Optical Sensing of Aromatic Amino Acids and Dipeptides by a Crown-Ether-Functionalized Perylene Bisimide Fluorophore.

The host-guest binding properties of a fluorescent perylene bisimide (PBI) receptor equipped with crown ether were studied in detail with a series of aromatic amino acids and dipeptides by UV/Vis, fluorescence and NMR spectroscopy. Fluorescence titration experiments showed that electron-rich aromatic amino acids and dipeptides strongly quench the fluorescence of the electron-poor PBI host molecule. Benesi-Hildebrand plots of fluorescence titration data confirmed the formation of host-guest complexes with 1:2 stoichiometry. Binding constants determined by global analysis of UV/Vis and fluorescence titration experiments revealed values between 103 m-1 and 105 m-1 in acetonitrile/methanol (9:1) at 23 °C. These data showed that amino acid l-Trp having an indole group and dipeptides containing this amino acid bind to the PBI receptor more strongly than other amino acids and dipeptides investigated here. For dipeptides containing l-Trp or l-Tyr, the binding strength is dependent on the distance between the ammonium group and the aromatic unit of the amino acids and dipeptides leading to a strong sensitivity for Ala-Trp dipeptide. 1D and 2D NMR experiments also corroborated 1:2 host-guest complexation and indicated formation of two diastereomeric species of host-guest complexes. The studies have shown that a properly functionalized PBI fluorophore functions as a molecular probe for the optical sensing of aromatic amino acids and dipeptides.

Sensing of Double-Stranded DNA/RNA Secondary Structures by Water Soluble Homochiral Perylene Bisimide Dyes.

A broad series of homochiral perylene bisimide (PBI) dyes were synthesized that are appended with amino acids and cationic side chains at the imide positions. Self-assembly behavior of these ionic PBIs has been studied in aqueous media by UV/Vis spectroscopy, revealing formation of excitonically coupled H-type aggregates. The interactions of these ionic PBIs with different ds-DNA and ds-RNA have been explored by thermal denaturation, fluorimetric titration and circular dichroism (CD) experiments. These PBIs strongly stabilized ds-DNA/RNA against thermal denaturation as revealed by high melting temperatures of the formed PBI/polynucleotide complexes. Fluorimetric titrations showed that these PBIs bind to ds-DNA/RNA with high binding constants depending on the number of the positive charges in the side chains. Thus, spermine-containing PBIs with six positive charges each showed higher binding constants (logKs =9.2-9.8) than their dioxa analogues (logKs =6.5-7.9) having two positive charges each. Induced circular dichroism (ICD) of PBI assemblies created within DNA/RNA grooves was observed. These ICD profiles are strongly dependent on the steric demand of the chiral substituents of the amino acid units and the secondary structure of the DNA or RNA. The observed ICD effects can be explained by non-covalent binding of excitonically coupled PBI dimer aggregates into the minor groove of DNA and major groove of RNA which is further supported by molecular modeling studies.

J-aggregates: from serendipitous discovery to supramolecular engineering of functional dye materials.

J-aggregates are of significant interest for organic materials conceived by supramolecular approaches. Their discovery in the 1930s represents one of the most important milestones in dye chemistry as well as the germination of supramolecular chemistry. The intriguing optical properties of J-aggregates (in particular, very narrow red-shifted absorption bands with respect to those of the monomer and their ability to delocalize and migrate excitons) as well as their prospect for applications have motivated scientists to become involved in this field, and numerous contributions have been published. This Review provides an overview on the J-aggregates of a broad variety of dyes (including cyanines, porphyrins, phthalocyanines, and perylene bisimides) created by using supramolecular construction principles, and discusses their optical and photophysical properties as well as their potential applications. Thus, this Review is intended to be of interest to the supramolecular, photochemistry, and materials science communities.

Self-assembled pi-stacks of functional dyes in solution: structural and thermodynamic features.

This critical review provides an overview on the formation of pi-stacks of functional dyes in solution, aiming to acquaint young researchers with this topical research field and to stimulate further advance in supramolecular dye chemistry. Different mathematical models that have been proposed and applied for the description of aggregation equilibria of pi-systems in solution are discussed. The factors that have significant impact on the structural features of aggregates and the thermodynamics of pi-pi stacking such as electrostatic interactions, size and geometry of the dye molecules are covered in this review. A comparison of the binding strength is made for different classes of functional pi-conjugated systems, from simple benzene to more extended polycyclic hydrocarbon molecules, including triphenylenes and hexabenzocoronenes, heteroaromatic porphyrins and phthalocyanines, quadrupolar naphthalene and perylene bisimides, dipolar or even zwitterionic merocyanines and squaraines, and some macrocyclic dyes. Solvent effects on binding constants are analysed by linear free energy relationships with various solvent polarity scales (98 references with multiple entries).

