Ring-opened Form Research Articles

Photoelectric conversion based on proton-coupled electron transfer reactions.

Making efficient use of solar energy is one of the biggest challenges of our time. In nature, solar energy can be harvested by photosynthesis where proton-coupled electron transfer (PCET) plays a critical role. Here, PCET is utilized for the first time to directly convert light energy to electrical energy. Quinone/hydroquinone PCET redox couples were used to produce a photovoltage along with spiropyrans, photoswitchable compounds that undergo reversible transformation between a ring-closed (Sp) and ring-opened form (Mc). The Mc form is more basic than the Sp form, and the open-circuit voltage (V(oc)) is related to the proton concentration and that of the Sp/Mc ratio controlled by light. V(oc) values from 100 to 140 mV were produced. In addition to direct current (J(sc) ca. 9 μA cm(-2)), alternating current in the range of 0.1 to 200 Hz was also produced by manipulating the input light.

Spiropyran-Modified Gold Nanoparticles: Reversible Size Control of Aggregates by UV and Visible Light Irradiations

UV or visible light irradiation of gold nanoparticles (AuNPs) modified with a thiol-terminated spiropyran dye promotes reversible aggregation or dispersion of AuNPs. This is facilitated by the electrostatic repulsion/attraction between the AuNPs controlled by the ring-opening/closing photoisomerization of the surface dyes. This photochemical method successfully produces aggregates of AuNPs with tunable sizes (20-340 nm) and narrow size distributions (standard deviation <34%) in a reversible manner. In addition, the formed aggregates, even when left in the dark condition, scarcely change their sizes because the stacking interaction between the ring-opened forms of surface dyes suppresses thermal reverse isomerization and maintains the attractive force between the AuNPs.

Design and Synthesis of Novel Rhodamine-based Chemosensor Probe Toward Cu2+Cation

Nowdays, fluorescent rhodamine chemosensors have attracted a worldwide interest due to its ability to selectively detect heavy and transition metal cations. Due to the importance in environmental and biological toxic effects, the developments of fluorescent chemosensors have been received considerable attention in recent. Especially, a rhodamine-based chemosensor probes have been proved to be useful by exhibiting the efficient “off-on” fluorescence switching toward selected metal cations. This fluorophore can undergo the transformation from non-fluorescent and colorless spirolactam derivative to fluorescent ring-open form. In this study, a new fluorescent chemosensor was synthesized using rhodamine B through two-step procedures, and its selectivity and related optical property were characterized. Selectivity and sensitivity was found toward Cu 2+ guest molecules and then related optical properties of rhodamine B based fluorescent chemosensor compound were characterized using discussed. In addition, computational calculation was used to determine the HOMO/LUMO values.

Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

Photochromic cholinesterase inhibitors were obtained from cis-1,2-α-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target compounds are potent acetyl- (AChE) and butyrylcholinesterase (BChE) inhibitors in the nanomolar concentration range. Compound 11b bearing an octylene linker exhibited interactions with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Yet upon irradiation with light, the mechanism of interaction varied from one photochromic form to another, which was investigated by kinetic studies and proved "photoswitchable". The AChE-induced β-amyloid (Aβ) aggregation assay gave further experimental support to this finding: Aβ1-40 aggregation catalyzed by the PAS of AChE might be inhibited by compound 11b in a concentration-dependent manner and seems to occur only with one photochromic form. Computational docking studies provided potential binding modes of the compound. Docking studies and molecular dynamics (MD) simulations for the ring-open and -closed form indicate a difference in binding. Although both forms can interact with the PAS, more stable interactions are observed for the ring-open form based upon stabilization of a water molecule network within the enzyme, whereas the ring-closed form lacks the required conformational flexibility for an analogous binding mode. The photoswitchable inhibitor identified might serve as valuable molecular tool to investigate the different biological properties of AChE as well as its role in pathogenesis of AD in in vitro assays.

Light-Controlled Reversible Release and Uptake of Potassium Ions from Ion-Exchanging Nanospheres

Here, we report for the first time on photoswitchable nanospheres containing spiropyran (Sp) for reversible release and uptake of metal ions. K(+) is used as a model ion to demonstrate the chemical principle of this approach. Valinomycin is incorporated in the nanospheres to stabilize K(+). Upon UV illumination, Sp transforms to the more basic ring-opened merocyanine form, which takes up H(+) from the surrounding aqueous solution and expels K(+) from the nanospheres. The process can be reversed by irradiation with visible light to reduce the surrounding K(+) concentration.

