Design of New Bis(1,2,3-triazol-1-yl)methane-Based Nitrogen Ligands: Synthesis and Coordination Chemistry.

The reaction between bis(1,2,3-triazol-1-yl)methane derivatives and nBuLi and various aldehydes, yielded novel neutral ligand precursors incorporating alcohol functional groups. The resulting compounds exhibited distinct characteristics depending on the steric hindrance of the aldehyde employed. In instances where aromatic aldehydes were utilized, functionalization occurred at the methine group bridging both triazole rings. Conversely, the use of pivalic aldehyde prompted functionalization at the C5 position of the triazole ring. These compounds were subsequently employed as ligand precursors in the synthesis of organometallic aluminum and zinc complexes, yielding dinuclear complexes with high efficiency. The structural elucidation of all compounds was accomplished through spectroscopic methods and validated by X-ray crystallography. Preliminary catalytic investigations into the coupling reaction of cyclohexene oxide and CO2 revealed that aluminum and zinc complexes catalyzed the selective formation of polyether and polycarbonate materials, respectively.

Attaching Metal-Containing Moieties to ß-Lactam Antibiotics: The Case of Penicillin and Cephalosporin.

Procedures for the preparation of transition metal complexes having intact bicyclic cepham or penam systems as ligands have been developed. Starting from readily available 4-azido-2-azetidinones, a synthetic approach has been tuned using a copper-catalyzed azide-alkyne cycloaddition between 3-azido-2-azetinones and alkynes, followed by methylation and transmetalation to Au(I) and Ir(III) complexes from the mesoionic carbene Ag(I) complexes. This methodology was applied to 6-azido penam and 7-azido cepham derivatives to build 6-(1,2,3-triazolyl)penam and 7-(1,2,3-triazolyl)cepham proligands, which upon methylation and metalation with Au(I) and Ir(III) complexes yielded products derived from the coordination of the metal to the penam C6 and cepham C7 positions, preserving intact the bicyclic structure of the penicillin and cephalosporin scaffolds. The crystal structure of complex 28b, which has an Ir atom directly bonded to the intact penicillin bicycle, was determined by X-ray diffraction. This is the first structural report of a penicillin-transition-metal complex having the bicyclic system of these antibiotics intact. The selectivity of the coordination processes was interpreted using DFT calculations.

ß-Lactam and penicillin substituted mesoionic metal carbene complexes.

1,2,3-Triazolylidene MIC M-complexes (M = Au, Pd, Pt) having 2-azetidinones and penicillin G substituents at the triazole ring were prepared by CuAAC on 2-azetidinones having a terminal alkyne tethered at N1, followed by alkylation of the 1,2,3-triazole ring and transmetallation [Au(I), Pd(II) and Pt(II)]. The Au-MIC complexes efficiently catalyze the regioselective cycloisomerization of enynes, while the Pt-MIC complexes were efficient catalysts in hydrosilylation reactions.

Bio-Organometallic Derivatives of Antibacterial Drugs.

Overuse and misuse of antibacterial drugs has resulted in bacteria resistance and in an increase in mortality rates due to bacterial infections. Therefore, there is an imperative necessity of new antibacterial drugs. Bio-organometallic derivatives of antibacterial agents offer an opportunity to discover new active antibacterial drugs. These compounds are well-characterized products and, in several examples, their antibacterial activities have been studied. Both inhibition of the antibacterial activity and strong increase in the antibiotic activity of the parent drug have been found. The synthesis of the main classes of bio-organometallic derivatives of these drugs, as well as examples of the use of structure-activity relation (SAR) studies to increase the activity and to understand the mode of action of bio-organometallic antimicrobial peptides (BOAMPs) and platensimicyn bio-organometallic mimics is presented in this article.

Central (S) to Central (M=Ir, Rh) to Planar (Metallocene, M=Fe, Ru) Chirality Transfer Using Sulfoxide-Substituted Mesoionic Carbene Ligands: Synthesis of Bimetallic Planar Chiral Metallocenes.

