Fluorescence lifetime of Nile Red as a probe for the hydrogen bonding strength with its microenvironment

The fluorescence lifetime of Nile Red (NR) is not sensitive to dielectric solvent–solute interactions but markedly decreases with the increase of the hydrogen bond donating ability in alcohols because vibrations associated with hydrogen bonding are involved in the deactivation process. The negligible viscosity effect indicates that twisting of the diethylamino moiety of NR does not play significant role in the dissipation of the excitation energy.     

Formation and stability of N-heterocyclic carbenes in water: the carbon acid pKa of imidazolium cations in aqueous solution

We report second-order rate constants kDO (M-1 s-1) for exchange for deuterium of the C(2)-proton of a series of simple imidazolium cations to give the corresponding singlet imidazol-2-yl carbenes in D2O at 25 degrees C and I = 1.0 (KCl). Evidence is presented that the reverse protonation of imidazol-2-yl carbenes by solvent water is limited by solvent reorganization and occurs with a rate constant of kHOH = kreorg = 10(11) s-1. The data were used to calculate reliable carbon acid pK(a)s for ionization of imidazolium cations at C(2) to give the corresponding singlet imidazol-2-yl carbenes in water: pKa = 23.8 for the imidazolium cation, pKa = 23.0 for the 1,3-dimethylimidazolium cation, pKa = 21.6 for the 1,3-dimethylbenzimidazolium cation, and pKa = 21.2 for the 1,3-bis-((S)-1-phenylethyl)benzimidazolium cation. The data also provide the thermodynamic driving force for a 1,2-hydrogen shift at a singlet carbene: K12 = 5 x 10(16) for rearrangement of the parent imidazol-2-yl carbene to give neutral imidazole in water at 298 K, which corresponds to a favorable Gibbs free energy change of 23 kcal/mol. We present a simple rationale for the observed substituent effects on the thermodynamic stability of N-heterocyclic carbenes relative to a variety of neutral and cationic derivatives that emphasizes the importance of the choice of reference reaction when assessing the stability of N-heterocyclic carbenes.     

Cinchona based squaramide catalysed enantioselective Michael addition of α-nitrophosphonates to aryl acrylates: enantioselective synthesis of quaternary α-aminophosphonates

Several cinchona based squaramide catalysts were applied to the asymmetric Michael addition of α-nitroethylphosphonates to acrylic acid aryl esters, resulting in high yields and enantioselectivities. The absolute configuration of one of the quaternary α-nitrophosphonate adducts was deduced from its experimental and calculated CD spectra. The adducts were reduced to their cyclic aminophosphonates by catalytic hydrogenation.     

Redox interactions between structurally different alkylresorcinols and iron(III) in aqueous media: frozen-solution 57Fe Mössbauer spectroscopic studies,redox kinetics and quantum chemical evaluation of the alkylresorcinol reactivities

Iron(III)-containing aqueous solutions of 5-methylresorcinol (5-MR), 5-n-propylresorcinol (5-n-PR) and 4-n-hexylresorcinol (4-n-HR) at pH ~ 3 were studied by means of ⁵⁷Fe transmission Mössbauer spectroscopy. Kinetic considerations were applied to the redox reactions. Density Functional Theory (DFT) calculations were performed for the alkylresorcinol (AR) molecules and their non-alkylated analogue (resorcinol). Mössbauer spectra consisted of quadrupole doublets assigned to high-spin Fe(III) and Fe(II) species. From changes in their relative spectral areas, a gradual reduction of Fe(III) by all the ARs studied was observed. However, significant differences were found for the reduction rates among the ARs. The following series of the reduction rates was established by means of Mössbauer spectroscopy: 4-n-HR ? 5-MR > 5-n-PR, supplemented by rate constants calculated using a kinetic model. DFT calculations resulted in the following series: 4-n-HR ? 5-n-PR > 5-MR ? resorcinol (the latter is not oxidised under the conditions applied). The reversed order of the experimentally observed 5-MR and 5-n-PR oxidation rates may be explained in terms of their different kinetic parameters related to their structure.     

Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability

All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10⁻⁶–10⁻⁵ M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.     

Efficient syntheses of zoledronic acid as an active ingredient of a drug against osteoporosis

The reaction of 1H-imidazol-1-ylacetic acid and two equivalents of phosphorus trichloride/phosphorous acid at 75?°C in sulfolane, or in the presence of catalytic amounts of [bmim][BF₄] afforded zoledronic acid in yields up to 75%. The joint use of the ionic liquid additive and sulfolane as the solvent was synergetic affording highly valuable zoledronic acid in a record yield of 93%.     

Competitive [4 + 2] cycloadditions in equimolar mixtures of 1‐arylphosphole oxides

Four different [4 + 2] cycloadditions were observed to take place in the equimolar mixtures of two different arylphosphole oxides 2a + 2b or 2b + 2c . In addition to the phosphole oxide dimers 3a‐a and 3b‐b , or 3b‐b and 3c‐c , the crossed cycloadducts 3a‐b and 3b‐a , or 3b‐c and 3c‐b were also formed in considerable portions. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:633–635, 2001     

Energy Dissipation Processes of singlet‐excited 1‐Hydroxyfluorenone and its Hydrogen‐bonded Complex with N‐methylimidazole¶

Effects of solvent, pH and hydrogen bonding with N‐methylimidazole (MIm) on the photophysical properties of 1‐hydroxyfluorenone (1HOF) have been studied. Fluorescence lifetime, fluorescence quantum yield and triplet yield measurements demonstrated that intersystem crossing was the dominant process in apolar media and its rate constant significantly diminished with increasing solvent polarity. The acceleration of internal conversion in alcohols paralleled the strength of intermolecular hydrogen bonding. The faster energy dissipation from the singlet‐excited state in cyclohexane was attributed to intramolecular hydrogen bonding. The pK_a of 1HOF decreased from 10.06 to 5.0 on light absorption, and H₃O⁺ quenched the singletexcited molecules in a practically diffusion‐controlled reaction. On addition of MIm in toluene, dual fluorescence was observed, which was attributed to reversible formation of excited hydrogen‐bonded ion pair. Rate constants for the various deactivation pathways were derived from the combined analysis of the steady‐state and the time‐resolved fluorescence results.     

Interaction of 2-hydroxy-substituted Nile red fluorescent probe with organic nitrogen compounds

The fluorescent properties of 2-hydroxy Nile red dye (HONR) proved to be highly sensitive to the basicity of hydrogen bond acceptors. Fluorescence quantum yields and fluorescence decay profiles were measured as the function of the concentration of organic nitrogen compounds in solvents of various polarities. The detailed mechanism and the kinetics of the fluorescence quenching were revealed with the combined analysis of the steady-state and time-resolved spectroscopic data. The relative contribution of the competing reaction steps was found to be very sensitive to the basicity of the additive and to solvent polarity. The most profound change appeared in the unimolecular deactivation pathways of the excited hydrogen-bonded HONR, whereas the formation rate of this species varied to a lesser extent. The dissociation into excited HONR and ground-state base was able to compete with the energy dissipation only when 2,4,6-trimethylpyridine was used as hydrogen bond acceptor in toluene. The bimolecular quenching of the excited hydrogen-bonded complex played significant role in apolar solvents. Proton displacement along the hydrogen bond in the excited complex led to excited ion pairs in polar media.