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Calcium ion (Ca 2+ ) control is an essential tool in neuronal research. Herein, we report three thiocoumarin-based, visible light-activated Ca 2+ chelators with quantum yields of 0.39, 0.52, and 0.83. The chelators demonstrated an over 10 5 -fold increase in Ca 2+ binding affinity upon irradiation. These chelators are efficiently triggered by biologically safer wavelengths, rendering them excellent candidates for use in neurological research and medicine.

Glutamate (Glu) is an excitatory neurotransmitter that plays a critical role in memory. Brain mapping activities of such pathways relied heavily on the ability to release Glu with spatiotemporal precision. Several photo-protecting groups (PPGs), referred to as photocages or cages, were designed to accomplish the release of Glu upon irradiation. Previously reported Glu cages responded to UV upon irradiation with single photons, which limited their use in vivo experiments due to cytotoxicity. Other caged designs suffered from lower quantum efficiency (QE) of release necessitating higher concentrations and/or longer photoirradiation times. There have been limited examples of cages that respond to visible light with single photon irradiation. Herein, we report the efficient preparation of 11 caged Glu examples that respond to two visible wavelengths, 467 nm (thiocoumarin based) and 515-540 nm (BODIPY based). The kinetics of photouncaging were studied for all caged designs, and we report all quantum efficiencies, i.e., quantum yields (Φ), that ranged from 0.0001-0.65. Two of the BODIPY cages are reported here for the first time, and one, Me-BODIPY-Br-Glu, shows the most efficient Glu release with a QE of 0.65. Similar caged designs can be extended to the inhibitory neurotransmitter, GABA. This would enable the use of two visible wavelengths to modulate the release of excitatory and inhibitory neurotransmitters upon demand via optical control., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Silver is a well-established antimicrobial agent. Conjugation of organic ligands with silver nanoparticles has been shown to create antimicrobial nanoparticles with improved pharmacodynamic properties and reduced toxicity. Twelve novel organic ligand functionalized silver nanoparticles (AgNPs) were prepared via a light-controlled reaction with derivatives of benzothiazole, benzoxazine, quinazolinone, 2-butyne-1,4-diol, 3-butyne-1-ol, and heptane-1,7-dioic. UV-vis, Fourier-transform infrared (FTIR) spectroscopy, and energy-dispersive X-ray (EDAX) analysis were used to confirm the successful formation of ligand-functionalized nanoparticles. Dynamic light scattering (DLS) revealed mean nanoparticle diameters between 25 and 278 nm. Spherical and nanotube-like morphologies were observed using transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Seven of the twelve nanoparticles exhibited strong antimicrobial activity and five of the twelve demonstrated significant antibacterial capabilities against E. coli in a zone-of-inhibition assay. The synthesis of functionalized silver nanoparticles such as the twelve presented is critical for the further development of silver-nanoconjugated antibacterial agents.

Solubility of growth regulators is essential for their use in agriculture. Four new cytokinin salts─6-benzylaminopurine mesylate ( 1 ), 6-(2-hydroxybenzylamino)purine mesylate ( 2 ), 6-(3-hydroxybenzylamino)purine mesylate ( 3 ), and 6-(3-methoxybenzylamino)purine mesylate ( 4 )─were synthesized, and their crystal structures were determined to clarify structural influence on water solubility. The mesylates were several orders of magnitude more water-soluble than the parent CKs. The new salts significantly reduced chlorophyll degradation and impairment of photosystem II functionality in barley leaf segments undergoing artificial senescence and had pronounced effects on the leaves' endogenous CK pools, maintaining high concentrations of functional metabolites for several days, unlike canonical CKs. A foliar treatment with 1 and 3 increased the harvest yield of spring barley by up to 8% when compared to treatment with the parent CKs while also increasing the number of productive tillers. This effect was attributed to the higher bioavailability of the mesylate salts and the avoidance of dimethyl sulfoxide exposure.

