Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) ⋅ 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) ⋅ 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

Synthesis and Degradation of Vinyl Polymers with Evenly Distributed Thioacetal Bonds in Main Chains: Cationic DT Copolymerization of Vinyl Ethers and Cyclic Thioacetals.

We report a novel method to synthesize degradable poly(vinyl ether)s with cleavable thioacetal bonds periodically arranged in the main chains using controlled cationic copolymerization of vinyl ethers with a 7-membered cyclic thioacetal (7-CTA) via degenerative chain transfer (DT) to the internal thioacetal bonds. The thioacetal bonds, which are introduced into the main chain by cationic ring-opening copolymerization of 7-CTA with vinyl ethers, serve as in-chain dormant species to allow homogeneous propagation of vinyl ethers for all internal segments to afford copolymers with controlled overall and segmental molecular weights. The obtained polymers can be degraded into low- and controlled-molecular-weight polymers with narrow molecular weight distributions via hydrolysis. Various vinyl ethers with hydrophobic, hydrophilic, and functional pendants are available. Finally, one-pot synthesis of multiblock copolymers and their degradation into diblock copolymers are also achieved.

Evaluation of a non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold as a SARS 3CL protease inhibitor.

A non-prime site substituent and warheads combined with a decahydroisoquinolin scaffold was evaluated as a novel inhibitor for severe acute respiratory syndrome (SARS) chymotrypsin-like protease (3CLpro). The decahydroisoquinolin scaffold has been demonstrated to be an effective hydrophobic center to interact with S2 site of SARS 3CLpro, but the lack of interactions at S3 to S4 site is thought to be a major reason for the moderate inhibitory activity. In this study, the effects of an additional non-prime site substituent on the scaffold as well as effects of several warheads are evaluated. For the introduction of a desired non-prime site substituent, amino functionality was introduced on the decahydroisoquinolin scaffold, and the scaffold was constructed by Pd(II) catalyzed diastereoselective ring formation. The synthesized decahydroisoquinolin inhibitors showed about 2.4 times potent inhibitory activities for SARS 3CLpro when combined with a non-prime site substituent. The present results indicated not only the expected additional interactions with the SARS 3CLpro but also the possibility of new inhibitors containing a fused-ring system as a hydrophobic scaffold and a new warhead such as thioacetal.

Miklós Bodanszky Award Lecture: Selective chalcogen chemistry to study protein science.

In recent decades, chemical protein synthesis and the development of chemoselective reactions-including ligation reactions-have led to significant breakthroughs in protein science. Among them are a better understanding of protein structure-function relationships, the study of protein posttranslational modifications, exploration of protein design, unnatural amino acid incorporation, and the study of therapeutic proteins and protein folding. Chalcogen chemistry, especially that of sulfur and selenium, is quite rich, and we have witnessed continuous progress in this field in recent years. In this short review, we will instead summarize three stories that we have recently presented on chalcogen chemistry and its impact on protein science, which was presented in the Miklós Bodanszky Award Lecture at the 35th European Peptide Society Meeting in Dublin, Ireland, 26 August 2018.

Triphenylamine-Based Polythioacetal for Selective Sensing of Mercury(II) with High Specificity and Sensitivity.

Utilizing the mercury (Hg2+)-triggered deprotection of thioacetals to aldehyde groups, we constructed a water-soluble triphenylamine (TPA)-based polythioacetal PTA-TPA with thioacetal groups in the backbones for efficient sensing of Hg2+ in aqueous solutions. PTA-TPA is conveniently prepared by polycondensation of 3, 6-dioxa-1,8-octanedithiol (DODT) with 4-(N,N-diphenylamino) benzaldehyde (TPA-CHO) using thiol-terminated mPEG2k-SH as a capping agent. The interaction of Hg2+ with PTA-TPA activates the aggregation-induced emission (AIE) process of TPA-CHO molecules, which makes the emission enhanced, and the emission color changes to sky blue, while other metal ions do not interfere with the sensing process. PTA-TPA can be used as a highly selective and ultrafast detection system for Hg2+ with a low detection limit (LOD) of 9.88 nM and a fast response of less than 1 min. In addition, the prepared test strips report the presence of Hg2+ with an LOD as low as 1 × 10-5 M. Intracellular imaging applications have demonstrated that PTA-TPA acts as a biocompatible fluorescent probe for efficient Hg2+ sensing in HeLa cells. Overall, the PTA-TPA fluorescence probes have the characteristics of easy synthesis, cost-effective, ultrafast detection speed, high selectivity, and high sensitivity, which can be used in practical applications.

Practical synthesis of peptide C-terminal aldehyde on a solid support.

We have investigated practical synthetic routes for the preparation of peptide aldehyde on a solid support. Peptide aldehyde was synthesized via efficient transformation of acetal/thioacetal structures.

Re2O7-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles.

Re(VII) oxides catalyze the acetalization, monoperoxyacetalization, monothioacetalization and allylation of hemiacetals. The reactions, which take place under mild conditions and at low catalyst loadings, can be conducted using hemiacetals, the corresponding O-silyl ethers, and, in some cases, the acetal dimers. Aldehydes react under similar conditions to furnish good yields of dithioacetals. Reactions of hemiacetals with nitrogen nucleophiles are unsuccessful. 1,2-Dioxolan-3-ols (peroxyhemiacetals) undergo Re(VII)-promoted etherification but not allylation. Hydroperoxyacetals (1-alkoxyhydroperoxides) undergo selective exchange of the alkoxide group in the presence of either Re2O7 or a Brønsted acid.

