Biogenic Sulfur-Based Chalcogenide Nanocrystals: Methods of Fabrication, Mechanistic Aspects, and Bio-Applications.

Bio-nanotechnology has emerged as an efficient and competitive methodology for the production of added-value nanomaterials (NMs). This review article gathers knowledge gleaned from the literature regarding the biosynthesis of sulfur-based chalcogenide nanoparticles (S-NPs), such as CdS, ZnS and PbS NPs, using various biological resources, namely bacteria, fungi including yeast, algae, plant extracts, single biomolecules, and viruses. In addition, this work sheds light onto the hypothetical mechanistic aspects, and discusses the impact of varying the experimental parameters, such as the employed bio-entity, time, pH, and biomass concentration, on the obtained S-NPs and, consequently, on their properties. Furthermore, various bio-applications of these NMs are described. Finally, key elements regarding the whole process are summed up and some hints are provided to overcome encountered bottlenecks towards the improved and scalable production of biogenic S-NPs.

Investigation of chalcogen bioisosteric replacement in a series of heterocyclic inhibitors of tryptophan 2,3-dioxygenase.

Selenium is an underexplored element that can be used for bioisosteric replacement of lower molecular weight chalcogens such as oxygen and sulfur. More studies regarding the impact of selenium substitution in different chemical scaffolds are needed to fully grasp this element's potential. Herein, we decided to evaluate the impact of selenium incorporation in a series of tryptophan 2,3-dioxygenase (TDO2) inhibitors, a target of interest in cancer immunotherapy. First, we synthesized the different chalcogen isosteres through Suzuki-Miyaura type coupling. Next, we evaluated the isosteres' affinity and selectivity for TDO2, as well as their lipophilicity, microsomal stability and cellular toxicity on TDO2-expressing cell lines. Overall, chalcogen isosteric replacements did not disturb the on-target activity but allowed for a modulation of the compounds' lipophilicity, toxicity and stability profiles. The present work contributes to our understanding of oxygen/sulfur/selenium isostery towards increasing structural options in medicinal chemistry for the development of novel and distinctive drug candidates.

Chalcogen Bonds Involving Selenium in Protein Structures.

Chalcogen bonds are the specific interactions involving group 16 elements as electrophilic sites. The role of chalcogen atoms as sticky sites in biomolecules is underappreciated, and the few available studies have mostly focused on S. Here, we carried out a statistical analysis over 3562 protein structures in the Protein Data Bank (PDB) containing 18 266 selenomethionines and found that Se···O chalcogen bonds are commonplace. These findings may help the future design of functional peptides and contribute to understanding the role of Se in nature.

Charge Assisted S/Se Chalcogen Bonds in SAM Riboswitches: A Combined PDB and ab Initio Study.

In this study, we provide experimental (Protein Data Bank (PDB) inspection) and theoretical (RI-MP2/def2-TZVP level of theory) evidence of the involvement of charge assisted chalcogen bonding (ChB) interactions in the recognition and folding mechanisms of S-adenosylmethionine (SAM) riboswitches. Concretely, an initial PDB search revealed several examples where ChBs between S-adenosyl methionine (SAM)/adenosyl selenomethionine (EEM) molecules and uracil (U) bases belonging to RNA take place. While these interactions are usually described as a merely Coulombic attraction between the positively charged S/Se group and RNA, theoretical calculations indicated that the σ holes of S and Se are involved. Moreover, computational models shed light on the strength and directionality properties of the interaction, which was also further characterized from a charge-density perspective using Bader's "Atoms in Molecules" (AIM) theory, Non-Covalent Interaction plot (NCIplot) visual index, and Natural Bonding Orbital (NBO) analyses. As far as our knowledge extends, this is the first time that ChBs in SAM-RNA complexes have been systematically analyzed, and we believe the results might be useful for scientists working in the field of RNA engineering and chemical biology as well as to increase the visibility of the interaction among the biological community.

A Regioselective Synthesis of Novel Functionalized Organochalcogen Compounds by Chalcogenocyclofunctionalization Reactions Based on Chalcogen Halides and Natural Products.