Reversible Photochromic System Based on Rhodamine B Salicylaldehyde Hydrazone Metal Complex

Photochromic molecules are widely applied in chemistry, physics, biology, and materials science. Although a few photochromic systems have been developed before, their applications are still limited by complicated synthesis, low fatigue resistance, or incomplete light conversion. Rhodamine is a class of dyes with excellent optical properties including long-wavelength absorption, large absorption coefficient, and high photostability in its ring-open form. It is an ideal chromophore for the development of new photochromic systems. However, known photochromic rhodamine derivatives, such as amides, exhibit only millisecond lifetimes in their colored ring-open forms, making their application very limited and difficult. In this work, rhodamine B salicylaldehyde hydrazone metal complex was found to undergo intramolecular ring-open reactions upon UV irradiation, which led to a distinct color and fluorescence change both in solution and in solid matrix. The complex showed good fatigue resistance for the reversible photochromism and long lifetime for the ring-open state. Interestingly, the thermal bleaching rate was tunable by using different metal ions, temperatures, solvents, and chemical substitutions. It was proposed that UV light promoted isomerization of the rhodamine B derivative from enol-form to keto-form, which induced ring-opening of the rhodamine spirolactam in the complex to generate color. The photochromic system was successfully applied for photoprinting and UV strength measurement in the solid state. As compared to other reported photochromic molecules, the system in this study has its advantages of facile synthesis and tunable thermal bleaching rate, and also provides new insights into the development of photochromic materials based on metal complex and spirolactam-containing dyes.

Evidence That GH115 α-Glucuronidase Activity, Which Is Required to Degrade Plant Biomass, Is Dependent on Conformational Flexibility

The microbial degradation of the plant cell wall is an important biological process that is highly relevant to environmentally significant industries such as the bioenergy and biorefining sectors. A major component of the wall is glucuronoxylan, a β1,4-linked xylose polysaccharide that is decorated with α-linked glucuronic and/or methylglucuronic acid (GlcA/MeGlcA). Recently three members of a glycoside hydrolase family, GH115, were shown to hydrolyze MeGlcA side chains from the internal regions of xylan, an activity that has not previously been described. Here we show that a dominant member of the human microbiota, Bacteroides ovatus, contains a GH115 enzyme, BoAgu115A, which displays glucuronoxylan α-(4-O-methyl)-glucuronidase activity. The enzyme is significantly more active against substrates in which the xylose decorated with GlcA/MeGlcA is flanked by one or more xylose residues. The crystal structure of BoAgu115A revealed a four-domain protein in which the active site, comprising a pocket that abuts a cleft-like structure, is housed in the second domain that adopts a TIM barrel-fold. The third domain, a five-helical bundle, and the C-terminal β-sandwich domain make inter-chain contacts leading to protein dimerization. Informed by the structure of the enzyme in complex with GlcA in its open ring form, in conjunction with mutagenesis studies, the potential substrate binding and catalytically significant amino acids were identified. Based on the catalytic importance of residues located on a highly flexible loop, the enzyme is required to undergo a substantial conformational change to form a productive Michaelis complex with glucuronoxylan.

Switching light with light – advanced functional colloidal monolayers

Colloidal monolayers comprising of highly ordered two dimensional crystals are of high interest to generate surface patterns for a variety of different applications. Mostly, unfunctionalized polymer or silica colloids are assembled into monolayers. However, the incorporation of functional molecules into such colloids offers a convenient possibility of implementing additional properties to the two-dimensional crystal. Here, we present the formation of novel functional colloidal monolayers with photoswitchable fluorescence. The miniemulsion polymerization technique was used to incorporate an appropriate dye system of a perylene-based fluorophore and a bis-arylethene as a photochrome in polymeric colloids in defined ratios. Upon irradiation with UV or visible light the photochrome reversibly isomerizes from the ring-closed form, which is able to absorb light of the emission wavelength of the fluorescent dye and the ring-open form, which is not. The fluorescence emission of the dye can thus be reversibly switched on and off with light even when embedded in colloids. The colloids were self-assembled at the air-water interface to produce hexagonally ordered functional monolayers and more complex binary crystals. We investigate in detail the influence of the polymeric matrix on the switching properties of the fluorophore/photochrome system and find that the rate constants for the photoswitching, which all lie in the same range, are less influenced by the polymeric environment than expected. We demonstrate the reversible switching of the fluorescence emission in self-assembled colloidal monolayers. The arrangement of broadly distributed functional colloids into ordered monolayers with high addressability was obtained by the formation of binary colloidal monolayers.

