (11b) with n-BuLi/TMEDA (≥25:1 1- vs 3-lithiation) followed by addition of a dichalcogenide electrophile. The synthesis of “linear” dyes 5-E (E = S, Se, Te) began with regioselective lithiation of the 3-position of N,N-diethyl 6-dimethylamino-2-naphthamide (11a) with lithium tetramethylpiperidide (≥50:1 3- vs 1-lithiation) followed by addition of a dichalcogenide electrophile. Dyes 4-E and 5-E have absorption maxima in the 633–700 nm range. Dyes 4-E generate singlet oxygen upon irradiation while dyes 4-S and 5-S are highly fluorescent, with quantum yields for fluorescence of 0.47 and 0.18, respectively. DFT calculations were performed on the 4-E and 5-E chromophores. For the dyes 4-E, the lowest energy excitation is due solely to the HOMO–LU...

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 label 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.

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.

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.

We show the large environmental and practical impact of nanochemistry innovation by telling the story of how the sol-gel hybrid coating technology was subtly adapted to meet the urgent demand for clean antifouling marine coatings for vessels of widely different size, composition, and operation requirements.

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.

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.

Diaryl ditellurides were oxidized in situ to give aryltellurinic acids, which catalyzed the oxidation of NaBr with H2O2 in buffered aqueous solutions. The aryltellurinic acids were slowly oxidized under the reaction conditions to the corresponding telluronic acids, which did not catalyze oxidation of NaBr with H2O2. Both 4-(methoxyphenyl)tellurinic acid and 4-(methoxyphenyl)telluronic acid were characterized in solution by 125Te NMR and for their effectiveness as catalysts in kinetics studies. The effectiveness of the tellurinic acids as catalysts was very sensitive to electron demand in the intermediates present during the course of the reaction. Electron-withdrawing substituents favor the deprotonated tellurinic acid (tellurinate) in solution, while electron-donating substituents favor the protonated tellurinic acid. Of the nine ditellurides screened for their ability to accelerate the oxidation of NaBr with H2O2, diphenyl ditelluride emerged as the most active. The addition of only 0.20 mol % of this d...

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 (1O2) 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.

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 S1via rotation of the aryl group and the excited state population rapidly equilibrates between S1 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.

Several 9-aryl-3,6-diaminotelluroxanthylium dyes with phenyl, 2-methylphenyl, and 2,4,6-trimethylphenyl substituents at the 9-position were prepared. The characterization of these compounds included determination of 125Te NMR spectra, fluorescence quantum yields (ΦF), and quantum yields for the generation of singlet oxygen [Φ(1O2)]. While these compounds were essentially nonfluorescent (ΦF < 0.005), they produce 1O2 with Φ(1O2) between 0.43 and 0.90. The tellurorosamines were oxidized with 1O2 via self-photosensitization to the corresponding telluroxides, which allowed their preparation free of excess oxidant. Telluroxides with a 9-(2-methylphenyl) or 9-(2,4,6-trimethylphenyl) substituent were fluorescent with quantum yields for fluorescence between 0.20 and 0.31. Steric bulk at the 9-position of the resulting telluroxides impacted rates of inter- and intramolecular attack of nucleophiles and stability of the telluroxide in aqueous media near physiological pH. The yield of reduction of the telluroxide wit...

We used transient absorption spectroscopy to characterize excited-state electron injection from a 2,7-bis(dimethylamino)-9-(5-phosphonothien-2-yl)selenoxanthylium dye (3-Se) into TiO2. Dye 3-Se adsorbed to TiO2 via the phosphonic acid group as a mixture of H-aggregates and monomers. Injection of electrons from photoexcited 3-Se into TiO2 yielded the dication radical (3-Se+) and an associated transient absorption at wavelengths shorter than 540 nm, the amplitude of which was proportional to the quantum yield of electron injection (ϕinj). Our data revealed that ϕinj from H-aggregated 3-Se was (2.0 ± 1.3)-fold greater than from monomeric 3-Se; therefore, H-aggregation increased the efficiencies of both light-harvesting and electron injection. Comparison with our reported data for the analogous carboxylic acid-functionalized dye (1-Se) revealed that ϕinj via the carboxylate linkage was (2.3 ± 1.1)-fold greater than via the phosphonate linkage. Thus, electron-injection reactivity is sensitive to both the aggregation state and the surface-anchoring mode of these chalcogenorhodamine dyes. The decrease of ϕinj for 3-Se is offset by its enhanced stability and persistence on TiO2, rendering the phosphonic acid-functionalized and H-aggregated dye a particularly attractive sensitizer.

