Synthesis and binding studies of peptide mimetics, anion receptors, and kinase inhibitors

A series of novel purine-based fluoroaryl triazoles were synthesized and assayed for their neuroprotective effects of hippocampal slice culture exposed to amyloid beta (Aß) oligomers. A monofluorinated triazole has been identified which has comparable neuroprotective effect as that of flavopiridol and roscovitine against the Aß induced neurotoxicity. Carnosine and histidine are biologically interesting antioxidants. In order to probe whether they exert their antioxidant effect through metal ion chelation, the Cu(ll) ion chelating abilities of these compounds were measured by UV-vis spectroscopy. Amyloid beta, the major component of senile plaques in Alzheimer\u27s disease, is known to complex transition metal ions through histidine residues. In this study, using ¹H NMR titration experiments, it was shown that histidine binds strongly to Zn(II), Cu(Il), and Fe(III) ions at a biologically relevant pH (pH 7.4), with a stoichiometry of Zn(II): histidine binding of 1:2. Fluorinated boroxines, tris(2,6-difluorophenyl)boroxin (DF), tris(2,4,6- trifluorophenyl)boroxin (TF), and tris(pentafluorophenyl)boroxin (PF) were synthesized and investigated for their fluoride anion binding affinity using multinuclear Nuclear magnetic resonance (NMR) and tandem mass spectroscopic techniques. DFT calculations show that the fluoride ion complex of DF prefers unsymmetrical, covalently bound structure over the symmetrically bridged species by 12.5 kcal/mol --Abstract, page iii

Purine-Based Triazoles

A pharmaceutical composition for inhibiting at least protein kinase in a cell of a subject includes a purine based triazole

,3-Sigmatropic fluorine migration to boron in McLafferty type of rearrangements: Observation of tetrafluorobenzyne radical cation and trifluorobenzyne cation by CID-mass spectrometry

a b s t r a c t The electron-impact mass spectra of the tris(pentafluorophenyl)boroxine (1) and triphenylboroxine (2) were analyzed to probe the McLafferty type of rearrangements involving 1,3-fluorine or 1,3-hydrogen migrations to boron from the adjacent aromatic rings. 1,3-Sigmatropic fluorine migration leading to the McLafferty rearrangement of 1 results in the formation of the tetrafluorobenzyne radical cation (1c), whereas the similar rearrangement involving 1,3-hydrogen rearrangement is not observed for the nonfluorinated analog 2. The DFT calculations show that the activation barrier for the 1,3-fluorine migration in 1 is significantly lower than that for the 1,3-hydrogen migration in 2 (DDG z w33 kcal/ mol), which is in accordance with the observed 1,3-fluorine migration for the fluorinated boroxine and the lack of such rearrangement for the nonfluorinated boroxine. The 1:1 stoichiometry of the fluoride anion with 1 has also been demonstrated by high resolution electrospray ionization time-of-flight mass spectrometry

Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells

Fluoride ion batteries are potential “next-generation” electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion–conducting electrolytes are known only in the solid state. We report a liquid fluoride ion–conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper–lanthanum trifluoride (Cu@LaF_3) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion–mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology

Transition Metal Ion Binding Studies of Carnosine and Histidine: Biologically Relevant Antioxidants

Carnosine and histidine are biologically interesting antioxidants. In order to probe whether they exert their antioxidant effect through metal ion chelation, the Cu(II) ion chelating abilities of these compounds were measured by UV-vis spectroscopy. Both of these compounds showed 1:1 complexations with Cu(II) ions as shown by their Job\u27s plot. The binding constants for histidine and carnosine, as determined by Benesi-Hildebrand method, at pH 7.84 ± 0.18, were found to be 71 and 1.1 M-1, respectively. The unexpectedly lower binding constant values of carnosine show the relatively minor role of the transition metal ion chelation in their antioxidant abilities

NMR Studies of Zinc, Copper, and Iron Binding to Histidine, the Principal Metal Ion Complexing Site of Amyloid-ß Peptide

