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The synthesis of six 2,6-di(pyrazol-1-yl)pyridine derivatives bearing dithiolane or carboxylic acid tether groups is described: [2,6-di(pyrazol-1-yl)pyrid-4-yl]methyl (R)-lipoate (L1), 2-[(2,6-di(pyrazol-1-yl)pyridine)-4-carboxamido]ethyl (R)-lipoate (L2), 2-[(2,6-di(pyrazol-1-yl)pyridine)-4-carboxy]ethyl (R)-lipoate (L3), N-([2,6-di(pyrazol-1-yl)pyrid-4-ylsulfanyl]-2-aminoethyl (R)-lipoamide (L4), 2-[(2,6-di(pyrazol-1-yl)pyridine)-4-carboxamido]acetic acid (L5) and 2-[(2,6-di(pyrazol-1-yl)pyridine)-4-carboxamido]propionic acid (L6). The iron(ii) perchlorate complexes of all the new ligands exhibit gradual thermal spin-crossover (SCO) in the solid state above room temperature, except L4 whose complex remains predominantly high-spin. Crystalline [Fe(L6)2][ClO4]2·2MeCN contains three unique cation sites which alternate within hydrogen-bonded chains, and undergo gradual SCO at different temperatures upon warming. The SCO midpoint temperature (T1/2) of the complexes in CD3CN solution ranges between 208-274 K, depending on the functional group linking the tether groups to the pyridyl ring. This could be useful for predicting how these complexes might behave when deposited on gold or silica surfaces.

Water soluble metallic nanoparticles are being developed for a variety of roles ranging from catalysis to drug delivery and as potential contrast agents. We demonstrate direct synthesis of high-quality water-soluble Au, Ag, Pt, Pd, Cu and alloyed AuPt nanoparticles as well as ligand-exchange of FePt, cubic Pt and Au/Pt core/shell nanoparticles using bidentate dithiolane PEG as a universal ligand. Simple chemistry can greatly expand the applications of metal nanoparticles.

Injectable self-healing hydrogels have found broad applications in drug delivery, tissue engineering and controlled 3D cell culture. Recently, cyclic disulfides were found to be useful in cross-linking and stabilizing liposomes by disulfide exchange polymerization, benefiting from the enhanced reactivity of the disulfide bonds. Herein, we report an injectable self-healing hydrogel constructed from cross-linked F127 with thermo and pH dual responsivity. The rapid sol-gel transition ability at body temperature allows it to be used as an injectable hydrogel. And the increased reactivity of the disulfides of cyclic dithiolane due to the ring tension makes the hydrogel self-heal under not only alkaline conditions but also neutral or even mildly acidic conditions.

L-Lactides were polymerized in bulk at 120 or 160 °C with cyclic dibutyltin catalysts derived from 1,2-dimercaptoethane or 2-mercaptoethanol. Only linear chains having one benzyl ester and one OH-end group were obtained when benzyl alcohol was added. When L-lactides were polymerized with neat dibutyl-2-stanna-1,3-dithiolane, exclusively cyclic polylactides were formed even at 120 °C. The temperature, time and monomer/catalyst ratio (M/C) were varied. These results are best explained by a combination of ring-expansion polymerization and ring-extrusion of cyclic oligo- or polylactides with elimination of the cyclic catalyst. Neither syntheses of linear polylactides nor of cyclic lactides involved racemization up to 20 h at 160 °C.

To realize desirable functions in the rather complex biological systems, a suitable surface coating is desirable for gold nanoparticles, which plays an important role in their colloidal stability and biocompatibility. In this work, a novel multidentate PEGylated chitosan derivative was synthesized by conjugating PEG and dithiolane lipoic acid (LA) to the chitosan backbone. Under reduction conditions, gold nanoparticles (AuNPs) could be in situ formed by the electrostatic interaction between amino groups of the chitosan derivative and gold chloride ions (AuCl4−), with their surface covalently coated by the multidentate PEGylated chitosan via the disulfide bond from LA. After the surface modification, such AuNPs exhibited remarkable colloidal stabilities under extreme conditions, including high salt conditions and complex biological media containing serum. Moreover, the multidentate PEGylated chitosan also provided AuNPs with good biocompatibility and low cytotoxicity, resistance of protein adsorption and anti-phagocytosis by RAW 264.7 cells. This kind of AuNP was expected to be a promising platform for applications in nanomedicine.