The regioselective synthesis of novel functionalized condensed organochalcogen compounds by chalcogenocyclofunctionalization reactions based on chalcogen halides and the natural products thymol and carvacrol has been developed. The reactions of selenium dibromide with allyl thymol and allyl carvacrol proceeded in methylene chloride at room temperature in the presence of NaHCO3 affording bis[(7-isopropyl-4-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl] and bis[(4-isopropyl-7-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl] selenides in 90-92% yield. Similar sulfides were obtained in 70-72% yields by the reaction of sulfur dichloride in chloroform under reflux. Trihalotellanes containing the same organic moieties were synthesized from allyl thymol, allyl carvacrol and tellurium tetrachloride or tetrabromide in quantitative yields. Corresponding functionalized ditellurides were prepared in 91-92% yields by the reduction of the trichlorotellanes with sodium metabisulfite in two-phase solvent system. The comparison of reactivity of sulfur, selenium and tellurium halides in chalcogenocyclofunctionalization and distinguishing features of each reaction were discussed.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50 °C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe = 866.0 ppm), 125Te{1H} (δTe = 422.0 ppm) and 31P{1H} (δP = -1.0, -13.0 and -15.0 ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened in vitro and ex vivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

Synthesis of 2-Organylchalcogenopheno[2,3-b]pyridines from Elemental Chalcogen and NaBH4 /PEG-400 as a Reducing System: Antioxidant and Antinociceptive Properties.

An alternative method to prepare 2-organylchalcogenopheno[2,3-b]pyridines was developed by the insertion of chalcogen species (selenium, sulfur or tellurium), generated in situ, into 2-chloro-3-(organylethynyl)pyridines by using the NaBH4 /PEG-400 reducing system, followed by an intramolecular cyclization. It was possible to obtain a series of compounds with up to 93 % yield in short reaction times. Among the synthesized products, 2-organyltelluropheno[2,3-b]pyridines have not been described in the literature so far. Moreover, the compounds 2-phenylthieno[2,3-b]pyridine (3 b) and 2-phenyltelluropheno[2,3-b]pyridine (3 c) exhibited significant antioxidant potential in different in vitro assays. Further studies demonstrated that compound 3 b exerted an antinociceptive effect in acute inflammatory and non-inflammatory pain models, thus indicating the involvement of the central and peripheral nervous systems on its pharmacological action. More specifically, our results suggest that the intrinsic antioxidant property of compound 3 b might contribute to attenuating the nociception and inflammatory process on local injury induced by complete Freund's adjuvant (CFA).

Gold-based Inorganic Nanohybrids for Nanomedicine Applications.

Noble metal Au nanoparticles have attracted extensive interests in the past decades, due to their size and morphology dependent localized surface plasmon resonances. Their unique optical property, high chemical stability, good biocompatibility, and easy functionalization make them promising candidates for a variety of biomedical applications, including bioimaging, biosensing, and cancer therapy. With the intention of enhancing their optical response in the near infrared window and endowing them with additional magnetic properties, Au nanoparticles have been integrated with other functional nanomaterials that possess complementary attributes, such as copper chalcogenides and magnetic metal oxides. The as constructed hybrid nanostructures are expected to exhibit unconventional properties compared to their separate building units, due to nanoscale interactions between materials with different physicochemical properties, thus broadening the application scope and enhancing the overall performance of the hybrid nanostructures. In this review, we summarize some recent progresses in the design and synthesis of noble metal Au-based hybrid inorganic nanostructures for nanomedicine applications, and the potential and challenges for their clinical translations.

Dual Chalcogen-Chalcogen Bonding Catalysis.

The noncovalent S···O bonding interaction is an evolutionary force that has been smartly exploited by nature to modulate the conformational preferences of proteins. The employment of this type of weak noncovalent force to drive chemical reactions is promising yet remains largely elusive. Herein, we describe a dual chalcogen-chalcogen bonding catalysis strategy that the distinct chalcogen atoms simultaneously interact with two chalcogen-based electron donors to give rise to the catalytic activity, thus facilitating chemical reactions. Conventional approaches to the Rauhut-Currier-type reactions require the use of strongly nucleophilic Lewis bases as essential promoters. The implementation of this dual chalcogen-chalcogen bonding catalysis strategy allows the simultaneous Se···O bonding interaction between chalcogen-bonding donors and an enone and an alcohol, enabling the realization of the Rauhut-Currier-type reactions in a distinct way. The further implementation of a consecutive dual Se···O bonding catalysis approach enables the achievement of an initial Rauhut-Currier-type reaction to give an enone product which further undergoes an alcohol-addition induced cyclization reaction. This work demonstrates that the nearly linear chalcogen-bonding interaction can differentiate similar alkyl groups to give rise to regioselectivity. Moreover, the new strategy shows its advantage as it not only enables less reactive substrates working efficiently but tolerates inaccessible substrates using conventional methods.