Amyloid-ß (Aß), the major component of senile plaques in Alzheimer\u27s disease, is known to complex transition metal ions mainly through histidine residues. In this study, using 1H NMR titration experiments, we show that histidine binds strongly to Zn(II), Cu(II), and Fe(III) ions at a biologically relevant pH (pH 7.4), with a stoichiometry of Zn(II): histidine binding of 1:2. The observed deshielding of the chemical shifts and relative line broadening indicate that Fenton-active Cu(II) and Fe(III) bind to histidine relatively more efficiently as compared to Zn(II). Parallel studies showed that glutamic acid and aspartic acid are relatively inefficient in metal ion binding. From these studies, we suggest that Aß-chelated Zn(II) is readily displaced by Cu(II) and Fe(III) ions and leads to a propagation of oxidative stress

Polynorbornene-polyethylene glycol based polymers as electrolyte materials for rechargeable lithium batteries

Polymer electrolytes are a promising alternate to flammable liq. polymer electrolytes. Their use in lithium based rechargeable batteries is limited by low ion cond. (< 10-5 S/cm) and mech. stability. There has been considerable effort to develop dry solid polymer electrolyte materials with higher conductivities (10-4 S/cm) at room temps. Achieving both high cond. and mech. stability in a polymer is challenging. Towards that goal we have synthesized polynorbornene-polyethylene glycol based copolymers. Cond. and mech. properties of these materials were explored towards their use in lithum rechargeable batteries

The Role of Polyphenolic Antioxidants in Health, Disease, and Aging

Polyphenolic antioxidants from dietary sources are frequently a topic of interest due to widespread scientific agreement that they may help lower the incidence of certain cancers, cardiovascular and neurodegenerative diseases, and DNA damage and even may have antiaging properties. On the other hand, questions still remain as to whether some antioxidants could be potentially harmful to health, because an increase in glycation-mediated protein damage (carbonyl stress) has been reported in some cases. Nevertheless, the quest for healthy aging has led to the extensive use of phytochemically derived antioxidants to disrupt age-associated deterioration in physiological function and to prevent many age-related diseases. Although a diet rich in the polyphenolic forms of antioxidants does seem to offer hope in delaying the onset of age-related disorders, it is still too early to define their exact clinical benefit for treating age-related disease. This review critically examines polyphenolic antioxidants, such as flavonoids, curcumene, and resveratrol in health, disease, and aging with the hope that a better understanding of the many mechanisms involved with these diverse compounds may lead to better health and novel treatment approaches for age-related diseases

Fluorinated Boroxin-Based Anion Receptors for Lithium Ion Batteries: Fluoride Anion Binding, Ab Initio Calculations, and Ionic Conductivity Studies

Novel fluorinated boroxines, tris(2,6-difluorophenyl)boroxin (DF), tris(2,4,6-trifluorophenyl)boroxin (TF), and tris(pentafluorophenyl)boroxin (PF), have been investigated for potential applications in lithium ion batteries through fluoride anion binding, ab initio calculations, and ionic conductivity measurements. Structures of the fluorinated boroxines and boroxin-fluoride complexes have been confirmed by comparing their 19F and 11B NMR chemical shifts with those obtained by the DFT-GIAO method. The stoichiometry of the fluoride anion binding to these boroxines has been shown to be 1:1 using 19F NMR and UV-vis spectroscopy. UV-vis spectroscopic studies show the coexistence of more than one complex, in addition to the 1:1 complex, for perfluorinated boroxin, PF. DFT calculations (B3LYP/6-311G**) show that the fluoride ion complex of DF prefers unsymmetrical, covalently bound structure (7) over the symmetrically bridged species (10) by 12.5 kcal/mol. Rapid equilibration of the fluoride anion among the three borons in these boroxines results in a single 19F NMR absorption for all of the aromatic ortho-or para-fluorines at ambient temperature. The effect of these anion receptors on lithium ion conductivities was also explored for potential applications in dual ion intercalating lithium batteries