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Oxidation of a series of tetrathiafulvalene (TTF) vinylogues is investigated in acetonitrile and dichloromethane. Two single-electron transfers or one two-electron process was observed depending on the substituent and the solvent. It is shown that the unusual redox behavior for short-length TTF vinylogues is due to substantial conformation changes concerted with the electron transfers.

The electrochemical synthesis of new extended TTFs (tetrathiafulvalenes) is possible from 1,4-dithiafulvalenes through the dimerization of two cation radicals. This procedures allows for the synthesis of new vinylogous TTFs which have applications as organic conductors and can easily become dication species through oxidation. This method may be extended to the synthesis of conducting charge transfer salts.

Byline: N. Bellec, A. Faucheux, F. Hauquier, D. Lorcy, B. Fabre Different Si(111) surfaces covalently derivatised with alkyl monolayers terminated by redox-active centres, namely reversibly oxidisable ferrocene and tetrathiafulvalene (TTF), and electrochemically polymerisable pyrrole, have been prepared. Ferrocene and pyrrole were attached to the silicon surface using carbodiimide coupling between an amino-substituted derivative and a pre-assembled acid-terminated monolayer. TTF monolayers were produced from the direct reaction of an alcohol-substituted TTF derivative with hydrogen-terminated Si(111). The electrochemical oxidation of the pyrrole-modified surface in the presence of pyrrole yielded strongly adherent and smooth conducting polypyrrole films, the thickness of which could be easily controlled from the consumed electrical charge. The hybrid polypyrrole/pyrrole monolayer/Si(111) junction showed the expected metal-insulator-semiconductor (MIS) diode behaviour with a rectification factor at 2 V of ca. 280. The electrochemical characteristics of the ferrocene- and TTF-modified surfaces evidenced a single and two one-electron system(s) respectively, located at potentials very close to those observed with the electroactive compounds in solution. The surface coverages of ferrocene and TTF were 0.23 and 0.15 per surface silicon atom respectively. Moreover, the rate constants of electron transfer were found to be 50 s−1 and 25 s−1 for the ferrocene and TTF monolayers respectively.

Dithiadiazafulvalenes (DTDAFs) as compared to tetrathiafulvalenes (TTFs), appear to be a bit of an outsider in the field of molecular conductors. These unrecognized precursors of organic materials present striking properties as compared to their sulfur analogues the TTFs, due to the presence of the nitrogen atom into the fulvalene skeleton.

Optical properties of the quasi-two-dimensional single-component molecular Mott insulator [Au(Et-thiazdt)2] (Et-thiazdt = N-ethyl-1,3-thiazoline-2-thione-4,5-dithiolate) have been investigated under pressure at room temperature. At 1.5 GPa, [Au(Et-thiazdt)2] undergoes an insulator to metal transition (IMT). Optical conductivity spectra exhibit a clear Drude peak at high pressure. In addition, we observed a clear anisotropy of pressure-induced modifications of the electronic structure. With increasing pressure, along the molecule stacks, a strong increase of the spectral weight below 1 eV is observed, while in the transverse direction, it remains barely constant with a redistribution from midinfrared to low energy. Besides the increase of the singly occupied molecular orbital (SOMO) bandwidth, calculations show that the SOMO-1 bands cross the Fermi level at the transition. Moreover, we have calculated the optical conductivity as a function of pressure to provide a picture of the compound physics under 1 eV. Our results indicate that the pressure-induced IMT is simultaneously due to a bandwidth and a band-filling phenomenon that imply both Mott physics and uncorrelated charge carriers. [ABSTRACT FROM AUTHOR]

Bi- and trimetallic platinum(bipyridine)(dithiolene) complexes involving different organic linkers between the redox active platinum(dithiolene) moieties have been synthesized and studied by electrochemistry and spectroelectrochemistry. Cyclic voltammetry experiments carried out on these multinuclear complexes in dichloromethane using [NBu 4 ][PF 6 ] as the supporting salt show only one oxidation process involving the metallacycles. Nevertheless, spectro-electrochemical studies, carried out under the same conditions, show a different evolution of the spectra during oxidation depending on the position of the metallacycles on the phenyl ring. For instance, only the 1,3-disubtituted (Pt21,3-P) and 1,3,5-trisubstituted (Pt31,3,5-P) complexes show the growth of an absorption band in the NIR region upon oxidation while it was not observed for the other complexes. In contrast, electrochemical studies carried out using the poorly coordinating supporting electrolyte, [Na][B(C 6 H 4 (CF 3 ) 2 ) 4 ], indicate sequential oxidation of the redox centers with Δ E values varying according to the nature of the bridge and the distance between metal centers. For all the investigated multinuclear complexes, spectro-electrochemical experiments performed in the presence of [Na][B(C 6 H 4 (CF 3 ) 2 ) 4 ] show an absorption band in the NIR region consistent with appreciable electrostatic effects and charge delocalization in the mixed valent intermediates.

