João C. Lima

Convenient Synthesis of 3-Vinyl and 3-Styryl Coumarins

A variety of 2-hydroxy aldehydes on reaction with 3-butenoic acid afford in a one-pot reaction the corresponding 3-vinylcoumarins. As expected, extension of the delocalized π-electron system accomplished by Heck coupling reactions with aryl halides results in an increased fluorescence of the compounds whose applicability is yet to be established.

The effect of self-aggregation on the determination of the kinetic and thermodynamic constants of the network of chemical reactions in 3-glucoside anthocyanins.

The six most common 3-glucoside anthocyanins, pelargonidin-3-glucoside, peonidin-3-glucoside, delphinidin-3-glucoside, malvidin-3-glucoside, cyanidin-3-glucoside and petunidin-3-glucoside were studied in great detail by NMR, UV-vis absorption and stopped flow. For each anthocyanin, the thermodynamic and kinetic constants of the network of chemical reactions were calculated at different anthocyanin concentration, from 6 × 10⁻⁶ M up to 8 × 10⁻⁴ M; an increasing of the flavylium cation acidity constant to give quinoidal base and a decreasing of the flavylium cation hydration constant to give hemiketal were observed by increasing the anthocyanin concentration. These effects are attributed to the self-aggregation of the flavylium cation and quinoidal base, which is stronger in the last case. The UV-vis and ¹H NMR spectral variations resulting from the increasing of the anthocyanin concentration were discussed in terms of two aggregation models; monomer-dimer and isodesmic, the last one considering the formation of higher order aggregates possessing the same aggregation constant of the dimer. The self-aggregation constant of flavylium cation at pH=1.0, calculated by both models increases by increasing the number of methoxy (-OCH₃) or hydroxy (-OH) substituents following the order: myrtillin (2 -OH), oenin (2 -OCH₃), 3-OGl-petunidin (1 -OH, 1 -OCH₃), kuromanin (1 -OH), 3-OGl-peonidin (1 -OCH₃) and callistephin (none). Evidence for flavylium aggregates possessing a shape between J and H was achieved, as well as for the formation of higher order aggregates.

Elucidation of the multiple equilibria of malvin in aqueous solution by One- and two-dimensional NMR

Abstract One- and two-dimensional NMR were used to characterize the several forms of malvin present in aqueous solution in the pH range 0.3–4.5 and to determine their molar fractions as a function of pH. In addition to the flavylium cation, two hemiacetal forms and both the cis and trans forms of chalcone were firmly identified. The pathways for the interconversion of the different forms were derived and the molar absorbances of the species calculated by coupling NMR and UV/Vis data. Equilibrium constants were determined at different temperatures, and enthalpy and entropy changes were calculated for the interconversion processes. The conclusions are supported by molecular orbital calculations.

Phosphine-gold(I) compounds as anticancer agents: general description and mechanisms of action.

Gold complexes have been explored as metallodrugs with great potential applications as antitumoral agents. In particular, gold-phosphine derivatives seemed quite promising since the use of the antiarthritic auranofin drug (thiolate-Au-PEt3 complex) presented also biological activity against different cancer cells. So, different auranofin analogues have been explored within this context and for this reason, the main number of phosphine-gold complexes developed with this goal contain thiolate ligands. Other complexes have been also studied such as tetrahedral bis(phosphine)gold(I) and phosphine-gold-halides. Very recently, phosphine-gold-alkynyl complexes have also shown very interesting biological activities although few reports are published related to them. Their mechanism of action seems to be clearly different that the used by platinum drugs (DNA intercalating processes) and recent studies point to be related to the inhibition of Trx reductase. Cellular uptake and biodistribution studies are well reported in the original works but the use of luminescence techniques is relatively less explored. For this, the use of these techniques is also specifically reported in this review.

Anion detection by fluorescent Zn(II) complexes of functionalized polyamine ligands.

The Zn(2+) coordination chemistry and luminescent behavior of two ligands constituted by an open 1,4,7-triazaheptane chain functionalized at both ends with 2-picolyl units and either a methylnaphthyl (L1) or a dansyl (L2) fluorescent unit attached to the central amino nitrogen are reported. The fluorescent properties of the ZnL1(2+) and ZnL2(2+) complexes are then exploited toward detection of anions. L1 in the pH range of study has four protonation constants. The fluorescence emission from the naphthalene fluorophore is quenched either at low or at high pH values leading to an emissive pH window centered around pH = 5. In contrast, in L2 the fluorescence emission from the dansyl unit occurs only at basic pH values. In the case of L1, a red-shifted band appearing in the visible region was assigned to an exciplex emission involving the naphthalene and the tertiary amine of the polyamine chain. L1 forms Zn(2+) mononuclear complexes of ZnH(p)L1((p+2)+) stoichiometry with p = 1, 0, -1. Formation of the ZnL1(2+)species produces a strong enhancement of the L1 luminescence leading to an extended emissive pH window from pH = 5 to pH = 9. Addition of several anions to this last complex leads to a partial quenching effect. On the contrary, the fluorescence emission of L2 is partially quenched upon complexation with Zn(2+) in the same pH window (5 < pH < 9). The lower stability of ZnL2(2+) with respect to ZnL1(2+) suggests a lack of involvement of the sulfonamide group in the first coordination sphere. However, there is spectral evidence for an interesting photoinduced binding of the sulfonamide nitrogen to Zn(2+). While addition of diphosphate, triphosphate, citrate, and D,L-isocitrate to a solution of ZnL2(2+) restores the fluorescence emission of the system (lambda max ca. 600 nm), addition of phosphate, chloride, iodide, and cyanurate do not produce any significant change in fluorescence. Moreover, this system would permit one to differentiate diphosphate and triphosphate over citrate and d, l-isocitrate because the fluorescence enhancement observed upon addition of the first anions is much sharper. The ZnL2(2+) complex and its mixed complexes with diphosphate, triphosphate, citrate, and D,L-isocitrate have been characterized by (1)H, (31)P NMR, and Electrospray Mass Spectrometry.

