Vincent M. Lynch

Highly luminescent poly(methyl methacrylate)-incorporated europium complex supported by a carbazole-based fluorinated β-diketonate ligand and a 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide co-ligand.

A novel efficient antenna complex of Eu(3+) [Eu(CPFHP)(3)(DDXPO)] supported by a highly fluorinated carbazole-substituted β-diketonate ligand, namely, 1-(9H-carbazol-2-yl)-4,4,5,5,5-pentafluoro-3-hydroxypent-2-en-1-one (CPFHP) and the 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene oxide (DDXPO) ancillary ligand, has been synthesized, structurally characterized, and its photoluminescent behavior examined. The single-crystal X-ray diffraction analysis of Eu(CPFHP)(3)(DDXPO) revealed that this complex is mononuclear, and that the central Eu(3+) ion is surrounded by eight oxygen atoms, six of which are provided by the three bidentate β-diketonate ligands. The remaining two oxygen atoms are furnished by the chelating phosphine oxide ligand. The coordination polyhedron is best described as that of a distorted square antiprism. The photophysical properties of Eu(CPFHP)(3)(DDXPO) benefit from adequate protection of the metal by the ligands with respect to non-radiative deactivation as well as an efficient ligand-to-metal energy transfer process which exceeds 66% in chloroform solution with a quantum yield of 47%. As an integral part of this work, the synthesis, characterization, and luminescent properties of poly(methyl methacrylate) (PMMA) polymer films doped with Eu(CPFHP)(3)(DDXPO) are also reported. The luminescent efficiencies of the doped films (photoluminescence quantum yields 79-84%) are dramatically enhanced in comparison with that of the precursor complex. The new luminescent PMMA-doped Eu(CPFHP)(3)(DDXPO) complex therefore shows considerable promise for polymer light-emitting diode and active polymer optical fiber applications.

Synthetic ion transporters can induce apoptosis by facilitating chloride anion transport into cells

Anion transporters based on small molecules have received attention as therapeutic agents because of their potential to disrupt cellular ion homeostasis. However, a direct correlation between a change in cellular chloride anion concentration and cytotoxicity has not been established for synthetic ion carriers. Here we show that two pyridine diamide-strapped calix[4]pyrroles induce coupled chloride anion and sodium cation transport in both liposomal models and cells, and promote cell death by increasing intracellular chloride and sodium ion concentrations. Removing either ion from the extracellular media or blocking natural sodium channels with amiloride prevents this effect. Cell experiments show that the ion transporters induce the sodium chloride influx, which leads to an increased concentration of reactive oxygen species, release of cytochrome c from the mitochondria and apoptosis via caspase activation. However, they do not activate the caspase-independent apoptotic pathway associated with the apoptosis-inducing factor. Ion transporters, therefore, represent an attractive approach for regulating cellular processes that are normally controlled tightly by homeostasis.

A Highly Selective Low-Background Fluorescent Imaging Agent for Nitric Oxide

We introduce a novel sensing mechanism for nitric oxide (NO) detection with a particular easily synthesized embodiment (NO(550)), which displays a rapid and linear response to NO with a red-shifted 1500-fold turn-on signal from a dark background. Excellent selectivity was observed against other reactive oxygen/nitrogen species, pH, and various substances that interfere with existing probes. NO(550) crosses cell membranes but not nuclear membranes and is suitable for both intra- and extracellular NO quantifications. Good cytocompatibility was found during in vitro studies with two different cell lines. The high specificity, dark background, facile synthesis, and low pH dependence make NO(550) a superior probe for NO detection when used as an imaging agent.