Enantiopure bimetallic systems containing three different elements of chirality, namely a main-group-based chiral center (sulfur), a transition-metal chiral center (rhodium or iridium), and a planar chiral element (ferrocene or ruthenocene), have been prepared by a sequence of diastereoselective reactions. The chirality of the chiral sulfur center attached to C-5 of a 1,2,3-triazolylidene mesoionic carbene (MIC) ligand coordinated to a metal (Ir, Rh) was transferred through the formation of bimetallic complexes having a chiral-at-metal center and a planar chiral metallocene by C-H activation of the sandwich moiety (M=Fe, Ru). The sense of the planar chirality formed in this sequence of reactions depended on the nature of the ligands at the metal center of the starting complex. The configurations of these species were assigned on the basis of a combination of X-ray diffraction and CD measurements. An electrochemical study of these bimetallic complexes in coordinating solvents showed an equilibrium between the cationic complexes and the neutral species. The effect of the half-sandwich moiety on the oxidation potentials of the system is remarkable, producing notable cathodic displacements. DFT calculations support these findings.

Chiral Sulfur Functional Groups as Definers of the Chirality at the Metal in Ir and Rh Half-Sandwich Complexes: A Combined CD/X-ray Study.

Mesoionic carbenes (MICs) derived from triazolium salts that contain chiral sulfoxide or sulfoximine functional groups were used to construct enantiopure chiral-at-metal IrIII and RhIII half-sandwich complexes through the synthetic sequence of MIC complexation/C-H aromatic activation. The process was efficient and diastereoselective for the formation of enantiopure five-membered metallacycles. The use of the enantiomers of the chiral sulfur groups allowed us to prepare complexes that had opposite configurations at the metal center. Complete retention of the configuration at the metal center was observed during the formation of cationic IrIII complexes and upon insertion of alkynes into the IrIII -C bond, as demonstrated by a combined circular dichroism/X-ray study. These results point to a vicinal-assisted SN 1-like mechanism.

Gold(I)-Catalyzed Cycloisomerization-Dimerization Cascade of Benzene-Tethered 1,6-Enynes.

An unprecedented stereoselective domino reaction of 1,6-enynes with an aryl ring at C3-C4 in the presence of gold(I) catalysts at low temperature is described. This process involves a novel 5-exo-dig cycloisomerization-dimerization sequence to afford formal Diels-Alder adducts that undergo a smooth gold-catalyzed double bond migration at room temperature. In addition, the first examples of the gold mesoionic carbene mediated [2+2+2] cycloaddition of these enynes with benzaldehyde are reported.

Sulfur Groups Improve the Performance of Triazole- and Triazolium-Based Interaction Units in Anion Binding.

An NMR comparative study of 1,2,3-triazole and triazolium anion recognition units containing sulfoxide, sulfone, and sulfoximine groups at C4 unveils an enhancement in binding ability up to ≈1 kcal/mol in acetone-d6 correlated with a theoretical increase of H5 acidity. DFT calculations provide insight into binding modes in line with experimental data for these receptors.

Effect of a κ1-Bonded-M-1,2,3-triazole (M = Co, Ru) on the Structure and Reactivity of Group 6 Alkoxy (Fischer) Carbenes.

The [3 + 2] cycloaddition of two different metal-bound azides, [(Me4cyclam)CoII(N3)]ClO4 and (η5-C5H5)(dppe)RuII(N3), (dppe = Ph2PCH2CH2PPh2) with Cr(0) and W(0) (ethoxy)(alkynyl) Fischer carbenes has been efficiently used for the preparation of polymetallic metal-carbene complexes. The presence of the κ1-bonded metal triazole causes a significant influence on the electronic properties, structure, and reactivity of this new class of Fischer alkoxycarbenes. For the Ru(II) derivatives, their chemical behavior is considerably influenced by the interaction of the (η5-C5H5)(dppe)RuII-triazole moiety with the empty p-carbene orbital that provokes a noticeable decrease in the electrophilicity of the M═C carbon (manifested by the shielding of the 13C NMR chemical shifts). In turn, in the Co(II) derivatives, the incorporation of the (Me4cyclam)CoII moiety diminishes the aromaticity of the triazole ring and has a marked effect on the energy and distribution of the LUSO orbital, mostly resident on the Co(II) fragment. The almost negligible participation of the carbene moiety in the LUSO makes this position unable to react with nucleophiles. The reactions reported in this work constitute the first examples of [3 + 2] cycloaddition of azides and alkynyl Fischer carbene complexes in solution.