Imidacloprid (IMI), an emerging pollutant, has high toxicity to non-target organisms. This paper presents the kinetics of IMI removal by ferrate(VI) at different pH (6.0-9.0), molar ratios ([ferrate(VI)]:[IMI]) and added Fe(III) ions. The apparent second-order rate constant (k app ) decreased with increase in pH from pH 6.0 to 9.0 (i.e., (1.2 ± 0.1) × 10 2  M -1  s -1 to (8.3 ± 0.3) M -1  s -1 ). The species-specific rate constants were obtained as k (HFeO 4 - ) = 1.3 × 10 2  M -1  s -1 and k (FeO 4 2- ) = 6.9 M -1  s -1 . The decreases in the concentration of HFeO 4 - with increase in pH caused the observed pH dependence in k app . At pH 7.0, the removal of IMI increased with the molar ratio from 1.0 to 10.0 with complete removal at the highest ratio. The variation in pH from 6.0 to 9.0 had no obvious effect on removal of IMI. Experiments indicate that IMI removal is mainly by ferrate(VI) oxidation and to a lesser extent by Fe(III) adsorption. Mineralization of IMI was also observed (20-26%). The addition of Fe(III) ions to ferrate(VI)-IMI at pH 7.0 and 8.0 resulted in enhanced removal of IMI, but the presence of Ca 2+ , SO 4 2- , HCO 3 - , and humic acid (HA) has negative effects. The presence of coexisting substances in river water slightly decreased IMI removal by ferrate(VI) by less than 10%. Identification of products and frontier electron density (FED) calculations demonstrated involvement of opening of the five-membered heterocyclic moiety of IMI by ferrate(VI). Toxicity assessment with NIH 3T3 fibroblasts and ECOSAR analysis indicated lower toxicity of oxidized products than parent IMI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Many bacteria, such as Pseudomonas aeruginosa, regulate phenotypic switching in a population density-dependent manner through a phenomenon known as quorum sensing (QS). For Gram-negative bacteria, QS relies on the synthesis, transmission, and perception of low-molecular-weight signal molecules that are predominantly N-acyl-l-homoserine lactones (AHLs). Efforts to disrupt AHL-mediated QS have largely focused on the development of synthetic AHL analogues (SAHLAs) that are structurally similar to native AHLs. However, like AHLs, these molecules tend to be hydrophobic and are poorly soluble under aqueous conditions. Water-soluble macrocycles, such as cyclodextrins (CDs), that encapsulate hydrophobic guests have long been used by both the agricultural and pharmaceutical industries to overcome the solubility issues associated with hydrophobic compounds of interest. Conveniently, CDs have also demonstrated anti-AHL-mediated QS effects. Here, using fluorescence spectroscopy, NMR spectrometry, and mass spectrometry, we evaluate the affinity of SAHLAs, as well as their hydrolysis products, for β-CD inclusion. We also evaluated the ability of these complexes to inhibit wild-type P. aeruginosa virulence in a Caenorhabditis elegans host infection study, for the first time. Our efforts confirm the potential of β-CDs for the improved delivery of SAHLAs at the host/microbial interface, expanding the utility of this approach as a strategy for probing and controlling QS., (© 2020 Wiley-VCH GmbH.)

The 7-nitroindolinyl family of caging chromophores has received much attention in the past two decades. However, its uncaging mechanism is still not clearly understood. In this study, we performed state-of-the-art density functional theory calculations to unravel the photo-uncaging mechanism in its entirety, and we compared the probabilities of all plausible pathways. We found competition between a classical cyclization and an acyl migration pathway, and here we explain the electronic and steric reasons behind such competition. The migration mechanism possesses the characteristics of a combined Norrish type I and a 1,6-nitro-acyl variation of a Norrish type II mechanism, which is reported here for the first time. We also found negligible energetic differences in the uncaging mechanisms of the 4-methoxy-5,7-dinitroindolinyl (MDNI) cages and their mononitro analogues (MNI). We traced the experimentally observed improved quantum yields of MDNI to a higher population of the reactants in the triplet surface. This fact is supported by a more favorable intersystem crossing due to the availability of a higher number of triplet excited states with the correct symmetry in MDNI than in MNI. Our findings may pave the way for improved cage designs that possess higher quantum yields and a more efficient agonist release.