Cytotoxicity and genotoxicity induced by the photochemical alkoxyl radical source N-tert-butoxypyridine-2-thione in L5178Y mouse lymphoma cells under UVA irradiation.

The cell-damaging effects of N-tert-butoxypyridine-2-thione (tBuOPT), which generates alkoxyl and thiyl radicals on photolysis, have been investigated in L5178Y mouse lymphoma cells. The UVA irradiation of 2.5 microM tBuOPT inhibits strongly cell growth and cell viability, causes pronounced membrane damage, and induces micronuclei. Without irradiation, tBuOPT does not cause any cell damage at 2.5 microM concentration. The phototoxicity of tBuOPT is effectively inhibited by the radical scavenger glutathione, while the photogenotoxicity (micronuclei induction) is not affected by this strong hydrogen-atom donor. Thus, for the cytotoxicity and genotoxicity different reactive species seems to be responsible. The cytotoxicity is presumably caused by oxyl radicals, which are derived from tert-butoxyl radicals generated by photocleavage of tBuOPT, while in the genotoxicity the less reactive pyridyl-2-thiyl radicals appear to play a role. These results demonstrate that N-alkoxypyridinethiones are useful photochemical sources of oxyl and thiyl radicals to elucidate biological effects caused by these free radicals.

Opposite enantioselectivities of two phenotypically and genotypically similar strains of Pseudomonas frederiksbergensis in bacterial whole-cell sulfoxidation.

Soil samples were screened to select microorganisms with the capability to oxidize organic sulfides into the corresponding sulfoxides with differential enantioselectivities. Several bacterial strains that preferentially produced the S-configured sulfoxide enantiomer were isolated. Surprisingly, one bacterial strain, genotypically and phenotypically characterized as Pseudomonas frederiksbergensis, selectively gave the R enantiomer. The finding that two apparently identical organisms displayed opposite enantioselectivities is novel for non-genetically modified organisms.

Preparation and characterization of regioisomerically pure 1,7-disubstituted perylene bisimide dyes.

A detailed study on bromination and subsequent imidization of perylene bisanhydride with cyclohexylamine is reported. The present results reveal that previously reported 1,7-difunctionalized perylene bisimides are presumably contaminated with the respective 1,6 regioisomers. N,N'-Dicyclohexyl-1,7-dibromoperylene bisimide 1,7-3 is obtained for the first time in isomerically pure form, and its structure is unequivocally confirmed by X-ray analysis. By using regioisomerically pure 1,7-dibromoperylene bisimide 1,7-3, 1,7-dipyrrolidinylperylene bisimides 4a-c and 1,7-dipyrrolidinylperylene bisanhydride 5 as well as the unsymmetrically difunctionalized 1-bromo-7-pyrrolidinyl- and 1-cyano-7-pyrrolidinylperylene bisimides 7 and 8 are synthesized in good yield.

Synthesis and electropolymerization of novel oligothiophene-functionalized perylene bisimides.

Fourfold oligothiophene-functionalized perylene bisimides have been synthesized by esterification of hydroxyphenoxy-substituted perylene bisimides and their optical properties as well as electrochemical polymerization properties have been investigated.

Reactivity, chemoselectivity, and diastereoselectivity of the oxyfunctionalization of chiral allylic alcohols and derivatives in microemulsions: comparison of the chemical oxidation by the hydrogen peroxide/sodium molybdate system with the photooxygenation.

The chiral allylic alcohols 1a-d and their acetate (1e) and silyl ether (1f) derivatives have been oxidized by the H2O2/MoO4(2)- system, a convenient and efficient chemical source of singlet oxygen. This chemical peroxidation (formation of the allylic hydroperoxides 2) has been conducted in various media, which include aqueous solutions, organic solvents, and microemulsions. The reactivity, chemoselectivity, and diastereoselectivity of this chemical oxidation are compared to those of the sensitized photooxygenation, with the emphasis on preparative applications in microemulsion media. While a similar threo diastereoselectivity is observed for both modes of peroxidation, the chemoselectivity differs significantly, since in the chemical oxidation with the H2O2/MoO4(2)- system the undesirable epoxidation by the intermediary peroxomolybdate competes efficiently with the desirable peroxidation by the in situ generated singlet oxygen. A proper choice of the type of microemulsion and the reaction conditions furnishes a high chemoselectivity (up to 97%) in favor of threo-diastereoselective (up to 92%) peroxidation.

