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The significant variation in photoluminescence emission of poly(diphenylacetylene) derivatives according to the substitution position is due to the differences in the intramolecular pi-stack structure and chain conformation.

Here we report an efficient synthesis of optically active ladder-type molecules and polymers through intramolecular cyclization of chiral triptycenes containing bis[2-(4-alkoxyphenyl)ethynyl]phenylene units. The electrophile-induced cyclization reactions are directed away from the bridgehead carbon atoms of triptycene by steric factors, thereby producing one-handed twisted ladder units without any detectable byproducts. Moreover, the quantitative and regioselective nature of this intramolecular cyclization allowed us to synthesize optically active ladder polymers with a well-defined one-handed helical geometry in which homoconjugated dibenzo[a,h]anthracene units are helically arranged along the main chain. This synthesis route enables the construction of a variety of nanoscale helical ladder architectures and provides an entry into new chiroptical materials., Air Force Office of Scientific Research (Grant 17RT0904)

Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively killing tumour cells harbouring KRAS mutations have remained unavailable. Here we demonstrate the direct targeting of KRAS mutant DNA using a synthetic alkylating agent (pyrrole-imidazole polyamide indole-seco-CBI conjugate; KR12) that selectively recognizes oncogenic codon 12 KRAS mutations. KR12 alkylates adenine N3 at the target sequence, causing strand cleavage and growth suppression in human colon cancer cells with G12D or G12V mutations, thus inducing senescence and apoptosis. In xenograft models, KR12 infusions induce significant tumour growth suppression, with low host toxicity in KRAS-mutated but not wild-type tumours. This newly developed approach may be applicable to the targeting of other mutant driver oncogenes in human tumours.

We investigated sequence-specific DNA alkylation using conjugates between the N-methylpyrrole (Py)-N-methylimidazole (Im) polyamide and the DNA alkylating agent, chlorambucil, or 1-(chloromethyl)-5-hydroxy-1, 2-dihydro-3H-benz[e]indole (seco-CBI). Polyamide-chlorambucil conjugates 1-4 differed in the position at which the DNA alkylating chlorambucil moiety was bound to the Py-Im polyamide. High-resolution denaturing polyacrylamide gel electrophoresis (PAGE) revealed that chlorambucil conjugates 1-4 alkylated DNA at the sequences recognized by the Py-Im polyamide core moiety. Reactivity and sequence specificity were greatly affected by the conjugation position, which reflects the geometry of the alkylating agent in the DNA minor groove. Polyamide-seco-CBI conjugate 5 was synthesized to compare the efficacy of chlorambucil with that of seco-CBI as an alkylating moiety for Py-Im polyamides. Denaturing PAGE analysis revealed that DNA alkylation activity of polyamide-seco-CBI conjugate 5 was similar to that of polyamide-chlorambucil conjugates 1 and 2. In contrast, the cytotoxicity of conjugate 5 was superior to that of conjugates 1-4. These results suggest that the seco-CBI conjugate was distinctly active in cells compared to the chlorambucil conjugates. These results may contribute to the development of more specific and active DNA alkylating agents.

application/pdf, The significant variation in photoluminescence emission of poly(diphenylacetylene) derivatives according to the substitution position is due to the differences in the intramolecular pi-stack structure and chain conformation.

We have designed and synthesized new types of pyrrole (P)-imidazole (I) polyamide conjugates 1 and 2 possessing a suberoylanilide hydroxamic acid (SAHA) moiety that is a strong inhibitor of histone deacetylase (HDAC). SAHA conjugate 2 was designed to target the promoter region of the p16 tumor suppressor gene. The DNA binding affinity of SAHA conjugate 2 to its target sequence was examined using surface plasmon resonance. HDAC inhibition activity of conjugates 1 and 2 was evaluated using a colorimetric assay. The results demonstrated that even though it possesses the relatively large SAHA moiety, conjugate 2 has high DNA sequence-specific binding properties and moderate HDAC inhibitory activity in vitro. SAHA conjugate 2 was found to cause morphological changes in HeLa cells and to induce selective Histone H3 lysine 9 acetylation.

The photonic function of the light-emission from a rigid-rod conjugated polymer, poly(9,10-anthracenediyl-ethynylene-1,4-phenylene-ethynylene) [poly(AEPE)], was measured using total internal reflection fluorescence microscopy (TIRFM), which is a single molecule detection technique that is carried out in methanol at room temperature. The light-emission from a single polymer molecule as it slowly and dynamically changes over a cycle lasting a few seconds has been successfully detected using TIRFM with a built-in spectroscope. Special mention must be made of the fact that we were able to observe for the first time fluctuations in the wavelength of the emission spectra resulting from structural changes in a single polymer molecule. Although poly(AEPE) had a rigid-rod main chain, these changes occurred very slowly over a time-scale of several seconds at room temperature. Thus, single molecule spectroscopy appears to be a powerful tool for studying the dynamic behavior of single macromolecules.

A phenylacetylene monomer, 4-(decyloxycarbonyl)phenylacetylene (DecCPA), was synthesized and polymerized by using the combined catalyst system, i.e., [Rh(norbornadiene)Cl]_2 and triethylamine, to give a yellow solid π-conjugated polymer [poly(DecCPA)] having the high molecular weight and the cis-transoidal stereo-regular main chain. Poly(DecCPA) was measured using total internal reflection fluorescence microscopy, which is a single molecule detection technique that is carried out in tetrahydrofuran solution at room temperature, and the light-twinkling of a single molecule was observed. This twinkling is the dynamic photon emission phenomenon of single poly(DecCPA) molecule that we mention specifically as resultant from the time scale-changing very slowly in the time scale of milliseconds and seconds-with changed fluorescent intensity associated with single polymer molecule conformational changing caused by the micro-Brownian motion. Although a molecular dynamics was at the picosecond time scale generally, this poly(DecCPA) molecule had the mode of the molecular motion of π-conjugated main chain did this very slowly in a second time scale was shown.

Two optically active poly(menthoxycarbonylphenyleneethynylene)s were synthesized by polycondensation using a palladium-copper catalyst system. All polymers showed Cotton effects in the absorption region of the main chain, meaning that chirality is induced to the main chain. Moreover, these chiral polymers showed the enantioselective recognition ability for chiral menthol in CD spectra., identifier:https://dspace.jaist.ac.jp/dspace/handle/10119/4947