This paper investigated the oxidation of recalcitrant micropollutants [i.e., atenolol (ATL), flumequine, aspartame, and diatrizoic acid] by combining ferrate(VI) (Fe VI O 4 2- , Fe VI ) with a series of metal ions [i.e., Fe(III), Ca(II), Al(III), Sc(III), Co(II), and Ni(II)]. An addition of Fe(III) to Fe VI enhanced the oxidation of micropollutants compared solely to Fe VI . The enhanced oxidation of studied micropollutants increased with increasing [Fe(III)]/[Fe VI ] to 2.0. The complete conversion of phenyl methyl sulfoxide (PMSO), as a probe agent, to phenyl methyl sulfone (PMSO 2 ) by the Fe VI -Fe(III) system suggested that the highly reactive intermediate Fe IV /Fe V species causes the increased oxidation of all four micropollutants. A kinetic modeling of the oxidation of ATL demonstrated that the major species causing the increase in ATL removal was Fe IV , which had an estimated rate constant as (6.3 ± 0.2) × 10 4 M -1 s -1 , much higher than that of Fe VI [(5.0 ± 0.4) × 10 -1 M -1 s -1 ]. Mechanisms of the formed oxidation products of ATL by Fe IV , which included aromatic and/or benzylic oxidation, are delineated. The presence of natural organic matter significantly inhibited the removal of four pollutants by the Fe VI -Fe(III) system. The enhanced effect of the Fe VI -Fe(III) system was also seen in the oxidation of the micropollutants in river water and lake water.

An efficient strategy for N/O-(deutero)alkylation of indoles and phenols with alkoxides/alcohols as the alkylation reagents is described. The consecutive detosylation/alkylation transformations feature mild reaction conditions, high ipso -selectivity, and good functional group tolerance (>50 examples). A one-pot selective N-alkylation of unprotected indoles with alcohols and TsCl is also realized. The application of this method is demonstrated by the introduction of isotope-labeled (CD 3 and 13 CH 3 ) groups using the readily accessible labeled alcohols and the synthesis of pharmaceuticals.

Organocatalysis is an emerging field, in which small metal-free organic structures catalyze a diversity of reactions with a remarkable stereoselectivity. The ability to selectively switch on such pathways upon demand has proven to be a valuable tool in biological systems. Light as a trigger provides the ultimate spatial and temporal control of activation. However, there have been limited examples of phototriggered catalytic systems. Herein, we describe the synthesis and application of a caged proline system that can initiate organocatalysis upon irradiation. The caged proline was generated using the highly efficient 4-carboxy-5,7-dinitroindolinyl (CDNI) photocleavable protecting group in a four-step synthesis. Advantages of this system include water solubility, biocompatibility, high quantum yield for catalyst release, and responsiveness to two-photon excitation. We showed the light-triggered catalysis of a crossed aldol reaction, a Mannich reaction, and a self-aldol condensation reaction. We also demonstrated light-initiated catalysis, leading to the formation of a biocide in situ, which resulted in the growth inhibition of E. coli, with as little as 3 min of irradiation. This technique can be broadly applied to other systems, by which the formation of active forms of drugs can be catalytically assembled remotely via two-photon irradiation.