Water/humidity and ammonia sensor, based on a polymer hydrogel matrix containing a fluorescent flavylium compound

Flavylium compounds can conveniently be encapsulated in water permeable cross-linked poly(2-hydroxyethyl methacrylate) (PHEMA) polymer hydrogel matrices. The polymer is also permeable to gases, for example ammonia and hydrogen chloride. The ability of the polymer to concentrate water from the surrounding atmosphere was demonstrated. The absorption and emission spectra of the encapsulated flavylium compounds are very dependent on the pH, and by consequence ammonia (or hydrogen chloride) can be easily detected. The intensity of the fluorescence emission of the flavylium cation (AH+ species obtained in acidic media) is very dependent on the water content due to the efficient excited state proton transfer involving the AH+* excited state and water. The combination of flavylium emission sensitivity to water and ability of the polymer to concentrate water from the surrounding atmosphere, confers this material potential utility as a humidity sensor with high sensitivity.

Kinetics of ultra-fast excited state proton transfer from 7-hydroxy-4-methylflavylium chloride to water

Abstract Excited state proton transfer from 7-hydroxy-4-methylflavylium chloride to water is reported. From a modified analysis of picosecond time-resolved fluorescence data (not using the lifetime of a parent compound), all rate constants were determined: the deprotonation rate constant of the flavylium cation, k d =1.4×10 11 s −1 , the protonation rate constant of the base form, k p =2.3×10 10 l mol −1 s −1 and the reciprocal fluorescence lifetimes of these species, k AH + =7.8×10 9 s −1 ( τ AH + =128 ps) and k A =7.6×10 9 s −1 ( τ A =132 ps), in water, at 20°C. The value of k d is the largest measured value for an intermolecular proton transfer (to water).

Switching from intramolecular energy transfer to intramolecular electron transfer by the action of pH and Zn2+ co-ordination

Abstract Intramolecular electron (eT) and energy transfer (ET) have shown to occur in a covalently linked donor–acceptor (CLDA) system consisting of a naphthalene donor covalently linked through a polyamine chain connector to an anthracene acceptor; the connector has been chosen in order to switch ON or OFF the energy flux as a function of its protonation state as well as by co-ordination to Zn 2+ . The largest energy transfer efficiency ( η =0.61) occurs for the fully protonated form (pH 9 (eT) from the lone pairs of the nitrogens to the excited fluorophore takes place, leading to complete quenching of the emission. On the other hand at neutral and basic pH values, co-ordination of Zn 2+ prevents the eT quenching allowing the ET process to occur.

Neutral Gold(I) Metallosupramolecular Compounds: Synthesis and Characterization, Photophysical Properties, and Density Functional Theory Studies

The reaction of the tris-indole InTREN ligand (L) with different gold phosphine fragments allows the construction of new gold(I) complexes with different geometries depending on the chosen phosphine. A metallodendrimeric structure is obtained when the gold atom is linked to a triphenylphosphine ligand, and neutral gold(I) metallocryptands are constructed when a triphosphine is used. Characterization of the compounds was accomplished by 31P{1H} and 1H NMR, IR, absorption, and fluorescence spectroscopies, electrospray ionization mass spectrometry (ESI-MS(+)), and elemental analysis, and their geometry was optimized using density functional theory (B3LYP). Time-dependent density functional theory (TD-DFT) calculations have been used to assign the lowest energy absorption bands to LMCT N(p, tertiary amine)-->Au transitions. Photophysical characterization of the complexes shows strong luminescence in the solid state. The formation of heterobimetallic species has been detected in solution in the presence of equimolar quantities of metal cations, and their structures have been identified by a combination of spectroscopic methods and mass spectrometry.

Nanophotonics for Molecular Diagnostics and Therapy Applications

Light has always fascinated mankind and since the beginning of recorded history it has been both a subject of research and a tool for investigation of other phenomena. Today, with the advent of nanotechnology, the use of light has reached its own dimension where light-matter interactions take place at wavelength and subwavelength scales and where the physical/chemical nature of nanostructures controls the interactions. This is the field of nanophotonics which allows for the exploration and manipulation of light in and around nanostructures, single molecules, and molecular complexes. What is more is the use of nanophotonics in biomolecular interactions—nanobiophotonics—has prompt for a plethora of molecular diagnostics and therapeutics making use of the remarkable nanoscale properties. In this paper, we shall focus on the uses of nanobiophotonics for molecular diagnostics involving specific sequence characterization of nucleic acids and for gene delivery systems of relevance for therapy strategies. The use of nanobiophotonics for the combined diagnostics/therapeutics (theranostics) will also be addressed, with particular focus on those systems enabling the development of safer, more efficient, and specific platforms. Finally, the translation of nanophotonics for theranostics into the clinical setting will be discussed.