From iridoids to dyes: a theoretical study on genipin reactivity

A mechanistic theoretical study of the reaction between methylamine and genipin, an iridoid obtained from some natural sources, is here presented. Starting from the opening of the genipin six-membered ring experimentally hypothesized and proved in our previous theoretical work, methylamine reaction with the three different forms of genipin in equilibrium has been studied in terms of activation enthalpies and product stabilization. The kinetically favored reaction pathways, initiated by the attack of the amine on the carbonyl groups of the dialdehydic open-ring form of genipin, have been then studied until the formation of the first orange/red product. The catalytic role of a few water molecules has been clearly shown for many reactions in the process and a fundamental redox autocatalytic cycle has been proposed for the formation of the orange/red product. This mechanism explains well the experimental evidence previously reported in literature. 1H-NMR and UV-visible spectra have been reproduced for each stable intermediate of the process.

The first structural and spectroscopic characterisation of a ring-opened form of a 2H-naphtho[1,2-b]pyran: a novel photomerocyanine.

Heating 4-methoxy-1-naphthol with a 1,1-diarylprop-2-yn-1-ol gave the 2,2-diaryl-6-methoxy-2H-naphtho[1,2-b]pyran together with the novel merocyanine, (E)-2-[3',3'-bis(aryl)allylidene]-4-methoxynaphthalen-1(2H)-one. Brief UV-irradiation of the pyran favoured the formation of the (Z)-merocyanine with longer irradiation and/or acidic conditions favouring the (E)-isomer.

Atropisomerization inN-aryl-2(1H)-pyrimidin-(thi)ones: A Ring-Opening/Rotation/Ring-Closure Process in Place of a Classical Rotation around the Pivot Bond

Uncatalyzed racemization processes in atropisomeric diphenyl-like frameworks are classically described as the result of the rotation around the pivotal single bond linking two planar frameworks. Severe constraints leading to more or less distorted transition states account for the experimental barrier to atropenantiomerization. In 1988, one of us hypothesized that, in N-aryl-2(1H)-pyrimidin-(thi)ones, a ring-opening/ring-closure process was contributing to the observed racemization process accounting for the lower barriers in the sulfur analogues than in oxygen analogues. Now, a series of six novel 6-amino-5-cyano-1,4-disubstituted-2(1H)-pyrimidinones 5a-5f and two 6-amino-5-cyano-4-p-tolyl-1-substituted-2(1H)-pyrimidinethiones 6a and 6b were synthesized and characterized through spectroscopic and X-ray diffraction studies. Semipreparative HPLC chiral separation was achieved, and enantiomerization barriers were obtained by thermal racemization. The rotational barriers of 6-amino-5-cyano-1-o-tolyl-4-p-tolyl-2(1H)-pyrimidinone (5b) and 6-amino-5-cyano-1-(naphthalen-1-yl)-4-p-tolyl-2(1H)-pyrimidinone (5e) were found to be 120.4 and 125.1 kJ·mol(-1) (n-BuOH, 117 °C), respectively, and those of the corresponding thiones were 116.8 and 109.6 kJ·mol(-1) (EtOH, 78 °C), respectively. DFT calculations of the rotational barriers clearly ruled out the classical rotation around the pivotal bond with distorted transition states in the case of the sulfur derivatives. Instead, the ranking of the experimental barriers (sulfur versus oxygen, and o-tolyl versus 1-naphthyl in both series) was nicely reproduced by calculations when the rotation occurred via a ring-opened form in N-aryl-2(1H)-pyrimidinethiones.