Cancer and infection diseases pose severe threats to public health worldwide stressing the need for more effective and efficient treatments. Thus, the search for broad-spectrum activity drugs seems justifiable and urgent. Herein, we investigate the anticancer and antitrypanosomatid (anti-Trypanosoma cruzi) activities of eight monoanionic metal bis(dithiolene) complexes, [Ph 4 P][M(R-thiazdt) 2 ] with M n+  = Au 3+ , Pt 2+ , Pd 2+ , Ni 2+ , containing N-alkyl-1,3-thiazoline-2-thione dithiolene ligands (R-thiazdt) with different alkyl groups (R = Et, tBu). Compared to auranofin (AF) and cisplatin (CP), two reference drugs in clinical use, all complexes showed high anticancer activities against A2780 ovarian cancer cells (IC 50 values of 0.6-3.8 μM) some also being able to overcome CP resistance in A2780cisR cells. The selectivity index (SI), the IC 50 values on normal cells (HDF) vs. A2780 cells, indicated good anticancer specificity (SI > 3) for most of the complexes but with clinical relevance for [Ph 4 P][Pd(tBu-thiazdt) 2 ] (SI = 10). All complexes showed relevant antitrypanosomatid activities (IC 50 values of 2.6-5.8 μM) some even exhibiting lower IC 50 values than the reference drug nifurtimox (NFX). The mechanism of cell death seemed to be mediated mainly by the formation of reactive oxygen species (ROS), although to lesser extent for the gold complexes but superior to AF. Although ROS play a role in the main apoptotic pathways, cell death by apoptosis was not evident as shown by the caspase-3/7 assay and the morphological cell features studies by electron microscopy (SEM). Results obtained evidenced that [Ph 4 P][Pt(tBu-thiazdt) 2 ] and [Ph 4 P][Pd(tBu-thiazdt) 2 ] complexes might have potential as novel anticancer and antitrypanosomatid agents as alternatives to current therapeutics., Competing Interests: Declaration of competing interest Lorcy Dominique reports was provided by UNMR CNRS-Université de Rennes. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Monoanionic gold bis(dithiolene) complexes were recently shown to display activity against ovarian cancer cells, Gram-positive bacteria, Candida strains and the rodent malaria parasite, P. berghei . To date, only monoanionic gold(III) bis(dithiolene) complexes with a thiazoline backbone substituted with small alkyl chains have been evaluated for biomedical applications. We now analyzed the influence of the length and the hydrophobicity vs. hydrophilicity of these complexes' alkyl chain on their anticancer and antiplasmodial properties. Isomer analogues of these monoanionic gold(III) bis(dithiolene) complexes, this time with a thiazole backbone, were also investigated in order to assess the influence of the nature of the heterocyclic ligand on their overall chemical and biological properties. In this report we present the total synthesis of four novel monoanionic gold(III) bis(dithiolene) complexes with a long alkyl chain and a polyoxygenated (PEG) chain aiming to improve their solubility and biological properties. Our results showed that the complexes with a PEG chain showed promising anticancer and antiplasmodial activities beside improved solubility, a key parameter in drug discovery and development.