"All-in-One" Theranostic Agent with Seven Functions Based on Bi-Doped Metal Chalcogenide Nanoflowers.

Most of the existing single-component nanostructures cannot provide comprehensive diagnostic information, and their treatment strategies always have to combine other therapeutics as a complementary for effective biomedical application. Here, we adopted a facile approach to design a theranostic nanoflower (NF) with robust efficacy for comprehensive tumor diagnosis and quadruple synergistic cancer therapy. The NF is equipped with a metallic hybrid of several functional elements and flower-like superstructures and thus shows excellent in vitro and in vivo theranostic performance. It shows high X-ray attenuation coefficiency for the Bi element, strong near-infrared (NIR) plasmon absorbance and singlet oxygen (1O2) generation ability for the Mo element, and great photothermal conversion efficiency (54.7%) because of enhanced photoabsorption of the petal structure. Moreover, the NF realizes a very high doxorubicin-loading efficiency (90.0%) and bimodal pH/NIR-responsive drug release, posing a promise as a controlled drug carrier. The NF also shows excellent performance at trimodal magnetic resonance/X-ray computed tomography/photoacoustic imaging for comprehensive tumor diagnosis. To our best knowledge, it is the first time that integrating at least seven functions into one biomedical nanomaterial for well-rounded tumor theranostics has been reported. This "all-in-one" NF opens a new perspective in developing novel and efficient multifunctional nanotheranostics.

Polyphenol-Assisted Exfoliation of Transition Metal Dichalcogenides into Nanosheets as Photothermal Nanocarriers for Enhanced Antibiofilm Activity.

Transition metal dichalcogenide (TMD) nanosheets have evoked enormous research enthusiasm and have shown increased potentials in the biomedical field. However, a great challenge lies in high-throughput, large-scale, and eco-friendly preparation of TMD nanosheet dispersions with high quality. Herein, we report a universal polyphenol-assisted strategy to facilely exfoliate various TMDs into monolayer or few-layer nanosheets. By optimizing the exfoliation condition of molybdenum disulfide (MoS2), the yield and concentration of as-exfoliated nanosheets are up to 60.5% and 1.21 mg/mL, respectively. This is the most efficient aqueous exfoliation method at present and is versatile for the choices of polyphenols and TMD nanomaterials. The as-exfoliated MoS2 nanosheets possess superior biomedical stability as nanocarriers to load antibiotic drugs. They show a high photothermal conversion effect and thus induce a synergetic effect of chemotherapy and photothermal therapy to harvest enhanced antibiofilm activity under near-infrared (NIR) light. All these results offer an appealing strategy toward the synthesis and application of ultrathin TMD nanosheets, with great implications for their development.

Chalcogen 'like-like' Interactions Involving Trisulphide and Triselenide Compounds: A Combined CSD and Ab Initio Study.

In this manuscript, we combined a search in the Cambridge Structural Database (CSD) and ab initio calculations (RI-MP2/def2-TZVPD level of theory) to analyze the ability of trisulphide and triselenide moieties to establish chalcogen 'like-like' interactions. A preliminary CSD inspection revealed two predominant structural patterns, depending on the anti or syn conformation adopted by the substituents of the S3/Se3 bridge, leading to bifurcated or double chalcogen bonding interactions, respectively. In order to analyze these two relevant structural motifs we have used a series of S and Se derivatives Ch3X2 (Ch = S and Se and X = H, F, CN, and CF3) which act as both electron donor (using the lone pairs) and acceptor (using the σ-holes) entities. Besides, we have carried out "atoms in molecules" (AIM) and natural bonding orbital (NBO) analyses to further describe and characterize the chalcogen bonding interactions described herein. As far as we know, chalcogen···chalcogen interactions involving trichalconides (S3/Se3) have not been previously described in literature a may be of great importance in the preparation and characterization of new solids based on this subclass of σ-hole bonding.

Functionalized Cu3BiS3 nanoparticles for dual-modal imaging and targeted photothermal/photodynamic therapy.

