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A photo-cross-linkable carboxybetaine (CB)-terminated thiol with only one CB headgroup was introduced to modify gold nanoparticles (GNPs) via self-assembled monolayers (SAMs). This CB-terminated thiol consists of three moieties: (a) an anchoring thiol group, which binds directly to the GNP surface, (b) a CB terminal group, which is highly resistant to protein adsorption, and (c) a diacetylene group in the middle, which is converted to a poly(enyne) structure during UV irradiation via 1,4-topochemical polymerization. Results show that, after cross-linking, CB-modified GNPs are highly resistant to protein adsorption from undiluted human blood serum and cell uptake, and are stable at low pH and high temperature. This cross-linkable CB thiol holds tremendous potentials for biomedical applications where stable and thin coatings are needed.

A simple InBr 3 -catalyzed domino reaction of indoles, phenylacetylenes, and various 3-methyleneoxindolines in toluene is described. This reaction not only provided a convenient synthetic protocol for polysubstituted tetrahydrospiro[carbazole-1,3′-indolines] in good yields but also gave completely different diastereoisomers of the tetrahydrospiro[carbazole-1,3′-indolines] to that of the previously reported TfOH-catalyzed one-pot reaction of indoles, acetophenones, and 3-methyleneoxindolines. Additionally, the InBr 3 -catalyzed reaction of the initially prepared 1,1′bis(indolyl)phenylethanes with 3-phenacylideneoxindolines also gave the corresponding tetrahydrospiro[carbazole-1,3′-indolines] in good yields and with excellent diastereoselectivity. The reaction mechanism involved the sequential in situ generation of reactive dienophilic 3-alkenylindole, the Diels−Alder reaction, and the Lewis acid controlled diastereoisomerization process.

The thromboxane (Tx) A2 pathway is a major contributor to the amplification of initial platelet activation and is therefore a key drug target. To identify potent small-molecule inhibitors of the thromboxane prostaglandin (TP) receptor, we screened a small steroidal saponin library using U46619-induced rat platelet aggregation assays. Timosaponin AIII (TAIII) was identified as a potent inhibitor of U46619-induced rat platelet aggregation and exhibited superior selectivity for the TP receptor versus other G protein-coupled receptors and a PKC activator. TAIII inhibited U46619-induced rat platelet aggregation independent of increases in cAMP and cGMP and the inhibition of TxA2 production. Both PKC and PLC activators restored TAIII-inhibited platelet aggregation, whereas TAIII did not inhibit platelet aggregation induced by co-activation of the G12/13 and Gz pathways. Furthermore, TAIII did not affect the platelet shape change or ROCK2 phosphorylation evoked by low-dose U46619. In vivo, TAIII prolonged tail bleeding time, reduced the mortality of animals with acute pulmonary thromboembolism and significantly reduced venous thrombus weight. Our study suggests that TAIII, by preferentially targeting Gq-mediated PLC/PKC signaling from the TP receptor, induces stronger in vitro antiplatelet activity and in vivo antithrombotic effects and may be an excellent candidate for the treatment of thrombotic disorders.