The chiral ketene equivalent trans-2-methylene-1,3-dithiolane 1,3-dioxide has been prepared in racemic and enantiomerically pure form in four steps. The key step in the asymmetric synthesis utilised a Modena asymmetric oxidation of 2-benzyloxymethyl-1,3-dithiolane which gave the trans bis-sulfoxide with high diastereocontrol (91∶9 in favour of trans) and high enantiocontrol (>97% ee). The ketene equivalent shows high selectivity (>97∶3) in Diels–Alder reactions with a range of simple dienes (cyclopentadiene, furan, 1-methoxybutadiene, Danishefsky’s diene, 1-methoxycyclohexa-1,3-diene) and shows high reactivity as it is able to undergo cycloadditions with notoriously unreactive dienes (cyclohexa-1,3-diene, 90∶10 selectivity; 2H-pyran-2-one, 94∶6 selectivity). Dihydropyridines also participated in cycloaddition reaction but with only moderate selectivity (73∶27). The Diels–Alder adducts can be readily deprotected to return the carbonyl group using a two step sequence involving reduction followed by hydrolysis.

Surface engineering of nanoparticles plays an essential role in their colloidal stability, biocompatibility and interaction with biosystems. In this study, a novel multidentate zwitterionic biopolymer derivative is obtained from conjugating dithiolane lipoic acid and zwitterionic acryloyloxyethyl phosphorylcholine to the chitosan oligosaccharide backbone. Gold nanoparticles (AuNPs) modified by this polymer exhibit remarkable colloidal stabilities under extreme conditions including high salt conditions, wide pH range and serum or plasma containing media. The AuNPs also show strong resistance to competition from dithiothreitol (as high as 1.5 M). Moreover, the modified AuNPs demonstrate low cytotoxicity investigated by both MTT and LDH assays, and good hemocompatibility evaluated by hemolysis of human red blood cells. In addition, the intracellular fate of AuNPs was investigated by ICP-MS and TEM. It showed that the AuNPs are uptaken by cells in a concentration dependent manner, and they can escape from endosomes/lysosomes to cytosol and tend to accumulate around the nucleus after 24 h incubation but few of them are excreted out of the cells. Gold nanorods are also stabilized by this ligand, which demonstrates robust dispersion stability and excellent hemocompatibility. This kind of multidentate zwitterionic chitosan derivative could be widely used for stabilizing other inorganic nanoparticles, which will greatly improve their performance in a variety of bio-related applications.

We report on the fabrication of water-dispersible composite silica nanospheres covalently anchored with gold nanoparticles (AuNPs) possessing thermo-tunable spatial distributions at the outer periphery of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM) brushes. Starting from initiator-functionalized silica nanoparticles, surface-initiated atom transfer radical polymerization (ATRP) of N-isopropylacrylamide (NIPAM) afforded hybrid silica nanoparticles coated with PNIPAM brushes. The substitution reaction of halogen terminal groups of grafted PNIPAM chains with sodium azide and subsequent click reaction with 1,2-dithiolane-3-pentanoic acid-N-propargylamide afforded hybrid silica nanoparticles coated with 1,2-dithiolane end-capped PNIPAM brushes. AuNPs were then covalently anchored to the outer periphery of hybrid silica nanoparticles by utilizing strong chemisorption of surface-attached dithiolane moieties to AuNPs. Dynamic laser light scattering (LLS) measurements revealed that thermosensitive PNIPAM brushes at the surface of hybrid silica nanoparticles exhibit reversible thermo-induced collapse/swelling transitions, leading to the facile thermo-modulation of spatial distributions of AuNPs covalently attached at the periphery of composite silica nanospheres and thermo-reversible surface plasmon absorption band shift. The reported strategy of covalent assembly of AuNPs into well-defined composite nanospheres possessing thermo-tunable characteristics might be further exploited for colorimetric temperature sensing and responsive SERS detection purposes.

The selective signaling of hypochlorous acid by dithiolane-protected pyrene-aldehyde was investigated. Dithiolane derivative of pyrene-aldehyde was efficiently deprotected by hypochlorous acid to its corresponding aldehyde, which resulted in a prominent UV-vis and turn-on type fluorescence signaling. The signaling was not affected by the presence of other common alkali, alkaline earth metal ions, and anions. Interference from Hg2+ ions could be successfully circumvented by using Chelex-100 resin. Dithiolane also provided selectivity toward hypochlorous acid over other commonly used oxidant of hydrogen peroxide.