Optimization of an acidic digestion method for the determination of total Pb concentration and its isotope ratios in human blood using ICP-QMS.

Adverse effects of lead (Pb) on human health are observed even at levels below 5 µg/dL, affecting principally the children population and suggesting that there is not a safe exposure level. The determination of Pb isotopic ratios (LIRs) in biological and environmental samples, is an appropriate tool to track and control the exposure sources, because LIRs constitutes the pollutant's isotopic signature and hence can be used to identify sources of Pb emission. This study proposes the optimization of a method in order to significantly reduce the biological samples' matrix interferences, and improves precision and accuracy in the measurements of LIRs. Four total blood digestion methods were evaluated and the results were subjected to statistical methods (ANOVA) determining the combination of HNO3:H2O2 (2:1 v v-1)/g from a sample on a hot plate as the best of them. For the method's validation, detection and quantification limits, linearity range, intermediate precision and recovery were evaluated. The total Pb (PbT) and LIRs were performed by ICP-QMS, defining the optimal value of detector dead time (DT), and correcting mass bias and instrumental drift for this matrix. LIRs based on 206Pb, 207Pb and 208Pb were determined at high precision (%RSD 0.03-0.49%), than those involving 204Pb (%RSD > 0.8). The optimized methodology can be used to identify pollution sources in blood and environmental samples using LIRs (206Pb/207Pb, 207Pb/208Pb, 208Pb/206Pb, etc.) in a trustworthy and simple way, with accurate results.

Silver(I)-Catalyzed Addition of Phenols to Alkyne Cobalt Cluster Stabilized Carbocations.

A smooth catalytic method to use phenols as the nucleophilic partner in the Nicholas reaction has been developed. The method uses either Ag(I) or Au(I) catalysts with AgClO4 or AgBF4 as the most efficient catalysts tested. Neither additional additives nor cocatalysts were required and the formation of the corresponding phenol adducts occurred in excellent yields. The process has the single limitation of the inability of less nucleophilic phenols (4-nitrophenol) to generate the corresponding adducts. Additionally, the reaction is highly diastereoselective. DFT calculations allow a catalytic cycle to be proposed that involves trimetallic intermediates; the rate-determining step of the reaction is hydroxy-group elimination in a cobalt-silver trimetallic intermediate.

Mono- and Bimetallic Alkynyl Metallocenes and Half-Sandwich Complexes: A Simple and Versatile Synthetic Approach.

A general process for the synthesis of alkynyl mono and dimetallic metallocenes and half-sandwich complexes has been developed. This approach uses the addition of lithium derivatives of sandwich or half-sandwich complexes to arylsulfonylacetylenes. The reaction occurs in two steps (lithiation and anti-Michael addition to alkynylsulfone followed by elimination of the ArSO2 moiety) to form the corresponding mono- or bimetallic alkynes in clearly higher yields, simpler experimental procedures, and more environmentally benign conditions than those of the so far reported for the synthesis of this type of products. The electrochemical properties of the newly obtained complexes have also been studied.

Steroid Derived Mesoionic Gold and Silver Mono- and Polymetallic Carbenes.

A two-step synthesis of gold mesoionic carbene complexes containing estrone moieties has been developed. The method uses the methylation of the triazole nucleus, followed by the treatment of the triazolium salt with Ag2O and transmetalation with [AuCl(SMe2)]. Mono-, bi-, tri-, and tetrametallic gold complexes can be obtained depending on the structure of the starting triazolium salts. Tetrametallic gold carbene embedded in a macrocylic stereoidal cavity containing four estrone nuclei has been also prepared. Additionally, the mono- and bimetallic silver carbene complexes containing triazole-steroid ligands have been isolated and characterized. These complexes resulted to be stable and have been characterized by spectroscopic and HRMS techniques. The gold and silver complexes having triazole-steroid ligands are unprecedented in the literature and the method reported here to access to these compounds is easy and efficient. Preliminary results regarding the catalytic activity of some of the gold-carbenes prepared in the insertion of diazoalkanes into alcohols are presented.