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 by50% (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 by50% (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 design and synthesis of imidazolium-containing diselenides 4a–c is described. The introduction of the N-methylimidazolium group gives freely soluble compounds in water, unlike the majority of common organic diselenides. Catalytic amounts of 4a–c effectively promote bromination of organic substrates using a safe and inexpensive NaBr/H2O2 system in water. Kinetics experiments revealed that the bromination of 4-pentenoic acid has a first-order dependence with respect to both NaBr and H2O2 concentrations The rate of reaction was also sensitive to the pH of the solution. Preparative reactions showed that, compared to 4a, diphenyl diselenide 5 was a poor catalyst and the ionic liquid 1-benzyl-3-methylimidazolium bromide 6 showed no catalytic activity with H2O2 indicating synergy from the combined functionality.

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.

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.

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.

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).

21,23-Ditelluraporphyrins 3, 9, and 16−18 bearing phenyl, 4-methoxyphenyl, and/or 3,4,5-trimethoxyphenyl meso substituents were prepared by the condensation of 2,5-di[hydroxy(aryl)methyl]tellurophenes 12 with 2,5-di[2-pyrrolo(aryl)methyl]tellurophenes 15 in the presence of BF3−etherate followed by oxidation with p-chloranil. Compounds 15 were prepared from tellurophenes 12 with pyrrole and BF3−etherate. Tellurophenes 12 were prepared in 44−72% isolated yield by the addition of 1,6-diarylhexa-2,4-diyn-1,6-diols 13 to the reduction product of Te powder and LiBHEt3. No additional Lewis acid was necessary in these reactions. Coupling of 1-aryl-2-propyn-1-ols (14) with CuCl, pyridine, and air in MeOH gave diyndiols 13. 26,28-Ditellurasapphyrin 10 was isolated in 0.6% yield from the reaction mixture that produced 9 in 12% isolated yield. The X-ray structure of 10 showed a nearly planar sapphyrin core with the Te atoms of both tellurophene rings pointing to the center of the core. 30,33-Ditellurarubyrin 11 was i...

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.

Novel rhodamine dyes were prepared from xanthone precursors in a 'one-pot' procedure via reaction of the xanthone with trifluoromethanesulfonic anhydride followed by Pd-mediated Suzuki coupling between the xanthone triflate and an arylboroxin. Rhodamines with 9-(3- or 4-carboxyphenyl) and 9-(3-nitrophenyl) substituents were prepared by this procedure. The procedure also works well with thio- and selenoxanthones, but not with telluroxanthones.

Xerogel films with uniform surface topogrophy, as determined by scanning electron microscopy, atomic force microscopy (AFM), and time-of-flight secondary ion mass spectrometry, were prepared from aminopropylsilyl-, fluorocarbonsilyl-, and hydrocarbonsilyl- containing precursors. Young's modulus was determined from AFM indentation measurements. The xerogel coatings gave reduced settlement of zoospores of the marine fouling alga Ulva compared to a poly(dimethylsiloxane) elastomer (PDMSE) standard. Increased settlement correlated with decreased water wettability as measured by the static water contact angle, theta(Ws), or with decreased polar contribution (gamma(P)) to the surface free energy (gamma(S)) as measured by comprehensive contact angle analysis. The strength of attachment of 7-day sporelings (young plants) of Ulva on several of the xerogels was similar to that on PDMSE although no overall correlation was observed with either theta(Ws) or gamma(S). For sporelings attached to the fluorocarbon/hydrocarbon-modified xerogels, the strength of attachment increased with increased water wettability. The aminopropyl-modified xerogels did not follow this trend.