In vitro and in vivo metabolism of a novel chymase inhibitor, SUN13834, and the predictability of human metabolism using mice with humanized liver

1. A novel oral chymase inhibitor, SUN13834, is under clinical development for the treatment of atopic dermatitis (AD). In this study, in vitro and in vivo metabolic profiles of SUN13834 were compared between severe combined immunodeficiency (SCID) mice, chimeric mice with humanized liver and humans.2. In in vitro experiments using liver microsomes, predominant metabolites of SUN13834 were glucuronide (MG-1) in SCID mice and hydroxylated metabolite (M-3) in chimeric mice and humans.3. After a single oral dose of [14C]SUN13834 to SCID and chimeric mice, glucuronidation was the major metabolic pathway in SCID mice, while the parent compound, ring opening form (M-5), O-demethylated form of M-5 (M-6) and glucuronidation of M-6 (M-6G) were detected at higher levels in chimeric mice compared to SCID mice.4. When AD patients were orally treated using SUN13834 for 28 days, the parent compound had the highest concentration in plasma, and M-6, M-6G, M-5 and MG-1 were identified as major metabolites.5. This is the first report of SUN13834 metabolic information in human. In addition, based on similarities in metabolic profiles between chimeric mice and humans, it was concluded that chimeric mice are useful for predicting SUN13834 metabolism in humans during early stages of drug development.

A per-acetyl glycosyl rhodamine as a novel fluorescent ratiometric probe for mercury (II)

This paper describes the identification of a per-acetyl glycosyl rhodamine B (RB) derivative, KB2, simply prepared by a click reaction, as a novel fluorescent ratiometric probe for mercury (II). In an 80% aqueous solution, KB2 responded to Hg2+ in a ratiometric manner with a good selectivity over a range of metal cations. Upon formation of a 1:1 probe-ion complex, the blue fluorescence of the per-acetyl glycosyl moiety of KB2 is quenched, along with the emergence of a bright red fluorescence attributable to the lactam ring-opening form of RB. This is probably caused by a fluorescence resonance energy transfer from the acetyl glycoside as a donor to the acceptor RB–Hg2+ motif. This study provides unique insight into the design of ratiometric chemoprobes for heavy metals based on the simple coupling of per-acetyl glycosides with fluorogenic dyes.

The role of pH and ring-opening hydrolysis kinetics on liposomal release of topotecan

The use of liposomal delivery systems for the treatment of cancer has been extensively researched because of their passive targeting to the vasculature of solid tumors. While their potential to provide prolonged retention and high drug encapsulation is desirable for anticancer agents, a mechanistic understanding is required to optimize and design liposomal drug delivery systems capable of controllable release tailored to tumor type and patient. Topotecan (TPT) is a topoisomerase I inhibitor that undergoes reversible, pH-sensitive ring-opening hydrolysis. TPT may benefit from liposomal formulation using active loading strategies to generate low intravesicular pH to prolong drug retention and increase drug encapsulation. This paper develops a mathematical model to describe TPT's permeability as a function of pH by accounting for the drug's ionization state, membrane binding, and ring-opening interconversion kinetics. Studies were conducted to determine the acid dissociation constant of TPT's phenolic –OH and interconversion kinetics between TPT's lactone and carboxylate forms. Using the constants determined from these studies and release studies conducted at varying pH, permeability coefficients and membrane binding constants for each species of TPT were determined. Based on this model, three permeable species were observed. Interestingly, the two most permeable species were zwitterionic forms of TPT, and the permeability of the lactone zwitterion was comparable to that of the neutral form of another camptothecin analogue. Furthermore, release was affected by based-catalyzed interconversion kinetics between TPT's lactone and carboxylate forms. At neutral pH, release was rate-limited by formation of the TPT lactone from the ring-opened carboxylate form. Based on these findings, the developed model describing liposomal release of TPT may be used in the future to evaluate and optimize loading and subsequent release of liposomal TPT formulations utilizing active loading strategies.

Investigation of the factors affecting the carbohydrate–lectin interaction by ITC and QCM-D

Although the carbohydrate–lectin interactions have been intensively investigated, there is little report concerning the factors that affect the carbohydrate–lectin interaction. The interactions between concanavalin A (Con A) and glycopolymers, namely poly(2-(methacrylamido)-glucopyranose) and poly(2-methacrylamido-2-deoxy-glucitol) containing pyranose ring form and open form of glucosamine, respectively, have been investigated by a combination of isothermal titration calorimetry and quartz crystal microbalance-dissipation. Our results show that not only the pyranose ring form of glucosamine but also the open form can bind to Con A. Moreover, we investigate the influence of temperature on the carbohydrate–lectin interaction. As the temperature increases, the carbohydrate–lectin interaction is enhanced.