This work presents ferrate(VI) (Fe VI O 4 2- , Fe VI ) oxidation of a wide range of sulfonamide antibiotics (SAs) containing five- and six-membered heterocyclic moieties ( R) in their molecular structures. Kinetics measurements of the reactions between Fe VI and SAs at different pH (6.5-10.0) give species-specific second-order rate constants, k 5 and k 6 of the reactions of protonated Fe VI (HFeO 4 - ) and unprotonated Fe VI (Fe VI O 4 2- ) with protonated SAs (HX), respectively. The values of k 5 varied from (1.2 ± 0.1) × 10 3 to (2.2 ± 0.2) × 10 4 M -1 s -1 , while the range of k 6 was from (1.1 ± 0.1) × 10 2 to (1.0 ± 0.1) × 10 3 M -1 s -1 for different SAs. The transformation products of reaction between Fe VI and sulfadiazine (SDZ, contains a six-membered R) include SO 2 extrusion oxidized products (OPs) and aniline hydroxylated products. Comparatively, oxidation of sulfisoxazole (SIZ, a five-membered R) by Fe VI has OPs that have no SO 2 extrusion in their structures. Density functional theory calculations are performed to demonstrate SO 2 extrusion in oxidation of SDZ by Fe VI . The detailed mechanisms of oxidation are proposed to describe the differences in the oxidation of six- and five-membered heterocyclic moieties ( R) containing SAs (i.e., SDZ versus SIZ) by Fe VI .

We report the synthesis of 9-CD 3 -9- cis -retinal via a six-step procedure from β-ionone. The steps involve an initial deuteration of the methyl ketone of β-ionone followed by two consecutive Horner-Wadsworth-Emmons (HWE) coupling reactions and their corresponding DIBAL reductions. A final oxidation of the allylic alcohol of the retinol leads to the target compound. This deuterium labeled retinoid is an important cofactor for studying protein-retinoid interactions in isorhodopsin.

Glutamate is an excitatory neurotransmitter that controls numerous pathways in the brain. Neuroscientists make use of photoremovable protecting groups, also known as cages, to release glutamate with precise spatial and temporal control. Various cage designs have been developed and among the most effective has been the nitroindolinyl caging of glutamate. We, hereby, report an improved synthesis of one of the current leading molecules of caged glutamate, 4-carboxymethoxy-5,7-dinitroindolinyl glutamate (CDNI-Glu), which possesses efficiencies with the highest reported quantum yield of at least 0.5. We present the shortest route, to date, for the synthesis of CDNI-Glu in 4 steps, with a total reaction time of 40 h and an overall yield of 20%. We also caged glutamate at the other two functional groups, thereby, introducing two new cage designs: α-CDNI-Glu and N-CDNI-Glu. We included a study of their photocleavage properties using UV-vis, NMR, as well as a physiology experiment of a two-photon uncaging of CDNI-Glu in acute hippocampal brain slices. The newly introduced cage designs may have the potential to minimize the interference that CDNI-Glu has with the GABA A receptor. We are broadly disseminating this to enable neuroscientists to use these photoactivatable tools.

