Photoinduced electron transfer fluorometric Hg(II) chemosensor based on a BODIPY armed with a tetrapod receptor.

From the great variety of BODIPY based-chemosensors able to determine Hg(2+), only a small portion has been applied to its determination in environmental and/or biological samples. The lack of studies on the analytical performance of the latter sensors makes interesting the development of investigations oriented to their possible analytical applications. The synthesis of a BODIPY derivative armed with a tetrapod receptor is described. The procedure is based on a previous publication, and the modifications performed to improve the synthesis include alternative procedures with different objectives, as the consecution of a multigram synthesis, improving the low yields of some of the previously proposed procedure steps, simplifying the experimental steps, achieving the desired purity requirements for use with analytical purposes, and enriching the characterization of the implied structures. The characteristics of its selectivity towards Hg(2+) have been investigated, and the OFF-ON fluorometric response, based on a photo-electron transfer (PET) mechanism, served as the base for the development of a method able to determine Hg(2+) in environmental waters at ng mL(-1) levels. The intrinsic fluorescence of the BODIPY core is inhibited and the probe exhibits a weak fluorescence (i.e. "OFF" state due to the deactivating PET effect). Upon complexation, Hg(2+) interacts with the lone-pair electrons on the nitrogen atoms of the receptor moiety so that the electronic transfer from the receptor to the photo-excited fluorophore is slowed down or switched off (i.e. "ON" state due to the suppression of the deactivating PET effect by coordination of the analyte to the probe). Regarding the complex photostability in aqueous solution, it is mandatory to conduct the experiments at darkness due to its photodegradation. The stoichiometry studies indicated a 1:2 relationship for the BODIPY-Hg(2+) complex. The high selectivity towards mercuric ions is considerably influenced by pH, being necessary to conduct the experiments in a pH value higher than 6. Calibration samples were prepared by adding appropriate amounts of Hg(2+) between 20.0-120.0 ng mL(-1), at a constant BODIPY concentration of 1 µmol L(-1). After agitating for 5 min at darkness, phosphate buffer (pH=7.50) was added, and it was diluted to the mark with water. Fluorescence measurements were carried out at 18 °C, exciting at 515 nm, and obtaining fluorescence emission at 538 nm. The method has been satisfactory applied to Hg(2+) determination in environmental water samples.

Can we predict the conformational preference of amides?

To what extent, if any, is the conformation of secondary amides revealed by theory? This question has now been addressed by computational methods using calculations at the B3LYP/6-31G level of theory and (1)H NMR spectroscopy. Both gas-phase and solvent studies predict a Z-anti conformation to be the lowest in energy for an evaluated series of acetamides. Moreover, Z-anti conformations may also be inferred from the chemical shifts of the N-CH alpha protons determined by NMR spectroscopy. Thus, a proton situated anti to the N-H proton consistently appears approximately 0.8 ppm further downfield than a proton situated gauche to the N-H proton. This finding, which could only be derived by using the DFT calculations of conformational preference as a guide to interpret the NMR data, might prove to be useful as a simple and convenient methodology for establishing amide conformation experimentally.

Three- and four-membered rings from cycloadditions of 1,3-thiazolium-4-olates and aldehydes.

2-Aminothioisomünchnones, a well-known family of masked dipoles, react with aromatic aldehydes in a domino cascade reaction that produces episulfides (thiiranes) or beta-lactams (2-azetidinones). This sequence is initiated by a [3+2] dipolar cycloaddition followed by ring opening of cycloadducts and intramolecular rearrangement to afford these unusual ring contractions. The nature of the reaction products depends on the structural characteristics of the starting dipole and the experimental conditions. Episulfides are obtained selectively as cis isomers with respect to both aryl groups, whereas beta-lactams are produced as cis/trans mixtures. These structural features were determined unequivocally by X-ray crystallographic analysis. The beta-lactams still possessed a flexible acyclic chain containing sulfur, a salient lead modification of the bioactive cyclic penems and cephems. The preferential production of exo transition structures was rationalized with the aid of computational calculations at the B3LYP/6-31G* level.

Synergic effect of vicinal stereocenters in [3 + 2] cycloadditions of carbohydrate azadipolarophiles and mesoionic dipoles: origin of diastereofacial selectivity.

The intermolecular [3 + 2] cycloaddition of carbohydrate-derived 1,2-diaza-1,3-butadienes and 1,3-thiazolium-4-olates provides a conceptual basis for the problem of diastereofacial preference in the acyclic series of unsaturated sugars. Experimental results employing a side chain of D-arabino configuration have shown the stereodifferentiation exerted by the first stereogenic center that renders the Re,Re face of the acyclic sugar-chain azadiene eligible for cycloaddition (J. Org. Chem. 2000, 65, 5089). The results of the present work, now utilizing an alternative framework of D-lyxo configuration, evidence the discriminating power of the second stereogenic carbon, which induces the preferential approach to the Re,Si face of the heterocyclic dipole. This scheme of face selectivity is also grounded in theoretical calculations at a semiempirical level. In addition to dihydrothiophenes, which are the expected products of the [3 + 2] cycloaddition, bicyclic systems based on dihydrothieno[2,3-c]piperidine skeleton can also be obtained.