Neutral radical bis(dithiolene) gold complexes [Au(dt) 2 ]˙ are known to exhibit a strong absorption in the 1400-2000 nm NIR absorption range. Here, we demonstrate that the NIR signature of mixed-ligand bis(dithiolene) gold complexes [Au(dt A )(dt D )]˙ associating two different dithiolene, dt A and dt D , is found at higher energy, out of the range of the homoleptic analogs [Au(dt A ) 2 ]˙ and [Au(dt D ) 2 ]˙, in the looked-after NIR-II 1000-1400 nm absorption range. An efficient synthetic approach towards precursor mixed-ligand monoanionic gold bis(dithiolene) complexes [Au(dt A )(dt D )] -1 is reported. Using this strategy, no symmetrical complexes are formed and, upon electrocrystallization, no scrambling was observed in solution, allowing for the isolation of radical gold bis(dithiolene) complex such as [Au(bdt)(Et-thiazdt)]˙ (bdt: benzene-1,2-dithiolate; Et-thiazdt: N -ethyl-thiazoline-2-thione-3,4-dithiolate), which behaves as a single-component conductor. It is shown from theoretical calculations that the spin polarization induced by electron repulsions leads to a strong localization of the spin-orbitals, and provides a sound basis to understand, (i) the different ligand-based oxidation potentials, (ii) the NIR optical absorption at notably higher energies and (iii) the larger potential difference of the two redox processes than in the parent symmetric complexes. The solid-state properties of the radical complex [Au(bdt)(Et-thiazdt)]˙ are the consequence of a strongly 1D electronic structure with weakly dimerized chains and electronic localization favoring a semiconducting behavior, stable under pressures up to 18.2 GPa. Altogether, the versatility of the preparation method of [Au(dt A )(dt D )] -1 salts opens the route for a wide library of different mixed-ligand radical complexes [Au(dt A )(dt D )]˙ with simultaneously an adaptable absorption in the NIR-II range and the rich structural chemistry of single-component conductors., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The synthesis and characterization of two bis(dithiolene) proligands involving heteroatomic linkers such as 1,4-dithiine and dihydro-1,4-disiline between the two protected dithiolene moieties are described. Two bimetallic complexes involving these heteroatomic bridges between two redox active bis(cyclopentadienyl)molybdenum dithiolene moieties have been synthesized and characterized by electrochemistry, spectroelectrochemistry, and their properties rationalized with (TD-)DFT. Cyclic voltammetry experiments show sequential oxidation of the two redox centers with Δ E values between successive one-electron transfers varying according to the nature of the bridge. Depending on the nature of the heteroatomic bridge, the bis-oxidized complexes exhibit either a diradical character with both radicals essentially localized on the metallacycles, or a closed-shell dicationic state.

Benzene-1,2,4,5-tetrathiolate (btt) has been used as a bridging ligand to prepare a redox active (molybdenocene dithiolene)-based bimetallic complex Cp 2 Mo(btt)MoCp 2 , which exhibits four successive electron transfers up to the tetracation. Spectro-electrochemical investigations together with DFT and TD-DFT calculations evidence that the two electroactive MoS 2 C 2 metallacycles are electronically coupled in the monocationic as in the dicationic state. Two salts of the dication [Cp 2 Mo(btt)MoCp 2 ] 2+ have been structurally characterized with PF 6 - and HSO 4 - counterions, showing different chair or boat conformations associated with variable folding angles of the two MoS 2 C 2 metallacycles along the S-S hinge. The bis-oxidized dicationic complex exhibits a diradical character, with both radicals essentially localized on the metallacycles and with antiferromagnetic coupling evidenced from magnetic susceptibility measurements., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The prototypical [Ni(dmit) 2 ] complex (dmit: 1,3-dithiole-2-thione-4,5-dithiolate) is modified here by combining the N-R substitution found in [Ni(R-thiazdt) 2 ] complexes (R-thiazdt: N -alkyl-thiazoline-2-thione-4,5-dithiolate) and the selone substitution found in [Ni(dmiSe) 2 ] complex (dmiSe: 1,3-dithiole-2-selone-4,5-dithiolate) to give a novel N -methyl substituted, radical anionic complex formulated as [Ni(Me-thiazSe-dt) 2 ] 1- (Me-thiazSe-dt: N -methyl-thiazoline-2-selone-4,5-dithiolate). Both this anionic complex and its mixed-valence Et 4 N + salt crystallize with a rare cis arrangement of the two dithiolene ligands around the Ni atom. In the 1 : 2 [Et 4 N][Ni(Me-thiazSe-dt) 2 ] 2 salt, the complexes organize into dimerized chains well isolated from each other, giving the salt a strong one-dimensional character. It shows however a high RT conductivity of 4.6 S cm -1 and small activation energy of 33 meV, indicating a possible Mott insulator behavior, which is not suppressed under pressures up to 10 GPa.