This paper presents oxidation of polychlorinated diphenyl sulfides (PCDPSs), dioxin-like compounds, by ferrate(VI) (Fe VI O 4 2- , Fe(VI)). Kinetics of the reactions of Fe(VI) with seventeen PCDPSs, differ in number and positions of chlorine atoms (from 2 to 7), were investigated at pH 8.0. The second-order rate constants (k, M -1 s -1 ) of the reactions varied with the numbers and positions of chlorine atoms and appeared to be related with standard Gibbs free energy of formation (Δ f G 0 ) of PCDPSs. Degradation experiments in the presence of ions and humic acid demonstrated complete removal of PeCDPS by Fe(VI) in minutes. Pathways of the reaction were investigated by identifying oxidized products (OPs) of the reaction between Fe(VI) and 2,2',3',4,5-pentachlorodiphenyl sulfide (PeCDPS) at pH 8.0. Pathways of oxidation involved major pathway of attack on sulfur(II) by Fe(VI) in steps to yield sulfoxide type products, and subsequent breakage of C-S bond with the formation of sulfonic acid-containing trichloro compound. Minor pathways were hydroxylation of benzene ring and substitution of chlorine atom with hydroxyl group. Estimation of toxicity of OPs of the oxidation of PeCDPS by Fe(VI) suggested the decreased toxicity from the parent contaminant., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In this study we demonstrate the use of Direct Analysis in Real Time Mass Spectrometry (DART) as a powerful tool for detection of nonoxynol in vaginal fluid post contact with a condom, enabling rapid tracing and added evidences in sexual assault crimes. Vaginal fluid was sampled using cotton swabs and glass rods and measured directly with DART. Sample preparation using water, hexane, methanol, and dichloromethane extraction, was explored for comparison and optimization of signals. Nonoxynol was detected up to eight hours after sampling. Optimal sampling conditions and mass spectrometry parameters are reported and discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We recently reported a new method for the direct dehydrogenative C-H silylation of heteroaromatics utilizing Earth-abundant potassium tert-butoxide. Herein we report a systematic experimental and computational mechanistic investigation of this transformation. Our experimental results are consistent with a radical chain mechanism. A trialkylsilyl radical may be initially generated by homolytic cleavage of a weakened Si-H bond of a hypercoordinated silicon species as detected by IR, or by traces of oxygen which can generate a reactive peroxide by reaction with [KOt-Bu] 4 as indicated by density functional theory (DFT) calculations. Radical clock and kinetic isotope experiments support a mechanism in which the C-Si bond is formed through silyl radical addition to the heterocycle followed by subsequent β-hydrogen scission. DFT calculations reveal a reasonable energy profile for a radical mechanism and support the experimentally observed regioselectivity. The silylation reaction is shown to be reversible, with an equilibrium favoring products due to the generation of H 2 gas. In situ NMR experiments with deuterated substrates show that H 2 is formed by a cross-dehydrogenative mechanism. The stereochemical course at the silicon center was investigated utilizing a 2 H-labeled silolane probe; complete scrambling at the silicon center was observed, consistent with a number of possible radical intermediates or hypercoordinate silicates.

A two-step stereoselective preparation of a goldfish pheromone, 17α,20β-dihydroxy-4-pregnen-3-one, is reported from the readily available cortexolone in 64% overall yield. The (20S)-epimer was also synthesized in three steps from cortexolone with an overall yield of 47%. A microscale chiroptical technique based on a host/guest complexation mechanism between the substrate and a dimeric metalloporphyrin host (tweezer) was used to confirm the stereochemical assignment, while Density Functional Theory (DFT) calculations were employed to explain the high stereoselectivity induced by the 17α-hydroxyl and C18-methyl groups., (© 2013 Wiley Periodicals, Inc.)

The kinetics of the oxidation of sucralose, an emerging contaminant, and related monosaccharides and disaccharides by ferrate(VI) (Fe(VI)) were studied as a function of pH (6.5-10.1) at 25°C. Reducing sugars (glucose, fructose, and maltose) reacted faster with Fe(VI) than did the non-reducing sugar sucrose or its chlorinated derivative, sucralose. Second-order rate constants of the reactions of Fe(VI) with sucralose and disaccharides decreased with an increase in pH. The pH dependence was modeled by considering the reactivity of species of Fe(VI), (HFeO(4)(-) and FeO(4)(2-)) with the studied substrates. Second-order rate constants for the reaction of Fe(VI) with monosaccharides displayed an unusual variation with pH and were explained by considering the involvement of hydroxide in catalyzing the ring opening of the cyclic form of the carbohydrate at increased pH. The rate constants for the reactions of carbohydrates with Fe(VI) were compared with those for other oxidant species used in water treatment and were briefly discussed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The root bark of Cassia sieberiana was analyzed using direct analysis in real time mass spectrometry, and a main flavonoid component with an [M + H](+) mass of 275 was identified. The flavonoid, epiafzelechin, was isolated and fully characterized with the concerted use of NMR spectroscopy, circular dichroism, and optical rotation. Electronic circular dichroism and optical rotation TDDFT calculations were also performed, and their agreement with the experimental results confirmed the enantiomeric identity of the isolated natural product. The antioxidant activity of the compound was also investigated.