Ion-Mediated Electron Transfer in a Supramolecular Donor-Acceptor Ensemble

Charging Back and Forth Ion binding by proteins can exert a major influence on electron transfer events in biological systems. Park et al. (p. 1324) discovered an analogous phenomenon in a simpler synthetic system. Specifically, a certain flexible molecule, known as a calix[4]pyrrole derivative, adopts a conical conformation upon binding anions, such as chloride or bromide, and this in turn leads to electron transfer to a guest acceptor that drifts into the cone. Addition of a cation that fitted more snugly into the conical cavity resulted in a reversal of the electron transfer reaction. The whole process was mapped out by spectroscopic and crystallographic characterization of the intermediates and products. Electron transfers in a weakly bound molecular complex are driven forward by anions and backward by cations. Ion binding often mediates electron transfer in biological systems as a cofactor strategy, either as a promoter or as an inhibitor. However, it has rarely, if ever, been exploited for that purpose in synthetic host-guest assemblies. We report here that strong binding of specific anions (chloride, bromide, and methylsulfate but not tetrafluoroborate or hexafluorophosphate) to a tetrathiafulvalene calix[4]pyrrole (TTF-C4P) donor enforces a host conformation that favors electron transfer to a bisimidazolium quinone (BIQ2+) guest acceptor. In contrast, the addition of a tetraethylammonium cation, which binds more effectively than the BIQ2+ guest in the TTF-C4P cavity, leads to back electron transfer, restoring the initial oxidation states of the donor and acceptor pair. The products of these processes were characterized via spectroscopy and x-ray crystallography.

Crown-6-Calix(4)arene Capped Calix(4)pyrrole: An Ion Pair Receptor for Solvent Separated CsF Ions

An ion-pair receptor, 1, containing both cation- and anion-recognizing sites, has been synthesized and characterized. Single-crystal X-ray diffraction structural studies and (1)H NMR spectroscopic analyses confirmed that 1 forms stable 1:1 complexes with CsF in solution and in the solid state in spite of the large separation enforced between the receptor-bound anion and cation. In 9:1 CDCl3/CD3OD, binding of fluoride anion within the calix[4]pyrrole core of 1 was not observed in the absence of a cobound cesium cation; however, it was seen in this solvent mixture under conditions where a Cs(+) cation was bound to the crown ether-strapped calix[4]arene subunit.

Benzene-, pyrrole-, and furan-containing diametrically strapped calix[4]pyrroles - An experimental and theoretical study of hydrogen-bonding effects in chloride anion recognition

Weak hydrogen bonds recently have arisen as a topic of interest in supramolecular chemistry.[1] Among the various interactions being studied, the C-H···anion hydrogen bonds have drawn considerable attention. Positively-charged groups, such as imidazolium cations, provide strong C-H donors and have been used extensively in the design of numerous anionophore architectures.[2] There is increasing evidence, however, that even charge-neutral C-H donors may be strong enough to be exploited effectively in anion recognition chemistry. Such interactions, which involve both aliphatic and aryl C-H groups, have been inferred from gas phase studies,[3] deduced from NMR spectroscopic studies via, e.g., chemical shifts changes,[4-7] and observed in solid state structures.[4,5,8] A recent review of anion-arene adducts notes that C-H···anion hydrogen bonding, rather than interaction with the π-system, is by far the most prevalent bonding motif observed in the solid state.[9] These experimental observations are supported by theoretical analyses.[10,11] For instance, Hay and co-workers have calculated that benzene C-H···anion hydrogen bonds are significant,[11a] being roughly half the strength of typical neutral N-H···anion hydrogen bonds. In a subsequent theoretical report, it was noted that the aryl C-H···Cl binding energies in the gas phase can be tuned from –8 to –16 kcal/mol by altering the para substitution from NH2 to NO2.[11b] Although there are a couple examples where complementary aryl C-H anion interactions have been deliberately incorporated into the design of anion receptors,[7,12] to the best of our knowledge, no efforts have been made to date to test theoretical predictions via the synthesis and experimental study of a matched series of anion receptors. We now report efforts along these lines.

Using Enantioselective Indicator Displacement Assays To Determine the Enantiomeric Excess of α-Amino Acids

Enantioselective indicator displacement assays (eIDAs) were used for the determination of enantiomeric excess (ee) of alpha-amino acids as an alternative to the labor-intensive technique of chromatography. In this study, eIDAs were implemented by the use of two chiral receptors [(Cu(II)(1)](2+), [Cu(II)(2)](2+)) in conjunction with the indicator chrome azurol S. The two receptors were able to enantioselectively discriminate 13 of the 17 analyzed alpha-amino acids. Enantiomeric excess calibration curves were made using both receptors and then used to analyze true test samples to check the systems ability to determine ee accurately. The proposed method uses a conventional UV-vis spectrophotometer to monitor the colorimetric signal, which allows for a potential high-throughput screening (HTS) method for determining ee. The techniques created consistently produced results accurate enough for rapid preliminary determination of ee.