Crystal structures of 9-[bis-(benzyl-sulfan-yl)meth-yl]anthracene and of cyclo-dodeca-kis-(µ2-phenyl-methane-thiol-ato-κ2 S:S)hexa-palladium(6 Pd-Pd)-anthracene-9,10-dione (1/1).

The first title compound, C29H24S2, L1, represents an example of an anthracene-based functionalized di-thio-ether, which may be useful as a potential chelating or terminal ligand for coordination chemistry. This di-thio-acetal L1 crystallizes in the monoclinic space group P21/c. The phenyl rings of the benzyl groups and that of the anthracene unit form dihedral angles of 49.21 (4) and 58.79 (5)° and the crystal structure displays short C-H⋯π contacts. Surprisingly, when attempting to coordinate L1 to [PdCl2(PhCN)2], instead of the targeted chelate complex [PdCl2(κ2-L1)], a cleavage reaction leads to the formation of the centrosymmetric hexa-nuclear cyclic cluster of composition [Pd6(µ2-SCH2Ph)12] Pd6, or [Pd6(C7H7S)12]·C14H8O2. This tiara-shaped hexa-mer crystallizing in the triclinic space group P consists of six approximately square planar Pd(II)S4 centers, which are inter-connected through twelve µ2-bridging benzyl thiol-ate groups. The Pd⋯Pd contacts range from 3.0892 (2) to 3.1609 (2) Šand can be considered as weakly bonding. The unit cell of Pd6 contains also a co-crystallized anthracene-9,10-dione mol-ecule.

Crystal structure of 2-[bis(benzylsulfanyl)methyl]-6-methoxyphenol.

The title compound, C22H22O2S2, 1, represents an example of an ortho-vanillin-based functionalized di-thio-ether, which could be useful as a potential chelating ligand or bridging ligand for coordination chemistry. This di-thio-acetal 1 crystallizes in the ortho-rhom-bic space group Pbca. The phenyl rings of the benzyl groups and that of the vanillin unit form dihedral angles of 35.38 (6) and 79.77 (6)°, respectively. The crystal structure, recorded at 100 K, displays both weak intra-molecular O-H⋯O and inter-molecular O-H⋯S hydrogen bonding.

Synthesis of novel S-linked dihydroartemisinin derivatives and evaluation of their anticancer activity.

We report herein the synthesis and anticancer activity of a set of novel S-linked artemisinins bearing an aliphatic/aromatic/heterocyclic nucleus as a substituent on the sulfur. The compounds were prepared from artemisinin via its lactol-form by an acid-catalyzed condensation of the desired thiol with the lactol. Both the C-10-α- and ß-configured thiol ethers were synthesized with a view to making them available for the anticancer activity evaluation using a variety of cell lines. The results show that many of the synthetic derivatives studied possessed good potential as anticancer agents. In order to draw more information on the origin of the anticancer activity, one of the compounds (9a), that showed a broad-spectrum activity in terms of reducing the viability of most of the cell lines studied, in particular proven to be most effective against Prostate (PC-3) cells, was studied in detail to find the underlying mechanism of its action by MTT assay, immunoblotting, flow cytometry and microscopy. Pretreatment of the PC-3 cells with N-acetyl cysteine affected the efficacy of 9a, suggesting the role of reactive oxygen species in reducing their viability. Cell cycle analysis showed increase in G1 phase that was indicative of G1 cell cycle arrest. Wound healing assay revealed anti-migratory effect of 9a Quantitative PCR and western blot analysis showed changes in the gene expression of PCNA, E2F1, Pin1, cyclinD1, phospho-c-jun, c-Myc, eIF4E and other genes involved in proliferation and maintaining the transformed phenotype of prostate cancer cells. Here we report the anti-proliferative property of 9a with a vital and potent target(s) in prostate cancer cells with one of such targets being Pin1 belonging to the parvulin family of PPIases. The results suggest that 9a could be a promising agent in combating prostate cancer.

Highly sensitive and selective turn-on fluorescent chemosensors for Hg2+ based on thioacetal modified pyrene.

This work reports a facile strategy for the synthesis of water-soluble fluorescent probes Pyr1 and Pyr2, which have carboxyl and hydroxyl group in the side chain of thioacetal moiety, respectively. Pyr1-2 exhibit exclusively selective turn-on fluorescence response towards Hg2+ over other cations, based on intramolecular charge transfer (ICT) mechanism. Upon addition of Hg2+, the thioacetal moiety in Pyr1-2 can be converted to aldehyde group, which is confirmed by 1H NMR titrations. The detection limits for Pyr1-2 are less than 1.80nM in aqueous media, lower than the maximum allowable level of Hg2+ in drinking water by EPA. Moreover, Pyr2 have been successfully used for fluorescence imaging of Hg2+ in living cells, demonstrating potential application in biological science.

Crystal structure of 2-cyano-3,3-bis-(ethyl-sulfan-yl)-N-o-tolyl-acryl-amide.

In the mol-ecule of the title compound, C15H18N2OS2, the central S2C=C(CN)C moiety is planar (r.m.s. deviation = 0.029 Å). The C=O and C-CN groups are trans to each other across their common C-C bond. In the crystal, one classical and two 'weak' hydrogen bonds combine with borderline N⋯N and S⋯S contacts to form layers parallel to (10-2). One ethyl group is disordered over two positions with relative occupancy 0.721/0.279 (7).