Sulfonamide antimicrobials are used in both human therapy and animal husbandry. Sulfonamides are not readily biodegradable and have been detected in surface water and in secondary wastewater effluents. The chemical oxidation of sulfonamides by an environmentally friendly oxidant, ferrate(VI) (Fe(VI)O4(2-), Fe(VI)), was conducted. The sulfonamides used in the oxidation studies were sulfisoxazole, sulfamethazine, sulfamethizole, sulfadimethoxine, and sulfamethoxazole. Kinetics of the reactions were determined as a function of pH (7.0-9.7) and temperature (15-45 degrees C) by a stopped-flow technique. The rate law for the oxidation of sulfonamides by Fe(VI) is first-order with respect to each reactant. The observed second-order rate constants decreased nonlinearly with an increase in pH and are possibly related to the protonation of Fe(VI) (HFeO4- <==> H+ + FeO4(2-); pK(a,HFeO4) = 7.23) and sulfonamides (SH <==> H+ + S-; pK(a,SH) = 5.0-7.4). The activation parameters of the reactions vary with pH due to temperature dependence on the protonation of Fe(VI) and sulfonamides. These results were used to obtain enthalpy of dissociation of sulfonamides. Stoichiometry and products of sulfamethoxazole (SMX) reactions with Fe(VI) were studied in detail using various analytical techniques to evaluate the effect of the oxidation process on the fate of sulfonamides in water. At a stoichiometric ratio of 4:1 (Fe(VI): SMX), complete removal of SMX was achieved. Analyses of oxidation products of the reaction as well as kinetic measurements of substructural models of SMX suggest that the attack of Fe(VI) occurs at the isoxazole moiety as well as at the aniline moiety with minimal preference. The results of the studies reported suggest that Fe(VI) has the potential to serve as a chemical oxidant for removing sulfonamides and converting them to relatively less toxic byproducts in water.

Aluminumoxyhydride (HAlO) has been obtained by the reaction of aluminum hydride with the siloxane (Me2HSi)2O or the stannoxane (Bu3Sn)2O as an amorphous colorless insoluble powder. The highest-purity product resulted from the reaction of H3Al.NMe3 with (Me2HSi)2O. However, HAlO suspensions in tetrahydrofuran (THF) of sufficient quality for synthetic applications can be prepared from commercially available reagents with only minor precautions. A LiAlH4 solution in THF was treated successively with Me3SiCl and (Me2HSi)2O, followed by heating at 60 degrees C for 20 h. The resulting suspensions are 0.4-0.5 M in active hydride content and selectively reduce aldehydes and ketones to the respective alcohols in the presence of any other common nonprotic functional group.

All trans retinal was attached to both the primary face and the secondary face of beta-cyclodextrin via a Schiff base linkage, analogous to that in rhodopsin. The new models were evaluated and compared with n-butylamine retinylidene Schiff base for their rates of hydrolysis, and factors that influence such rates. Competition studies using adamantane carboxylate demonstrated the kinetic trap theory by diminishing the binding of retinal in the cyclodextrin, thereby augmenting the rate of hydrolysis. NMR experiments indicate that the retinylidene is most probably bound in the form of a dimer.

Retinal pigment epithelial (RPE) membranes contain the full biochemical apparatus capable of processing all-trans-retinol (vitamin A) into 11-cis-retinal, the visual chromophore. As many of these proteins are integral membrane proteins and resistant to traditional methods of identification, alternate methods of identifying these proteins are sought. The approach described here involves affinity biotinylation with alkali cleavable linkers. A vitamin A containing affinity-labeling haloacetate is described which facilitates the identification of retinoid binding proteins (RBPs). Treatment of crude bovine RPE membranes with (3R)-3-[boc-lys(biotinyl)-O]-all-trans-retinol chloroacetate 1 in the low micromolar range led to the specific labeling of RPE65 and lecithin retinol acyltransferase (LRAT). Only RPE65 is labeled at 5 microM 1 at 4 degrees C. Labeled RPE65 was readily isolated by binding the labeled protein to avidin-containing beads, followed by cleavage of the protein from the beads at pH 11. Trypsin digestion of RPE65 modified by 1, followed by mass spectrometry, demonstrates that C231 and C448 are alkylated by 1. These studies validate the approach that was used, and furthermore demonstrate that RPE65, a major membrane-associated protein of the RPE, is a RBP.