Diaminocarbene[3]ferrocenophanes and their transition-metal complexes.

N-heterocyclic carbenes (NHCs) form robust complexes with nearly every transition metal. In many instances, these complexes function as catalysts with superior activities and selectivities. The broad utility and application of NHCs can be traced to synthetic advancements which enable access to derivatives with novel N substituents and architectures. We envisioned that it would be possible to create a new class of carbene-based ligands with relatively wide N-C-N angles and redox-switchable functions by linking diaminocarbenes to 1,1’-disubstituted metallocenes. In view of the affinity of carbenes for transition metals, the use of such ligands may lead to new redox-active complexes with tunable electronic properties. Herein, we describe a novel carbene architecture that contains a 1,1’-disubstituted ferrocene moiety and demonstrate its ability to engage in unique electronic interactions with coordinated transition metals. The formamidinium salts 1a and 1b were synthesized in up to 95 % yield by the formylative cyclization of the respective 1,1’-dianilinoor 1,1’-dialkylaminoferrocene precursor upon treatment with trimethylorthoformate and HBF4. [8] Diagnostic formamidinium signals were found at d = 9.3 and 8.8 ppm ([D6]DMSO), respectively, in the H NMR spectra of these compounds. The solid-state structure of 1a reveals eclipsed cyclopentadienyl (Cp) ligands, which are tilted toward each other (f = 15.78) as a result of the tethering effect of the diaminocarbene fragment (Figure 1, left). This strain is manifested in a relatively large N-C-N angle of 129.6(3)8, a value that is comparable to those

Positive Homotropic Allosteric Receptors for Neutral Guests: Annulated Tetrathiafulvalene-Calix[4]pyrroles as Colorimetric Chemosensors for Nitroaromatic Explosives

The study of positive homotropic allosterism in supramolecular receptors is important for elucidating design strategies that can lead to increased sensitivity in various molecular recognition applications. In this work, the cooperative relationship between tetrathiafulvalene (TTF)-calix[4]pyrroles and several nitroaromatic guests is examined. The design and synthesis of new annulated TTF-calix[4]pyrrole receptors with the goal of rigidifying the system to accommodate better nitroaromatic guests is outlined. These new derivatives, which display significant improvement in terms of binding constants, also display a positive homotropic allosteric relationship, as borne out from the sigmoidal nature of the binding isotherms and analysis by using the Hill equation, Adair equation, and Scatchard plots. The host-guest complexes themselves have been characterized by single-crystal X-ray diffraction analyses and studied by means of UV-spectroscopic titrations. Investigations into the electronic nature of the receptors were made by using cyclic voltammetry; this revealed that the binding efficiency was not strictly related to the redox potential of the receptor. On the other hand, this work serves to illustrate how cooperative effects may be used to enhance the recognition ability of TTF-calix[4]pyrrole receptors. It has led to new allosteric systems that function as rudimentary colorimetric chemosensors for common nitroaromatic-based explosives, and which are effective even in the presence of potentially interfering anions.

Ion-Controlled On–Off Switch of Electron Transfer from Tetrathiafulvalene Calix[4]pyrroles to Li+@C60

Binding of chloride anion to a tetrathiafulvalene calix[4]pyrrole (TTF-C4P) donor results in ET to Li(+)@C(60) to produce the radical pair (TTF-C4P(•+)/Li(+)@C(60)(•-)), the structure of which was characterized by X-ray crystallographic analysis. The addition of tetraethylammonium cation, which binds more effectively than Li(+)@C(60)(•-) as a guest within the TTF-C4P cavity, leads to electron back-transfer, restoring the initial oxidation states of the donor and acceptor pair.