Various 1-[[bis(1-methylethyl)amino]carbonyl]-2-(dibromo-n-alkylseleno)ferrocene derivatives reacted with 2 equiv of 4-pentenoic acid or 5-hexenoic acid to give the corresponding γ- or δ-lactones, respectively, from transfer of the alkyl group bound to selenium to the terminal alkene carbon. In the lactone cyclization, 1-[[bis(1-methylethyl)amino]carbonyl]-2-(bromoselenenyl)ferrocene (25) is formed and reacts with a second equivalent of the alkenoic acid to give either 5-[1-[[bis(1-methylethyl)amino]carbonyl]ferrocene-2-selenenylmethyl]tetrahydro-2-furanone (23) or 6-[1-[[bis(1-methylethyl)amino]carbonyl]ferrocene-2-selenenylmethyl]tetrahydro-2H-pyran-2-one (26) as a mixture of diastereomers in yields comparable to the corresponding γ- or δ-lactone. The addition of 1-[[bis(1-methylethyl)amino]carbonyl]-2-(dibromo-n-butylseleno)ferrocene to 3-butenoic acid gave alkyl transfer to the internal alkene carbon and formation of the γ-lactone. Density functional theory (DFT) geometry optimizations were performed ...

We have examined 46 tetramethylrosamine/rhodamine derivatives with structural diversity in the heteroatom of the xanthylium core, the amino substituents of the 3- and 6-positions, and the alkyl, aryl, or heteroaryl group at the 9-substituent. These compounds were examined for affinity and ATPase stimulation in isolated MDR3 CL P-gp and human P-gp-His(10), for their ability to promote uptake of calcein AM and vinblastine in multidrug-resistant MDCKII-MDR1 cells, and for transport in monolayers of MDCKII-MDR1 cells. Thioamide 31-S gave K(M) of 0.087 microM in human P-gp. Small changes in structure among this set of compounds affected affinity as well as transport rate (or flux) even though all derivatives examined were substrates for P-gp. With isolated protein, tertiary amide groups dictate high affinity and high stimulation while tertiary thioamide groups give high affinity and inhibition of ATPase activity. In MDCKII-MDR1 cells, the tertiary thioamide-containing derivatives promote uptake of calcein AM and have very slow passive, absorptive, and secretory rates of transport relative to transport rates for tertiary amide-containing derivatives. Thioamide 31-S promoted uptake of calcein AM and inhibited efflux of vinblastine with IC(50)'s of approximately 2 microM in MDCKII-MDR1 cells.

4-(Hydroxymethyl)phenyl benzyl selenoxide (4) sequestered in a halide-permeable, Class II xerogel formed from 10/90 (mol/mol) 3-aminopropyltriethoxysilane/tetraethoxysilane catalyzes the bromination of organic substrates (4-pentenoic acid, 3,5-dihydroxybenzoic acid, 1,3,5-trimethoxybenzene, N-phenylmorpholine, and N,N-dimethylaniline) with NaBr and H2O2. Catalyst performance (reaction rate) when sequestered within the halide-permeable xerogel is 23-fold greater in comparison to xerogel-free catalyst in solution. The catalyst is easily separated from the reaction mixture via filtration and the recovered catalyst can be reused without loss of activity through formation of the first 80 mol of product per mole of catalyst.

Chalcogenoxanthylium dyes were characterized as sensitizers of nanocrystalline titania in dye-sensitized solar cells (DSSCs). Four series of dyes were characterized: 2,7-bis(dimethylamino)-9-(2-thienyl-5-carboxy)chalcogenoxanthylium dyes (1-E, where E = O, S, Se); 2,7-bis(dimethylamino)-9-(3-thienyl-2-carboxy)chalcogenoxanthylium dyes (2-E, where E = S, Se); a 2,7-bis(dimethylamino)-9-(2-thienyl)selenoxanthylium dye (3-Se); 4-Se, a constrained analog of 1-Se. The orientation and aggregation state of the dyes were controlled by varying the position of the surface-attachment group relative to the xanthylium core. Series 1 dyes and 4-Se underwent H-aggregation on titania surfaces, whereas series 2 dyes adsorbed in amorphous monolayers. (3-Se did not adsorb appreciably to titania films, due to the lack of a tethering group.) The H-aggregated dyes exhibited broader absorption bands, increased light-harvesting efficiencies, and improved photoelectrochemical performance compared to the dyes which adsorbed in amo...