Metallosupramolecular squares: from structure to function.

Metallosupramolecular squares have been successfully evolved over the past years as versatile substitutes of the conventional organic macrocycles owing to the development of reliable synthetic protocols and abundant structural variability (metals and ligands). In this review we have presented the fundamental aspects of metallosupramolecular squares such as the strategies for their construction (self-assembly vs. kinetically controlled macrocyclization) and characterization. The major emphasis of this tutorial review lies on the function of metallosupramolecular squares. Thus, the introduction of functionality into these systems has been discussed in detail by highlighting the recent progress toward application in various fields, including molecular recognition, enantioselective sensing, photoluminescence, redox activity and electrochemical sensing, and homogeneous catalysis.

Chiral hydroperoxides as oxygen source in the catalytic stereoselective epoxidation of allylic alcohols by sandwich-type polyoxometalates: control of enantioselectivity through a metal-coordinated template.

The epoxidation of allylic alcohols is shown to be efficiently and selectively catalyzed by the oxidatively resistant sandwich-type polyoxometalates, POMs, namely [WZnM(2)(ZnW(9)O(34))(2)](q)(-) [M = OV(IV), Mn(II), Ru(III), Fe(III), Pd(II), Pt(II), Zn(II); q = 10-12], with organic hydroperoxides as oxygen source. Conspicuous is the fact that the nature of the transition metal M in the central ring of polyoxometalate affects significantly the reactivity, chemoselectivity, regioselectivity, and stereoselectivity of the allylic alcohol epoxidation. For the first time, it is demonstrated that the oxovanadium(IV)-substituted POM, namely [ZnW(VO)(2)(ZnW(9)O(34))(2)](12-), is a highly chemoselective, regioselective, and also stereoselective catalyst for the clean epoxidation of allylic alcohols. A high enantioselectivity (er values up to 95:5) has been achieved with [ZnW(VO)(2)(ZnW(9)O(34))(2)](12)(-) and the sterically demanding TADOOL-derived hydroperoxide TADOOH as regenerative chiral oxygen source. Thus, a POM-catalyzed asymmetric epoxidation of excellent catalytic efficiency (up to 42 000 TON) has been made available for the development of sustainable oxidation processes. The high reactivity and selectivity of this unprecedented oxygen-transfer process are mechanistically rationalized in terms of a peroxy-type vanadium(V) template.

A highly chemoselective, diastereoselective, and regioselective epoxidation of chiral allylic alcohols with hydrogen peroxide, catalyzed by sandwich-type polyoxometalates: enhancement of reactivity and control of selectivity by the hydroxy group through metal-alcoholate bonding.

Sandwich-type polyoxometalates (POMs), namely [WZnM2(ZnW9O34)2]q- [M = Mn(II), Ru(III), Fe(III), Pd(II), Pt(II), Zn(II); q = 10-12], are shown to catalyze selectively the epoxidation of chiral allylic alcohols with 30% hydrogen peroxide under mild conditions (ca. 20 degrees C) in an aqueous/organic biphasic system. The transition metals M in the central ring of polyoxometalate do not affect the reactivity, chemoselectivity, or stereoselectivity of the allylic alcohol epoxidation by hydrogen peroxide. Similar selectivities, albeit in significantly lower product yields, are observed for the lacunary Keggin POM [PW11O39]7-, in which a peroxotungstate complex has been shown to be the active oxidizing species. All these features support a tungsten peroxo complex rather than a high-valent transition-metal oxo species operates as the key intermediate in the sandwich-type POM-catalyzed epoxidations. On capping of the hydroxy functionality through acetylation or methylation, no reactivity of these hydroxy-protected substrates [1a(Ac) and 1a(Me)] is observed by these POMs. A template is proposed to account for the marked enhancement of reactivity and selectivity, in which the allylic alcohol is ligated through metal-alcoholate bonding, and the H2O2 oxygen source is activated in the form of a peroxotungsten complex. 1,3-Allylic strain promotes a high preference for the threo diastereomer and 1,2-allylic strain a high preference for the erythro diastereomer, whereas tungsten-alcoholate bonding furnishes high regioselectivity for the epoxidation of the allylic double bond. The estimated dihedral angle alpha of 50-70degrees for the metal-alcoholate-bonded template of the POM/H2O2 system provides the best compromise between 1,2A and 1,3A strain during the oxygen transfer. In contrast to acyclic allylic alcohols 1, the M-POM-catalyzed oxidation of the cyclic allylic alcohols 4 by H2O2 gives significant amounts of enone.