Multifunctional nano-biomaterials with the integration of diagnostic and therapeutic functions have shown great promise in improving the efficacy of cancer therapy. Herein, a new nanoplatform based on functionalized Cu3BiS3 nanoparticles (NPs) is fabricated for tumour-targeted combination phototherapy. The as-synthesized hydrophobic Cu3BiS3 NPs are modified with DSPE-PEG/DSPE-PEG-NH2, followed by the conjugation of the photosensitizer chlorin e6 (Ce6) and the target ligand folic acid (FA). The introduced Ce6 can further form a chelate complex with Gd3+. The rationally designed Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs, which have high physiological stability and good biocompatibility, can specifically target FA-receptor over-expressed tumour cells. The Cu3BiS3-PEG-(Ce6-Gd3+)-FA NPs exhibit effective dual-modal CT and MR imaging in the xenografted HeLa tumours. Importantly, excellent in vivo anti-tumour effects have been achieved by synergistic photothermal/photodynamic therapy using the multifunctional NPs. We expect that this versatile nanoplatform will play a role in exploring precise cancer diagnosis and therapy.

Recent Advances in Functional Polymer Decorated Two-Dimensional Transition-Metal Dichalcogenides Nanomaterials for Chemo-Photothermal Therapy.

Novel nanomaterials and advanced nanotechnologies continue to promote the fast development of new approaches for efficient tumor therapy. As an alternative choice to various traditional therapies, non-invasive photothermal therapy (PTT) has attracted significant attention mainly due to its low cost, highly localizing, specific tumor treatment and minimal side effects on healthy tissues. PTT induced by photo-absorbing agents which can absorb and convert the external NIR laser into heat to ablate tumors. Plenty of studies have shown the significant potential of PTT to treat tumors in future practical applications. However, PTT alone usually could not eradicate tumors considering the intensity of laser gradual attenuates in biological tissues and the heat generated tends to distribute inhomogeneous within tumors tissues. Combination of chemotherapy with photothermal therapy into one system for tumor therapy is an effective strategy to further improve the therapy efficiency. In this Minireview, we focus on the recent advances in constructing PTT therapeutic and multi-model combination therapeutic via integrating nanomaterials and functional polymers.

Contrasting Structural Reconstructions, Electronic Properties, and Magnetic Orderings along Different Edges of Zigzag Transition Metal Dichalcogenide Nanoribbons.

Two-dimensional transition metal dichalcogenides represent an emerging class of layered materials exhibiting various intriguing properties, and integration of such materials for potential device applications will necessarily invoke further reduction of their dimensionality. Using first-principles approaches, here we investigate the structural, electronic, and magnetic properties along the two different edges of zigzag MX2 (M = Mo, W; X = S, Se) nanoribbons. Along the M edges, we reveal a previously unrecognized but energetically strongly preferred (2 × 1) reconstruction pattern, which is universally operative for all the four systems (and possibly more), characterized by an elegant self-passivation mechanism through place exchanges of the outmost X and M edge atoms. In contrast, the X edges undergo a much milder (2 × 1) or (3 × 1) reconstruction for MoX2 or WX2, respectively. These contrasting structural preferences of the edges can be exploited for controlled fabrication of properly tailored transition metal dichalcogenide nanoribbons under nonequilibrium growth conditions. We further use the zigzag MoX2 nanoribbons to demonstrate that the Mo and X edges possess distinctly different electronic and magnetic properties, which are significant for catalytic and spintronic applications.

Two-Dimensional Disorder in Black Phosphorus and Monochalcogenide Monolayers.

Ridged, orthorhombic two-dimensional atomic crystals with a bulk Pnma structure such as black phosphorus and monochalcogenide monolayers are an exciting and novel material platform for a host of applications. Key to their crystallinity, monolayers of these materials have a 4-fold degenerate structural ground state, and a single energy scale EC (representing the elastic energy required to switch the longer lattice vector along the x- or y-direction) determines how disordered these monolayers are at finite temperature. Disorder arises when nearest neighboring atoms become gently reassigned as the system is thermally excited beyond a critical temperature Tc that is proportional to EC/kB. EC is tunable by chemical composition and it leads to a classification of these materials into two categories: (i) Those for which EC ≥ kBTm, and (ii) those having kBTm > EC ≥ 0, where Tm is a given material's melting temperature. Black phosphorus and SiS monolayers belong to category (i): these materials do not display an intermediate order-disorder transition and melt directly. All other monochalcogenide monolayers with EC > 0 belonging to class (ii) will undergo a two-dimensional transition prior to melting. EC/kB is slightly larger than room temperature for GeS and GeSe, and smaller than 300 K for SnS and SnSe monolayers, so that these materials transition near room temperature. The onset of this generic atomistic phenomena is captured by a planar Potts model up to the order-disorder transition. The order-disorder phase transition in two dimensions described here is at the origin of the Cmcm phase being discussed within the context of bulk layered SnSe.

