Syndiotactic-specific polymerization of NIPAAm

The radical polymerization of N-isopropylacrylamide (NIPAAm) was carried out in toluene at low temperatures in the presence of silyl alcohols, such as triethylsilanol (TESiOH). Poly(NIPAAm) with a racemo dyad content of 75 % was obtained at –80 °C with a 4:1 TESiOH to monomer ratio loading. NMR analysis has suggested that the mechanism for syndiotactic induction, in the presence of silyl alcohols, may be similar to that observed with alkyl alcohols. In this case, a 1:2 complex formation, via hydrogen bonding interactions, leads to the induction of syndiotactic specificity

Hydrogen-bond-assisted syndiotactic-specific radical polymerization of N-isopropylacrylamide : The solvent effect on the stereospecificity

Radical polymerizations of N-isopropylacrylamide (NIPAAm) in several solvents at low temperatures in the absence or presence of hexamethylphosphoramide (HMPA) or 3-methyl-3-pentanol (3Me3PenOH) were examined. The isotacticities of the poly(NIPAAm)s obtained in the absence of HMPA and 3Me3PenOH at lower temperatures slightly increased as the polarities of the solvents used increased. The addition of HMPA significantly induced the syndiotactic-specificity even in polar solvents such as tetrahydrofuran and acetone, although the use of the solvents having proton-donating ability, such as chloroform, prevented the induction of the syndiotactic-specificity, even if their polarities are low. In the presence of 3Me3PenOH, a good correlation between the polarities of the solvents used and the syndiotacticities of the obtained poly(NIPAAm)s was observed, and poly(NIPAAm) with r = 73% was obtained using the toluene/methylcyclohexane mixed solvent

Heterotactic poly(N-isopropylacrylamide) prepared via radical polymerization in the presence of fluorinated alcohols

Radical polymerization of N-isopropylacrylamide in toluene at –40°C in the presence of fourfold amounts of fluorinated alcohols was investigated. The 13C NMR analysis of the obtained polymers suggested that the addition of fluorinated alcohols induced heterotactic-specificity in radical polymerization of NIPAAm, although syndiotactic poly(NIPAAm)s were obtained by adding alkyl alcohols as we have previously reported. To the best of our knowledge, this is the first synthesis of heterotactic poly(NIPAAm)

RADICAL POLYMERIZATIONS OF N-ALKYLACRYLAMIDES

The radical polymerizations of N-alkylacrylamides, such as N-methyl- (NMAAm), N-n-propyl- (NNPAAm), N-benzyl- (NBnAAm), and N-(1-phenylethyl)acrylamides (NPhEAAm), at low temperatures were investigated in the absence or presence of hexamethylphosphoramide (HMPA) and 3-methyl-3-pentanol (3Me3PenOH), which induced the syndiotactic-specificities in the radical polymerization of N-isopropylacrylamide (NIPAAm). In the absence of the syndiotactic-specificity inducers, the syndiotacticities of the obtained polymers gradually increased as the bulkiness of the N-substituents increased. Both HMPA and 3Me3PenOH induced the syndiotactic-specificities in the NNPAAm polymerizations as well as in the NIPAAm polymerizations. The addition of 3Me3PenOH into the polymerizations of NMAAm significantly induced the syndiotactic-specificities, whereas the tacticities of the obtained polymers were hardly affected by adding HMPA. In the polymerizations of bulkier monomers, such as NBnAAm and NPhEAAm, HMPA worked as the syndiotactic-specificity inducer at higher temperatures, whereas 3Me3PenOH hardly influenced the stereospecificity, regardless of the temperatures. The phase transition behaviors of the aqueous solutions of poly(NNPAAm)s were also investigated. It appeared that the poly(NNPAAm) with racemo dyad content of 70% exhibited unusual large hysteresis between the heating and cooling processes

HETEROTACTIC POLY(N-ISOPROPYLACRYLAMIDE)

Radical polymerization of N-isopropylacrylamide (NIPAAm) in toluene at low temperatures, in the presence of fluorinated alcohols, produced heterotactic polymer comprising an alternating sequence of meso and racemo dyads. The heterotacticity reached 70% in triads when polymerization was carried out at –40°C using nonafluoro-tert-butanol as the added alcohol. NMR analysis revealed that formation of a 1:1 complex of NIPAAm and fluorinated alcohol through C=O•••H-O hydrogen bonding induces the heterotactic specificity. A mechanism for the heterotactic-specific polymerization is proposed. Examination of the phase transition behavior of aqueous solutions of heterotactic poly(NIPAAm) revealed that the hysteresis of the phase transition between the heating and cooling cycles depended on the average length of meso dyads in poly(NIPAAm)

RUNX inhibitor suppresses graft‐versus‐host disease through targeting RUNX‐NFATC2 axis

Patients with refractory graft-versus-host disease (GVHD) have a dismal prognosis. Therefore, novel therapeutic targets are still needed to be identified. Runt-related transcriptional factor (RUNX) family transcription factors are essential transcription factors that mediate the essential roles in effector T cells. However, whether RUNX targeting can suppress, and GVHD is yet unknown. Here, we showed that RUNX family members have a redundant role in directly transactivating NFATC2 expression in T cells. We also found that our novel RUNX inhibitor, Chb-M’, which is the inhibitor that switches off the entire RUNX family by alkylating agent–conjugated pyrrole-imidazole (PI) polyamides, inhibited T-cell receptor mediated T cell proliferation and allogenic T cell response. These were designed to specifically bind to consensus RUNX-binding sequences (TGTGGT). Chb-M’ also suppressed the expression of NFATC2 and pro-inflammatory cytokine genes in vitro. Using xenogeneic GVHD model, mice injected by Chb-M’ showed almost no sign of GVHD. Especially, the CD4 T cell was decreased and GVHD-associated cytokines including tissue necrosis factor-α and granulocyte-macrophage colony-stimulating factor were reduced in the peripheral blood of Chb-M’ injected mice. Taken together, our data demonstrates that RUNX family transcriptionally upregulates NFATC2 in T cells, and RUNX-NFATC2 axis can be a novel therapeutic target against GVHD