Highly efficient catalytic asymmetric epoxidation of allylic alcohols by an oxovanadium-substituted polyoxometalate with a regenerative TADDOL-derived hydroperoxide.

The oxovanadium(IV) sandwich-type POM catalyzes the chemo-, regio-, and stereoselective epoxidation of allylic alcohols by chiral hydroperoxides with very high catalytic efficiency (up to 42 000 TON), a potentially valuable oxidation for the development of sustainable processes. By using the sterically demanding, TADDOL-derived hydroperoxide TADOOH as the chiral oxygen source, enantiomeric ratios (er) of up to 95:5 have been achieved.

Efficient pi-facial control in the ene reaction of nitrosoarene, triazolinedione, and singlet oxygen with tiglic amides of the bornane-derived sultam as chiral auxiliary: an economical synthesis of enantiomerically pure nitrogen- and oxygen-functionalized acrylic acid derivatives.

The ene reaction of 4-nitronitrosobenzene (ArNO), N-phenyl-1,2,4-triazoline-3,5-dione (PTAD), and singlet oxygen (1O2) with the optically active tiglic-acid derivatives of Oppolzer's bornane-derived sultam affords the respective ene products regioselectively in excellent diastereoselectivity (de up to 99%) and in good yield (55-90%). The enophiles ArNO and PTAD give with the methyl-substituted substrate exclusively the like-configured ene adduct, while 1O2 leads to an 83:17 diastereomeric mixture. With the sterically more demanding isopropyl-substituted derivative even the smallest enophile 1O2 forms exclusively the like diastereomer. The high diastereoselectivity is rationalized in terms of the proper conformational alignment of the substrate and a preferred enophilic attack from the C(beta)-re face of the double bond. This concept offers an efficient synthetic route to enantiomerically pure nitrogen- and oxygen-functionalized acrylic acid derivatives.

Studies on cytotoxic and genotoxic effects of N-hydroxypyridine-2-thione (Omadine) in L5178Y mouse lymphoma cells.

The cytotoxicity and genotoxicity of the antifungal and antimicrobial agent Omadine, i.e. N-hydroxypyridine-2-thione (HOPT), has been investigated in L5178Y mouse lymphoma cells in the dark and under UVA irradiation. Omadine inhibits cell growth and induces micronuclei at concentrations >0.5 microM in the absence of light. At a 0.5-microM concentration, an UVA-dose-dependent induction of micronuclei is observed, conditions at which the cytotoxicity and genotoxicity in the dark is negligible. The photogenotoxicity is not accompanied by cytotoxicity. Control experiments with the radical scavengers GSH and GSHOEt implicate the involvement of hydroxyl radicals in the photogenotoxicity of Omadine.

Photochemistry of N-isopropoxy-substituted 2(1H)-pyridone and 4-p-tolylthiazole-2(3H)-thione: alkoxyl-radical release (spin-trapping, EPR, and transient spectroscopy) and its significance in the photooxidative induction of DNA strand breaks.

UVA-irradiation of the photo-Fenton reagents N-isopropoxypyridone 2b and N-isopropoxythiazole-2(3H)-thione 3b releases radicals which induce strand breaks. Transient spectroscopy establishes N-O bond scission [Phi(N)(-)(O) = (75 +/- 8)% for 2b and (65 +/- 7)% 3b] as the dominating primary photochemical process to afford the DNA-damaging radicals. Product studies and laser-flash experiments reveal that the thiazolethione 3b leads primarily to the disulfide 5, from which through C-S bond breakage, the bithiazyl 6, the thiazole 7, and the isothiocyanate 8 are derived. Upon irradiation of pyridone 2b (300 nm) in aqueous media, a mixture of isopropoxyl and 2-hydroxyprop-2-yl radicals is formed, as confirmed by trapping with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and EPR spectroscopy. In contrast, the photolysis of the thiazolethione 3b (350 nm) affords exclusively the DMPO adducts of the isopropoxyl radicals. Control experiments disclose that the thiazolethione-derived photoproduct disulfide 5, or the intermediary thiyl radicals B, scavenge the carbon-centered 2-hydroxyprop-2-yl radicals, which are generated from the isopropoxyl radicals by hydrogen shift. With supercoiled pBR 322 DNA in a 60:40 mixture of H(2)O-MeCN, the pyridone 2b and the thiazolethione 3b display moderate strand-break activity (17% open-circular DNA for 2b and 12% for 3b). In pure water, however, the pyridone 2b photoinduces substantially more DNA cleavage (32% open-circular DNA), which is attributed to the peroxyl radicals generated from the 2-hydroxyprop-2-yl radicals by oxygen trapping. The lower strand-break activity of the thiazolethione 3b derives presumably from isopropoxyl radicals, because only these are detected in the photolysis of this photo-Fenton reagent.