Block copolymer micelles (BCMs) can be used to improve the solubility of lipophilic drugs and increase their circulation half-life. Hence, BCMs assembled from MePEG- b -PCL were evaluated as drug delivery systems of gold(III) bis(dithiolene) complexes (herein AuS and AuSe) to be employed as antiplasmodial drugs. These complexes exhibited remarkable antiplasmodial activity against liver stages of the Plasmodium parasite, and low toxicity in a model of zebrafish embryos. To improve the complexes' solubility, BCMs were loaded with AuS, AuSe, and the reference drug primaquine (PQ). PQ-BCMs (D berghei = 50.9 ± 2.8 nm), AuSe-BCMs (D h = 87.1 ± 9.7 nm), and AuS-BCMs (D h = 87.1 ± 9.7 nm), and AuS-BCMs (D h = 72.8 ± 3.1 nm) were obtained with a loading efficiency of 82.5%, 55.5%, and 77.4%, respectively. HPLC analysis and UV-Vis spectrophotometry showed that the compounds did not suffer degradation after encapsulation in BCMs. In vitro release studies suggest that AuS/AuSe-BCMs present a more controlled release compared with PQ-loaded BCMs. The antiplasmodial hepatic activity of the drugs was assessed in vitro and results indicate that both complexes present higher inhibitory activity than PQ, although encapsulated AuS and AuSe presented lower activity than their non-encapsulated counterparts. Nevertheless, these results suggest that the use of BCMs as delivery vehicles for lipophilic metallodrugs, particularly AuS and AuSe, could enable the controlled release of complexes and improve their biocompatibility, constituting a promising alternative to conventional antimalarial treatments.

Highly conducting, mixed-valence, multi-component nickel bis( diselenolene ) salts were obtained by electrocrystallization of the monoanionic species [Ni(Me-thiazds) 2 ] -1 (Me-thiazds: N -methyl-1,3-thiazoline-2-thione-4,5-diselenolate), with 1:2 and 1:3 stoichiometries depending of the counter ion used (Et 4 N + and n Bu 4 N + vs Ph 4 P + , respectively). This behavior strongly differs from that of the corresponding monoanionic dithiolene complexes whose oxidation afforded the single component neutral species. This provides additional rare examples of mixed-valence conducting salts of nickel diselenolene complexes, only known in two examples with the dsit (1,3-dithiole-2-thione-4,5-diselenolate) and dsise (1,3-dithiole-2-selone-4,5-diselenolate) ligands. The mixed-valence salts form highly dimerized or trimerized bi- and trimetallic units, rarely seen with such nickel complexes. Transport measurements under a high pressure (up to 10 GPa) and band structure calculations confirm the semiconducting character of [Ph 4 P][Ni(Me-thiazds) 2 ] 3 and the quasi metallic character of [Et 4 N][Ni(Me-thiazds) 2 ] 2 and [NBu 4 ] x [Ni(Me-thiazds) 2 ] 2 salts (0 < x < 1).

The biological properties of sixteen structurally related monoanionic gold (III) bis(dithiolene/ diselenolene) complexes were evaluated. The complexes differ in the nature of the heteroatom connected to the gold atom (AuS for dithiolene, AuSe for diselenolene), the substituent on the nitrogen atom of the thiazoline ring (Me, Et, Pr, iPr and Bu), the nature of the exocyclic atom or group of atoms (O, S, Se, C(CN) 2 ) and the counter-ion (Ph 4 P + or Et 4 N + ). The anticancer and antimicrobial activities of all the complexes were investigated, while the anti-HIV activity was evaluated only for selected complexes. Most complexes showed relevant anticancer activities against Cisplatin-sensitive and Cisplatin-resistant ovarian cancer cells A2780 and OVCAR8, respectively. After 48 h of incubation, the IC 50 values ranged from 0.1-8 μM (A2780) and 0.8-29 μM (OVCAR8). The complexes with the Ph 4 P + ([ P ]) counter-ion are in general more active than their Et 4 N + ([ N ]) analogues, presenting IC 50 values in the same order of magnitude or even lower than Auranofin. Studies in the zebrafish embryo model further showed that, despite their marked anticancer effect, the complexes with [ P ] counter-ion exhibited low in vivo toxicity. In general, the exocyclic exchange of sulfur by oxygen or ylidenemalononitrile (C(CN) 2 ) enhanced the compounds toxicity. Most complexes containing the [ P ] counter ion exhibited exceptional antiplasmodial activity against the Plasmodium berghei parasite liver stages, with submicromolar IC 50 values ranging from 400-700 nM. In contrast, antibacterial/fungi activities were highest for most complexes with the [ N ] counter-ion. Auranofin and two selected complexes [ P ][AuSBu(=S)] and [ P ][AuSEt(=S)] did not present anti-HIV activity in TZM-bl cells. Mechanistic studies for selected complexes support the idea that thioredoxin reductase, but not DNA, is a possible target for some of these complexes. The complexes [ P ] [AuSBu(=S)], [ P ] [AuSEt(=S)], [ P ] [AuSEt(=Se)] and [ P ] [AuSeiPr(=S)] displayed a strong quenching of the fluorescence intensity of human serum albumin (HSA), which indicates a strong interaction with this protein. Overall, the results highlight the promising biological activities of these complexes, warranting their further evaluation as future drug candidates with clinical applicability.