The first density functional study on the

The hetero-Diels-Alder reactions of 1,2-diaza-1,3-butadiene with ethylene, methyl vinyl ether, and methyl acrylate have been investigated theoretically with the aid of density functional theory using the Becke3LYP/6-31G(d) computational level. In the reactions with substituted alkenes, the transition states are concerted but asynchronous; the shortest bond-forming distance involves the nonsubstituted carbon of the alkene. In agreement with the experimental results, the reaction with methyl vinyl ether proceeds with high endo stereoselectivity and with complete regioselectivity to form the 6-methoxy cycloadduct. The conformational study of the transition states shows a sharp s-trans preference. In contrast, the [4 + 2]-cycloaddition of 1,2-diaza-1,3-butadiene with methyl acrylate have been found to occur with low regio- and stereoselectivity but with a s-cis preference in the transition structures.

Computational studies on the BF3-catalyzed cycloaddition of furan with methyl vinyl ketone: a new look at Lewis acid catalysis

Transition structures for both uncatalyzed and BF3-catalyzed Diels-Alder reactions involving furan and methyl vinyl ketone have been determined at the hybrid DFT (B3LYP/6-31G*) level of theory. The transition structures are predicted to be relatively concerted and highly asynchronous in all cases. A subsequent bond-order analysis has been carried out at the MP2/6-31G*//B3LYP/6-31G*. The role of the Lewis acid and the origin of the endo selectivity have been discussed in terms of the nature and number of interactions present in the four possible transition structures. The partition of the potential energy barrier has also been used to estimate the contributions of the pure deformation energy and the differential interaction between the reaction partners on passing from the ground state to the saddle point. This analysis reveals that the major influence arises from the heterodiene-dienophile interaction instead of that corresponding to a BF3-dienophile interaction.

Diastereoselective cycloadditions of 1,3-thiazolium-4-olates with chiral 1,2-diaza-1,3-butadienes

A series of 2-(N-methyl)benzylamino-1,3-thiazolium-4-olates (2-aminothioisomunchnones) react with chiral 1,2-diaza-1,3-butadienes derived from carbohydrates to afford a diastereomeric mixture of (4R,5S)- and (4R,5R)-4,5-dihydrothiophenes. These substrate-controlled cycloadditions are chemoselective, regiospecific, and proceed with a high facial diastereoselection. A theoretical rationale at semiempirical level does justify the stereochemical outcome observed in the experiments.

Reactions of 2-amino-2-thiazolines with isocyanates and isothiocyanates. Chemical and computational studies on the regioselectivity, adduct rearrangement, and mechanistic pathways.

2-Amino-2-thiazoline derivatives bearing alkyl or aryl substituents at exocyclic nitrogen have been condensed with different isocyanates and isothiocyanates. The addition occurs at ring endocyclic nitrogen in a regiospecific manner to afford kinetic and enthalpy-favored adducts. The unequivocal assignment of these structures has been confirmed by X-ray diffraction analyses of several compounds. The endo adducts do not rearrange on heating with the sole exception of adducts in which the exocyclic nitrogen remains unsubstituted. Trapping experiments in the presence of other isocyanates or isothiocyanates produce the formation of new endo adducts by acyl exchange in the reaction mixture. Semiempirical PM3 calculations full corroborate the higher stability of endo or exo adducts depending on the substitution pattern. The formation of adducts is compatible with a stepwise reaction mechanism, for which semiempirical transition structures could be located in the potential energy surface, and the global energetics of the process have been determined. The formation of the endo adducts proceeds with a smaller activation barrier.

Understanding diastereofacial selection in carbohydrate-based domino cycloadditions: semiempirical and DFT calculations.

The sequential cycloaddition of nitroalkenes with methyl vinyl ether was investigated by semiempirical (PM3) and density functional methods (B3LYP/6-31G*). The asymmetric version was also examined with a threoconfigured carbohydrate auxiliary. This produces a larger, more flexible system that complicates the calculation. Most transition structures were then fully optimized at the PM3 level and further refinement was done at ab initio levels. This study represents a model case that enables the rationalization of the high facial selectivity observed in carbohydrate-based nitrone- and nitronate-alkene cycloadditions. The selective endo orientation of the [4+2] pathway results from Coulombic attraction and secondary orbital interactions in the transition state. The stereochemical outcome is largely influenced by a combination of steric shielding from the bulky chiral substituent at C4 and the anomeric effect that places the nitronate C6-alkoxy group in a pseudoaxial arrangement. The resulting conformation favors the subsequent exo approach of methyl vinyl ether to the less hindered re face of the nitronate. It is also remarkable to note that solvation energies stabilize significantly a particular transition structure, thereby explaining the marked stereoselection observed in a polar medium.