Heterologous proteins capable of transducing physical or chemical stimuli into electrical signals can be used to control the function of excitable cells in intact tissues or organisms. Restricted genetically to circumscribed populations of cellular targets, these selectively addressable sources of depolarizing current can supply distributed inputs to neural circuits, stimulate secretion, or regulate force and motility. In an initial demonstration of this principle, we have used elements of a G protein coupled signaling system, the phototransduction cascade of the fruit fly, to sensitize generalist vertebrate neurons to light [Zemelman, B. V., Lee, G. A., Ng, M. & Miesenböck, G. (2002) Neuron 33, 15-22]. We now describe the use of ectopically expressed ligand-gated ion channels as transducers of optical or pharmacological stimuli. When either the capsaicin receptor, TRPV1, the menthol receptor, TRPM8, or the ionotropic purinergic receptor P2X(2) was introduced into hippocampal neurons, the cells responded to pulsed applications of agonist with characteristic sequences of depolarization, spiking, and repolarization. Responses required cognate matches between receptor and agonist, peaked at firing frequencies of approximately 40 Hz, initiated and terminated rapidly, and did not attenuate. Precise dose-response relationships allowed current amplitudes and firing frequencies to be tuned by varying the concentration of ligand. Agonist could be administered either pharmacologically or, in the cases of TRPV1 and P2X(2), optically, through photorelease of the active compounds from the respective "caged" precursors, 4,5-dimethoxy-2-nitrobenzyl-capsaicin and P(3)-[1-(4,5-dimethoxy-2-nitrophenyl)ethyl]-ATP.

A structural study of complexes formed between a dimeric zinc porphyrin tweezer (host) and chiral monoalcohols and monoamines derivatized by a bidentate carrier molecule (guest) confirmed that their CD couplets arise from the preferred porphyrin helicity of 1:1 host-guest complexes. NMR experiments and molecular modeling of selected tweezer complexes revealed that the preferred conformation is the one in which the L (larger) group protrudes from the porphyrin sandwich; this preferred helicity of the complex determines the CD of the complexes. It was found that the porphyrin ring-current induced (1)H chemical shifts and molecular modeling studies of the complex lead to the assignments of relative steric size of the L (large)/M (medium) substituents attached to the stereogenic center. The assignments, in turn, are correlated with the sign of the CD exciton couplet that establishes the absolute configuration at the stereogenic center. Variable-temperature NMR experiments proved that the observed increase in CD amplitude at lower temperatures derives from conformational changes in the preferred offset geometry between two porphyrin rings.

A general microscale protocol for the determination of absolute configurations of primary amino groups or secondary hydroxyl groups linked to a single stereogenic center is described. The chiral substrates are linked to the achiral trifunctional bidentate carrier molecule (3-aminopropylamino)acetic acid (1, H(2)NCH(2)CH(2)CH(2)NHCH(2)COOH) and the resultant conjugates are then complexed with dimeric zinc porphyrin host 2 giving rise to 1:1 host/guest sandwiched complexes. These complexes exhibit exciton-coupled bisignate CD spectra due to stereodifferentiation leading to preferred porphyrin helicity. Since the chiral sense of twist between the two porphyrins in the complex is dictated by the stereogenic center of the substrate, the sign of the couplet determines the absolute configuration at this center. The twist of the porphyrin tweezer in the complex can be predicted from the relative steric sizes of the groups flanking the stereogenic center, such that the bulkier group protrudes from the complex sandwich. In certain alpha-hydroxy esters and alpha-amino esters, electronic factors and hydrogen bonding govern the preferred conformation of the complex, and hence the CD spectra.