Two selenated analogues of the all-sulfur single-component molecular conductor [Ni(Et-thiazdt) 2 ] (Et-thiazdt = N -ethylthiazoline-2-thione-4,5-dithiolate) have been prepared from their precursor radical-anion complexes. Replacement of the thione by a selenone moiety gives the neutral [Ni(Et-thiaz Se dt) 2 ] complex. It adopts an unprecedented solid-state organization (for neutral nickel complexes), with the formation of perfectly eclipsed dimers and very short intermolecular Se···Se contacts (81% of the van der Waals contact distance). Limited interactions between dimers leads to a large semiconducting gap and low conductivity (σ RT = 1.7 × 10 -5 S cm -1 ). On the other hand, going from the neutral [Ni(Et-thiazdt) 2 ] dithiolene complex to the corresponding [Ni(Et-thiaz ds ) 2 ] diselenolene complex gives rise to a more conventional layered structure built out of uniform stacks of the diselenolene complexes, different, however, from the all-sulfur analogue [Ni(Et-thiazdt) 2 ]. Band structure calculations show an essentially 1D electronic structure with large band dispersion and a small HOMO-LUMO gap. Under high pressures (up to 19 GPa), the conductivity increases by 4 orders of magnitude and the activation energy is decreased from 120 meV to only 13 meV, with an abrupt change observed around 10 GPa, suggesting a structural phase transition under pressure.

The anticancer, antimicrobial and antiplasmodial activities of six gold(iii) bis(dithiolene) complexes were studied. Complexes 1-6 showed relevant anticancer properties against A2780/A2780cisR ovarian cancer cells (IC50 values of 0.08-2 μM), also being able to overcome cisplatin resistance in A2780cisR cells. Complex 1 also exhibited significant antimicrobial activity against Staphylococcus aureus (minimum inhibitory concentration (MIC) values of 12.1 ± 3.9 μg mL-1) and both Candida glabrata and Candida albicans (MICs of 9.7 ± 2.7 and 19.9 ± 2.4 μg mL-1, respectively). In addition, all complexes displayed antiplasmodial activity against the Plasmodium berghei parasite liver stages, even exhibiting better results than the ones obtained using primaquine, an anti-malarial drug. Mechanistic studies support the idea that thioredoxin reductase, but not DNA, is a possible target of these complexes. Complex 1 is stable under biological conditions, which would be important if this compound is ever to be considered as a drug. Overall, the results obtained evidenced the promising biological activity of complex 1, which might have potential as a novel anticancer, antimicrobial and antiplasmodial agent to be used as an alternative to current therapeutics.

Introduction of hydrogen bonding (HB) interactions in single component conductors derived from nickel and gold bis(dithiolene) complexes is explored with the 2-alkylthio-1,3-thiazole-4,5-dithiolate (RS-tzdt) with R = CH 2 CH 2 OH through the preparation of the neutral [Ni(HOEtS-tzdt) 2 ] 0 (closed-shell) and [Au(HOEtS-tzdt) 2 ]˙ (radical) complexes. At variance with many other radical gold dithiolene complexes which have a strong tendency to dimerize in the solid state, [Au(HOEtS-tzdt) 2 ]˙ crystallizes into uniform stacks interconnected by strong O-HN HB involving the nitrogen atom of the thiazole ring. [Au(HOEtS-tzdt) 2 ]˙ is isostructural with its neutral, closed-shell nickel analog [Ni(HOEtS-tzdt) 2 ] 0 , a rare situation in this metal bis(dithiolene) chemistry. It demonstrates how the strength of the HB directing motif can control the overall structural arrangement to stabilize the same structure despite a different electron count. The nickel complex behaves as a band semiconductor with weak room temperature conductivity (1.6 × 10 -5 S cm -1 ), while the gold complex is described as a Mott insulator with a three orders of magnitude improved conductivity (6 × 10 -2 S cm -1 ).