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Solution phase synthetic method for amyloid-cleaving catalysts was developed, which bears triazine core, scaffold with bulky and that have various solubility properties; Co(III) complex of cyclen (1,4,7,10-tetraazacyclododecane) for catalytic group, and two imaging agents for binding group. This synthetic method was identified by H-NMR, C-NMR for intermediates and MS for the last products. The yields by this method surpassed solid phase synthesis and took much lower labor, expense, and time. The products which were synthesized by solution phase synthetic method showed good catalytic activities.

Lithium stannides were prepared from lithium naphthalenide and tin (II) chloride or tin (0) powder in THF solvent at room temperature under dry argon atmosphere. They were characterized with elemental analysis, XRD, and solid 6,7Li NMR. Stabilities and reactivities of lithium stannides prepared from different conditions were tested and showed they were stable for a limited time at low temperatures. Best reactivity was obtained when they were prepared from tin (II) chloride and an excess of lithium naphthalenide. The lithium stannide mixture can reductively cleave carbon–halogen bonds and yield pinacol coupling with aldehydes. Organolithium compounds prepared from lithium stannides and organic halides add to ketones or aldehydes under Barbier conditions.

Type 2 diabetes mellitus (T2DM) is a fatal disorder disease that is characterized by substantial β-cell mass reduction in the context of insulin deficiency. Previous researches have demonstrated that human islet amyloid polypeptide (h-IAPP), an oligopeptide monomer with 37 amino acid residues, induces apoptotic cell-death in β-cells and causes a development of T2DM. Previous studies have also shown that fibrils, which are the final form of aggregated h-IAPP, are not necessarily the most toxic form of amyloid protein in general. Oligomers may induce βcell apoptosis. Therefore, tremendous efforts have been conducted to develop drugs which prevent h-IAPP from forming oligomers. For instance, the use of oligomerspecific antibodies has been investigated, as well as the use of Cu(II) ion, which prevents h-IAPP from forming the βsheet conformers, and cleavage agents with Co(III) cyclen and Cu(II) cyclen. Cleavage agent with Cu(II) cyclen has been proposed as novel catalytic drug. Candidates for catalytic drug are mainly composed of two parts. One part is the catalytic group that hydrolyzes the peptide bond of h-IAPP. This part is composed of Cu(II) cyclen complex, which allows for secreted Cu(II) ions to act as oligomer inhibitors. The other part is the binding group that binds to h-IAPP through hydrophobic interactions. In regards to the hydrolysis reaction by Cu(II) cyclen complex, reaction time is critical and closely connected with the binding group’s capacity since the cleavage agent cleaves only the oligomer form and has limited reaction time. Therefore, it is necessary to synthesize the catalytic drug candidate with the other binding group. Proposed binding group is I-Box-derived one. Benzothiazoleanilines (BTAs) functional group has higher affinity for the hydrophobic amyloid than I-Box(2-(4'-dimethylaminophenyl)-6-iodobenzoxazole) and BTAs also have a ability to cross the blood-brain barrier (BBB) well. Figure 1 shows the proposed structure of Cu(II) cyclen cleavage agent with BTA-derived binding group (Fig. 1). New Cu(II) cleavage agent with BTA-derived binding group was synthesized and the efficiency of this noble agent for h-IAPP cleavage was tested. Figure 2 shows that the MALDI-TOF TOF MS spectrum of fragmentation pattern when h-IAPP was incubated with new Cu(II) cleavage agent with BTA-derived binding group. According to the previous literatures, residues 20-29 and 30-37 of h-IAPP (37mer) are considered as amyloidogenic region. Peaks shown in Figure 2 indicate the fragments of h-IAPP. This spectrum demonstrates that highly amyloidogenic regions of h-IAPP can exist as dissolved form in solution. This indicates that self aggregation of h-IAPP can be inhibited by this noble agent. In our previous study, we

Familial British Dementia (FBD) is the early-onset autosomal dominant disorders characterized by cognitive impairment. The ABri is a 34-mer peptide which is the main component of amyloid deposits in FBD. As a first step toward shedding light for the discovery of amyloid inhibition drugs for FBD, we set the optimal conditions for quantification ABri peptide by the fluorescamine and alpha imager assay, which can provide a precise peptide quantity for determination of amyloid inhibition rate at micromolecular level and estimate aggregation rate by measuring monomer and dimer quantity which are filtered through 10,000 Da MW cutoff filter.

Type 2 diabetes mellitus (T2DM) is characterized by a substantial reduction in beta-cell mass and the amyloid fibrils which are formed by the aggregation of the human islet amyloid polypeptide (h-IAPP) in the islet of Langerhans. Cleavage agents with Co(III) cyclen as the catalytic group have been studied as a novel therapeutic option for T2DM patients. However, recent research has suggested that the cytotoxicity of h-IAPP might be mediated by interactions with Cu(II); furthermore, it has been shown in vitro that Cu(II) prevents h-IAPP from forming the beta-sheet conformers. Therefore, we synthesized a cleavage agent using Cu(II) cyclen. The resulting cleaved fragments and estimated cleavage yield (8.3mol%) were evaluated after incubation with h-IAPP.

Lead, strontium and barium nitrates, like the titanates of the same cations, form a continuous set of solid solutions. 207Pb NMR spectra of mixed crystals of lead/strontium nitrate and lead/barium nitrate each show up to 13 lines, arising from lead ions with from zero to twelve Pb2+ nearest-neighbor cations replaced by Sr2+ or Ba2+. In the case of (Pb,Sr)(NO3)2 these shifted lines are further split by the multiplicity of inequivalent nearest-neighbor replacements. The average shift per Sr2+ ion is 21.8 ppm; that for Ba2+ is smaller. Using Monte Carlo/Metropolis calculations, the intensities of the resonances can be fit to statistical models of Pb2+ and Sr2+ ion distributions, and used to probe the microenergetics of solid solution formation. The data can be satisfactorily fit by distributions in which the cations are slightly clustered, with like pairs of nearest neighbors being favored by 120 J/mol over unlike pairs. Interestingly, this finding is inconsistent with the conventional interpretation of powder diffraction results for the mixed crystals, where the dependence of lattice parameter on composition shows a slight positive curvature, generally held to indicate a favorable interaction between unlike ions.

207Pb NMR spectra of mixed crystals of anhydrous lead and strontium nitrate show up to 13 lines, arising from lead ions with 0-12 Pb(2+) nearest-neighbor cations replaced by Sr(2+). The shifted lines are further split by the multiplicity of inequivalent nearest-neighbor replacements. The average shift per Sr(2+) ion is 21.8 ppm. Similar but somewhat smaller effects are seen in [Pb,Ba](NO(3))(2) mixed crystals. The intensities of the resonances can be fit to Monte Carlo models of Pb(2+) and Sr(2+) ion distributions and are consistent with like nearest-neighbor pairs being 120 J/mol lower in energy than unlike pairs.