Thiorhodamine-based chemodosimeter A, a disulfide linked dimer, was designed for Hg2+ recognition by virtue of the strong affinity of mercury for sulfur. Spectroscopic results reveal that chemodosimeter A exhibits real-time responses, and high sensitivity and selectivity for Hg2+ in comparison to other cations. These properties are mechanistically ascribed to the transfer from rhodamine spirolactam to the thiazoline-derived open-ring rhodamine via Hg2+ induced desulfurization. The in vitro recognition of Hg2+ in living cells pretreated with A was examined, showing that the concentration of Hg2+ that could be imaged reaches the safety limit for human beings.

We have investigated the potential of the dithiolane ring to anchor organic compounds on the surface of CdSe–ZnS core–shell quantum dots. In particular, we have synthesized three monomeric ligands, incorporating an azobenzene chromophore and a single dithiolane anchor in their molecular skeleton, as well as a polymeric ligand with multiple chromophoric labels and anchoring groups. All compounds co-adsorb on the surface of preformed quantum dots, together with their native tri-n-octylphosphine oxide surfactants, when chloroform dispersion of the organic ligands and the inorganic nanoparticles are heated under reflux for 24–72 h. The reaction time dictates the average number of azobenzene chromophores incorporated in the final assemblies, which can range from 6 up to 92. However, the modified quantum dots retain a substantial hydrophobic character and are not soluble in water, despite the presence of hydrophilic poly(ethylene glycol) chains in three of the four dithiolane ligands. The adsorbed azobenzene chromophores can be switched from trans to cis configurations with ultraviolet stimulations. The photochemical process is thermally reversibly and, in the case of the polymeric ligand, results in the photomodulation of the luminescence intensity of the nanostructured construct

Incorporation of 2-phenyl-1,3-dithiane 1 into ZSM-5 generated 1,2-dithiolane radical cation 2·+, the EPR spectrum of which shows an orthorhombic powder pattern (g1 = 2.0293, g2 = 2.0193, g3 = 2.0030); each g component showed a 1:4:6:4:1 pattern (a1 = 10.5, a2 = 9.3 and a3 = 9.2 G) due to coupling to four equivalent 1H nuclei, suggesting that the pseudo-axial and –equatorial α-protons undergo conformational equilibration whereas the sulfur centers are held stationary on the EPR time scale.

Alkene–dioxolane alternating copolymers 1 and 4, formed from ethane-1,2-diol and the corresponding alkene–carbon monoxide copolymers, undergo transketalisation reactions with ethane-1,2-dithiol, propane-1,3-dithiol and sulfanylethanol to yield novel dithiolane-, dithiane- and oxathiolane-containing polymers 6, 8, 9, 11 and 12.

Reaction of benzenethiol with the 1,3-dithiolane 1,3-dioxides 3a–f gave the 1,4-dithiane 1-oxides 4–5, the αβ-unsaturated sulfoxides 6–9, the ring-opening products 10–11 and various reduction products. Addition of benzenethiol, malononitrile, diethyl malonate or 2-mercapto-4,5-dihydrothiazole to the double bonds of the 2-alkenyl-1,3-dithiolane 1,3-dioxides 3g–h was performed with methylmagnesium chloride in methanol. Addition of methanol or an allyl group to the dioxide 3h occurred regioselectively to give the 1,3-dithiolane 1-oxide 19 or the 1,3-dithiolane 20.

Montmorillonite KSF at room temperature without solvent catalyses the synthesis of dithiolanes and dithianes from carbonyl compounds; chemoselectivity in dithiane and dithiolane formation is observed between aromatic aldehydes and ketones and between aromatic and aliphatic aldehydes.