Low-Temperature Growth of Two-Dimensional Layered Chalcogenide Crystals on Liquid.

The growth of high-quality two-dimensional (2D) layered chalcogenide crystals is highly important for practical applications in future electronics, optoelectronics, and photonics. Current route for the synthesis of 2D chalcogenide crystals by vapor deposition method mainly involves an energy intensive high-temperature growth process on solid substrates, often suffering from inhomogeneous nucleation density and grain size distribution. Here, we first demonstrate a facile vapor-phase synthesis of large-area high-quality 2D layered chalcogenide crystals on liquid metal surface with relatively low surface energy at a growth temperature as low as ∼100 °C. Uniform and large-domain-sized 2D crystals of GaSe and GaxIn1-xSe were grown on liquid metal surface even supported on a polyimide film. As-grown 2D GaSe crystals have been fabricated to flexible photodetectors, showing high photoresponse and excellent flexibility. Our strategy of energy-sustainable low-temperature growth on liquid metal surface may open a route to the synthesis of high-quality 2D crystals of Ga-, In-, Bi-, Hg-, Pb-, or Sn-based chalcogenides and halides.

Chalcogen bonding interactions between reducible sulfur and selenium compounds and models of zinc finger proteins.

Reducible sulfur and selenium (r-S/Se) compounds, defined as sulfur and selenium compounds not in the lowest -2 oxidation state (e.g., -1 to +6), release Zn(2+) from zinc-sulfur proteins such as zinc fingers (ZFs) and metallothionein. A series of density functional theory calculations was performed on donor-acceptor complexes between r-S/Se compounds and models of the Cys2His2, Cys3His and Cys4 ZF sites. These S⋯S/Se chalcogen bonding interactions consist of the donation of electron density from a S lone pair on the ZF model to a S/Se-X antibonding molecular orbital of the r-S/Se compound. The strength of the interaction was shown to be dependent upon the Lewis basicity of the ZF model (Cys4>Cys3His>Cys2His2) and the Lewis acidity of the r-S/Se compound as measured by the energy of the S/Se-X antibonding orbital. Interactions with the softer r-Se compounds were stronger than the r-S compounds, consistent with the greater reactivity of the former with ZF proteins.

Dynamic Control of Optical Response in Layered Metal Chalcogenide Nanoplates.

Tunable optical transitions in ultrathin layered 2-dimensional (2D) materials unveil the electronic structures of materials and provide exciting prospects for potential applications in optics and photonics. Here, we present our realization of dynamic optical modulation of layered metal chalcogenide nanoplates using ionic liquid (IL) gating over a wide spectral range. The IL gating significantly increased the tuning range of the Fermi level and, as a result, substantially altered the optical transitions in the nanoplates. Using heavily n-doped Bi2Se3 nanoplates, we substantially modulated the light transmission through the ultrathin layer. A tunable, high-transmission spectral window in the visible to near-infrared region has been observed due to simultaneous shifts of both the plasma edge and absorption edge of the material. On the other hand, optical response of multilayer MoSe2 flakes gated by IL has shown enhanced transmission in both positive and negative biases, which is consistent with their ambipolar electrical behavior. The electrically controlled optical property tuning in metal chalcogenide material systems provides new opportunities for potential applications, such as wide spectral range optical modulators, optical filters, and electrically controlled smart windows with extremely low material consumption.

Atomic layer deposition on 2D transition metal chalcogenides: layer dependent reactivity and seeding with organic ad-layers.

This commmunication presents a study of atomic layer deposition of Al2O3 on transition metal dichalcogenide (TMD) two-dimensional films which is crucial for use of these promising materials for electronic applications. Deposition of Al2O3 on pristine chemical vapour deposited MoS2 and WS2 crystals is demonstrated. This deposition is dependent on the number of TMD layers as there is no deposition on pristine monolayers. In addition, we show that it is possible to reliably seed the deposition, even on the monolayer, using non-covalent functionalisation with perylene derivatives as anchor unit.