Thiaporphyrins 2–8 were prepared as analogues of 5,20-diphenyl-10,15-bis[4-(carboxymethyleneoxy)-phenyl]-21,23- dithiaporphyrin (1) to examine the effect of structural modifications: substituent changes in meso aryl groups of dithiaporphyrins with one water-solubilizing group (2–5), dihydroxylation of a pyrrole double bond and reduction to dihydroxychlorins (6 and 7), and the removal of two meso aryl groups to give unsubstituted meso positions (8). The impact of these structural modifications was measured in both physicochemical (UV spectra, generation of singlet oxygen, lipophilicity, and aggregate formation) and biological properties (dark toxicity and phototoxicity, cellular uptake, and subcellular localization). Mono-functionalized porphyrins had much higher lipophilicity than di-functionalized porphyrin 1 and, consequently, formed more aggregates in aqueous media. The formation of aggregates might lower the efficiency of lipophilic porphyrins as photosensitizers. Interestingly, dihydroxylation of a core pyrrole group in the dithiaporphyrin core did not affect either the absorption spectrum or the efficiency for generating singlet oxygen. The phototoxicity of dihydroxydithiachlorins mainly depended on their intracellular uptake. The potent phototoxicity of 6, IC50 = 0.18 μM, was attributed to the extraordinarily high uptake. The intracellular uptake of 6 was about 7.6 times higher than 1. In contrast, thiaporphyrin 8 with only two meso aryl groups was less effective as a photosensitizer, perhaps due to poorer uptake and a lower quantum yield for the generation of singlet oxygen.

The first tellurium-containing analogues of the rosamine and rhodamine dyes were prepared by the addition of Grignard or organolithium reagents to telluroxanthone precursors. The 125Te spectra of both the dyes and the telluroxanthone precursors are reported. One derivative was characterized by X-ray crystallography and was found to have a nearly planar telluroxanthylium core with a 9-aryl substituent held nearly orthogonal to the core. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed to analyze the trends for the excitation wavelengths observed experimentally. The computations indicated that participation of the heteroatom lone pair orbitals is responsible for this trend.

2,4-Bis(4-dimethylaminophenyl)-6-alkylthiopyrylium and selenopyrylium dyes are essentially nonfluorescent (phi F0.001) and are poor generators of singlet oxygen in aqueous solution. However, upon complexation to calf thymus DNA, quantum yields for both fluorescence and generation of singlet oxygen increased dramatically. Irradiation of the dye-DNA complexes produced strand breaks in the DNA. The photodamage is not observed in the absence of oxygen and is suppressed by the addition of the singlet oxygen quencher imidazole. The inactivation of the pseudo-rabies virus upon treatment of oxygenated leukodepleted 20% hematocrit red blood cell suspensions with the chalcogenopyrylium dyes and light followed the same trend observed with quantum yields for the generation of singlet oxygen in the dye-DNA complexes.

A series of thio- and selenopyrylium analogues of 2,4-di(4-dimethylaminophen-yl)-6-methylthiopyrylium iodide were prepared in five steps from 4-dimethylaminophenyl-propargyl aldehyde and the corresponding lithium acetylide. When bound to DNA, all of the dyes absorb at wavelengths >600 nm, which avoids the hemoglobin band I maximum at 575 nm. The binding of the series of dyes to double-stranded DNA was examined spectrophotometrically and by isothermal titration calorimetry to determine binding constants, by a topoisomerase I DNA unwinding assay, by competition dialysis with [poly(dGdC)] 2 and [poly(dAdT)] 2 , and by ethidium bromide displacement studies to examine propensities for intercalation, and by circular dichroism studies. The dyes were found to show mixed binding modes.