cis-Stilbene and (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)benzene as mechanistic probes in the Mn(III)(salen)-catalyzed epoxidation: influence of the oxygen source and the counterion on the diastereoselectivity of the competitive concerted and radical-type oxygen transfer.

cis-Stilbene (1) has been epoxidized by a set of diverse oxygen donors [OxD], catalyzed by the Mn(III)(salen)X complexes 3 (X = Cl, PF(6)), to afford a mixture of cis- and trans-epoxides 2. The cis/trans ratios range from 29:71 (extensive isomerization) to 92:8, which depends both on the oxygen source [OxD] and on the counterion X of the catalyst. When (1 alpha,2 beta,3 alpha)-(2-ethenyl-3-methoxycyclopropyl)-benzene (4) is used as substrate, a mechanistic probe which differentiates between radical and cationic intermediates, no cationic ring-opening products are found in this epoxidation reaction; thus, isomerized epoxide product arises from intermediary radicals. The dependence of the diastereoselectivity on the oxygen source is rationalized in terms of a bifurcation step in the catalytic cycle, in which concerted Lewis-acid-activated oxygen transfer competes with stepwise epoxidation by the established Mn(V)(oxo) species. The experimental counterion effect is attributed to the computationally assessed ligand-dependent reaction profiles and stereoselectivities of the singlet, triplet, and quintet spin states available to the manganese species.

A comparative photomechanistic study (spin trapping, EPR spectroscopy, transient kinetics, photoproducts) of nucleoside oxidation (dG and 8-oxodG) by triplet-excited acetophenones and by the radicals generated from alpha-oxy-substituted derivatives through Norrish-type I cleavage.

The photooxidation of 2'-deoxyguanosine (dG) and its derivative 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) by a series of acetophenones (AP-X) and benzophenone (BP) has been studied. The favorable absorption characteristics of the benzoyl chromophore enables time-resolved spectroscopy of the triplet ketones to assess their quenching kinetics by dG and 8-oxodG. Whereas the photolysis of acetophenone (AP), 2-acetoxyacetophenone (AP-OAc), and benzophenone (BP) does not produce radicals (group A ketones), the oxymethyl-substituted derivatives 2-hydroxyacetophenone (AP-OH) and 2-tert-butoxyacetophenone (AP-O(t)Bu) lead to carbon-centered radicals by alpha cleavage (group B ketones). For the latter ketones, this was confirmed by EPR studies with the spin trap 5,5-dimethylpyrroline N-oxide (DMPO) and by their triplet lifetimes that were shorter than those for the unsubstituted acetophenone. Both groups of ketones photooxidize dG and 8-oxodG; the oxidation products are spiroiminodihydantoin and guanidine-releasing products (GRP) in the case of dG and AP-OH also 8-oxodG. In the presence of O(2), the photooxidation by the group A ketones is efficient at high dG or 8-oxodG concentrations, whereas the group B ketones photooxidize dG and 8-oxodG also at low substrate concentrations. These results imply that peroxyl radicals are responsible for the photooxidation by the group B ketones, which are formed by alpha cleavage of the triplet ketone and subsequent O(2) trapping of the carbon-centered radicals. At higher dG concentrations, direct electron transfer from dG to the triplet ketone, as observed for the group A ketones, competes with the radical activity.

2'-Deoxyguanosine (DG) oxidation and strand-break formation in DNA by the radicals released in the photolysis of N-tert-butoxy-2-pyridone. Are tert-butoxyl or methyl radicals responsible for the photooxidative damage in aqueous media?

[reaction: see text] The photolysis of pyridone 3b (photo-Fenton reagent) in benzene releases tert-butoxyl radicals, which have been trapped by DMPO and EPR-spectrally identified. In aqueous solution, however, the fragmentation of the tert-butoxyl into methyl radicals prevails and the former radicals are of no direct consequence in the photooxidation of 2'-deoxyguanosine (dG) and pBR 322 DNA. The photooxidative damage of nucleic acids is caused by the oxyl radical species generated from the methyl radicals with oxygen.