Theoretical Exploration of Photoisomerization-Switchable Second-Order Nonlinear Optical Responses of Two-Dimendional Λ- and W-Shaped Polyoxometalate Derivatives of Dithienylperfluorocyclopentene

The switchable second-order nonlinear optical (NLO) properties on two-dimensional (2D) molecules based on Lindqvist-type [Mo6O19](2-) and dithienylperfluorocyclopentene (DTE) have been investigated at density functional theory (DFT) level. The CAM-B3LYP and M06-2X functionals were employed to study the switching behavior on NLO properties by photoisomerization reaction. The βtot value of system 2c (closed-ring form) is 15920.5 au, which is 150.1 times larger than that of the corresponding open-ring form (system 2o). The time-dependent DFT calculations predict that the charge transfer from DTE to polyoxometalate, and DTE intramolecular charge transfer in closed-ring systems effectively improve the static first hyperpolarizability. Furthermore, the Λ-shaped systems possess a larger u value than those of W-shaped systems owing to different orientation for substituent groups.

Highly Sensitive and Selective Rhodamine-Based “Off–On” Reversible Chemosensor for Tin (Sn4+) and Imaging in Living Cells

A structurally characterized new oxo-chromene functionalized rhodamine derivative L1 exhibits high selectivity toward Sn(4+) by forming a 1:1 complex, among other biologically important metal ions, as studied by fluorescence, absorption, and HRMS spectroscopy. Complexing with Sn(4+) triggers the formation of a highly fluorescent ring-open form which is pink in color. The sensor shows extremely high fluorescence enhancement upon complexation with Sn(4+), and it can be used as a "naked-eye" sensor. DFT computational studies carried out in mimicking the formation of a 1:1 complex between L1 and Sn(4+) resulted in a nearly planar pentacoordinate Sn(IV) complex. Studies reveal that the in situ prepared L1-Sn complex is selectively and fully reversible in presence of sulfide anions. Further, confocal microscopic studies confirmed that the receptor shows in vitro detection of Sn(4+) ions in RAW cells.

Drug Adsorption Property of Surfaces of Polarized Calcium Phosphate Powders

Calcium phosphate powders (hydroxyapatite, α-tricalcium phosphate, β-tricalcium phosphate, and tetracalcium phosphate) were electrically polarized by an applied dc voltage. Thermally stimulated depolarization current measurements confirmed that each calcium phosphate powder exhibited surface charges after polarization treatment. The surface adsorption of simvastatin on each powder was investigated. We observed a difference in adsorption between polarized and non-polarized powders. This difference in adsorption is due to the electrostatic force between the polarized surface and the open-ring form of simvastatin, which has a larger electrical polarity than its closed-ring form.

Visible light photocatalytic activity of aromatic polyamide dendrimer/TiO2 composites functionalized with spirolactam-based molecular switch

A novel aromatic polyamide dendrimer-TiO2 hybrid photocatalyst functionalized with spirolactam-based molecular switch (RG-TiO2) was synthesized. The materials were characterized by FT-IR and scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and UV–vis diffuse reflectance spectroscopy, in comparison with reference materials (plain TiO2). The photocatalytic activity and photostability of RG-TiO2 were investigated based on the degradation of phenol under visible light irradiation. The results showed that the RG-TiO2 hybrid photocatalyst enhanced photocatalytic efficiency of photodegradation of phenol compared with the as-prepared plain TiO2 under visible light irradiation. More significantly, when the RG-TiO2 was acidified to pH 3, the RG-TiO2 was readily transformed from spirolactam form (OFF) to the ring-opened amide form (ON). And the photocatalytic stability of ring-opened RG-TiO2 (switch off form) was much lower than that of ring-closed RG-TiO2 (switch on form). The novel fabrication method of the TiO2 photocatalyst provides a valuable way for developing highly efficient and controllable photocatalysts by molecular switch.

Haloboration of internal alkynes with boronium and borenium cations as a route to tetrasubstituted alkenes.

Hail boration! 2-Dimethylaminopyridine-ligated dihaloborocations [X2B(2-DMAP)](+) with a strained four-membered boracycle were used for the haloboration of terminal and dialkyl internal alkynes (see scheme). Esterification then provided vinyl boronate esters as useful precursors to tetrasubstituted alkenes. Following mechanistic studies, the scope of the haloboration was expanded simply by variation of the amine. Pin = 2,3-dimethyl-2,3-butanedioxy.