A number of complementary synthetic approaches to the β-thiolactone intermediate 9 for elaboration to the novel 1,3-dioxo-1,2-dithiolane moiety 6 found in the antitumour antibiotic substance leinamycin 1 are described.Thus, deprotection of the benzylthio ether produced from 3-methylbut-2-enoic acid and toluene-α-thiol, leads to the mercapto acid 12 which on cyclisation produces the thiolactone 13. α-Methylation of the thiolactone 13, followed by α-oxygenation then gives rise to the substituted β-thiolactone 9. The β-thiolactone 9 is also produced when: (i) the sodium glycidate 17 is stirred with sodium sulfide leading to 18, followed by thiolactonisation; (ii) thioacetone is treated with the ketene derived from 2-acetoxypropanoyl chloride; and (iii) by irradiation of 3-methyl-2-trimethylsilyloxybut-2-ene 22 with thiophosgene leading to 23, followed by hydrolysis.The β-thiolactone 9 is then converted in three steps into the 1,3-dioxo-1,2-dithiolane 6 by: (i) ring opening to the thioic acid 15, using hydrogen sulfide–triethylamine; (ii) ring closure of 15 to 8 in the presence of aqueous ferric chloride; and finally (iii) oxidation using dimethyldioxirane.Treatment of the ethyl glycidate 19 with disodium disulfide in hot ethanol for 3 days provides the 1,2-dithiolane 8 directly, but in low yields (11–15%).When the aforementioned reaction sequences are translated to the glycidate 24, derived from 4-methylcyclohex-3-enone and α-chloropropanoic acid, the syntheses of the key intermediates 25, 27 and 26en route to the spiro-fused 1,3-dioxo-1,2-dithiolane 7 and leinamycin 1(see Scheme 1) were secured.

Singlet oxidation of 1,3-dithiolanes furnishes synthetically useful yields of 1,3-dithiolane 1-oxides. However, 2-ethyl-2-phenyl-1,3-dithiolane13 gave 2-ethyl-4-hydroxy-2-phenyl-1,3-dithiolane 19 as a major product.

Attempted thionation of diacylketene thioacetals derived from dimedone with dithiadiphosphetane disulphides (the Lawesson reagent and analogues) led to the expected monothioacylketene thioacetals only when the thioacetal sulphur atoms formed part of a dithiolane or dithiane ring. Acyclic analogues readily underwent dealkylation and further reactions, giving a 1,2-dithiole-3-thione derivative as the main isolated product. Reaction of an acyclic ketene thioacetal with P4S10–Et3N in acetonitrile at –30 °C permitted the isolation of the primary dealkylation product, a dimedonedithiocarboxylate, in 44% yield. A phenoxaphosphorine derivative was isolated as a by-product in the synthesis of bis(phenoxyphenyl)dithiaphosphetane disulphide.

The gas-phase thermolysis of the norbornadienespirodithiolane S-oxides (5) and (7) led to benzene, ethylene, and carbon disulphide as the major products, possibly involving carbon disulphide oxides as intermediates. Thermolyses of the related sulphones (9) or (14) led to completely different product patterns.

Methyl-lithium and lithium dimethylcuprate react with (±)-α-lipoic acid (1a) to give in low yield a mixture of ring-opened isomers (8:1) resulting from nucleophilic attack at the C-8 and C-6 sulphur atoms respectively of the dithiolane ring. Methylmagnesium iodide, dimethyl sodipmalonate, and 1 -pyrrolidin-1 -ylcyclohexene fail to open the ring of (1a). In contrast, trimethyl phosphite cleaves the S–S bond efficiently and regioselectively at the C-8 sulphur atom; the resultant product is degraded by way of a new conversion of phosphorothioate into thioether.

The compound [Cr(CO)5{S[graphic omitted]}] reacted with Li(NPri2), CS2, and [Et3O][BF4] to afford either [Cr(CO)5{SCHCHC(SEt)2}](1) or [Cr(CO)5{SC(SCHCH2)SEt}](2) depending upon the reaction conditions employed. The crystal structure of the co-ordinated thioaldehyde (1) was determined [orthorhombic, space group Pbcm, a= 11.530(5), b= 18.745(9), c= 7.889(4)A, and Z= 4] and refined to R= 0.040 and R′= 0.038. All the atoms except those of four axial CO ligands and some hydrogens lie in one plane.

Dienone–phenol rearrangement occurs in the reaction of an oxathiolane and dithiolane of 3-oxo-steroids with copper(II) bromide to give 4-methyl-19-norcholesta-1,3,5,(10)-trieno[1,2-b]-dihydroxathiine and -dihydrodithiine, respectively.