The "click" reaction involving metal azides, metal alkynes, or both: an exploration into multimetal structures.

Cu(I) -catalyzed 1,3-cycloaddition of azides and alkynes (CuAAC) is one of the most powerful synthetic methodologies known. However, its use to prepare well-defined multimetallic structures is underdeveloped. Apart from the applications of this reaction to anchor different organometallic reagents to surfaces, polymers, and dendrimers, only isolated examples of CuAAC with metal-η(1) -alkyne and metal-azide complexes to prepare multimetal entities have been reported. This concept sketches the potential of these reactions not only to prepare "a la carte" multimetal 1,2,3-triazole derivatives, but also to discover new and unprecedented reactions.

Platinum-catalysed bisindolylation of allenes: a complementary alternative to gold catalysis.

Pt versus Au: Platinum-catalysed addition of nucleophiles to allenes follows a distinctly different pathway to the process catalysed by gold(I) complexes; the platinum catalyst leads to different products with indoles involving a bisindolylation reaction, whereas gold(I) gives allyl indoles from a single addition (see scheme).

Two versatile and parallel approaches to highly symmetrical open and closed natural product-based structures.

Two parallel approaches for preparing diverse and highly symmetrical homohybrids derived from a series of mono- and diterpenes, steroids, and alkaloids are reported. Both procedures are based on the mono-addition of bis(alkynyl) dilithium reagents to natural products having a carbonyl group to produce the corresponding alkynyl derivatives. The Glaser-Hay Cu-promoted homocoupling of these alkynyl natural product mono-adducts as well as the Huisgen Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction resulted in the synthesis of steroid-, terpene-, and alkaloid-based homohybrid derivatives incorporating diverse spacers to join the natural product scaffolds. Straightforward entries to novel closed highly symmetrical and complex estrone-based macrocyclic and cage architectures by means of the Glaser-Eglinton homocoupling and the CuAAC reaction have been devised.

1,2,3-Triazolium-Derived Mesoionic Carbene Ligands Bearing Chiral Sulfur-Based Moieties: Synthesis, Catalytic Properties, and Their Role in Chirality Transfer.

1,2,3-Triazole-derived mesoionic carbenes (MICs) having a chiral sulfur functional group at the C5 position are easily available through a CuAAC between chiral alkynyl sulfoxides and different azides. The MICs form complexes with several metals (Au, Ag, Ir, Rh, and Ru) that are enantiomerically pure. Moreover, enantiomerically pure MIC sulfinilimines are obtained from the corresponding sulfoxide retaining the chirality. Through this article, the participation of sulfoxide moieties in different catalytic and chirality transfer processes, as well as in discovering mechanistically new processes will be shown. The role of the sulfur chiral moiety in catalytic cycloisomerization and cycloisomerization-dimerization processes using Au-MIC catalysts is dual. The sulfur functional group either stabilizes intermediates in the catalytic cycle, allowing for the reaction to occur or significantly increases the selectivity of the cyclization processes. 1,2,3-Triazole MICs having chiral sulfoxides at C5 are extremely efficient in preparing chiral at the metal complexes by C-H insertion processes. The chiral at the metal half-sandwich complexes, having the enantiopure sulfur chiral group unaltered, experiences different reactions with complete retention of the configuration. Finally, mechanistically new processes, like the desulfinilation of 1,2,3-triazolium salts in Ag-MIC complexes have been uncovered. These still-nascent classes of compounds will offer opportunities for the discovery of novel catalytic applications and to study new mechanistically sound processes.

Desulfinylation of Ag(I) Sulfinyl Mesoionic Carbenes: Preparation of C-Unsubstituted Au(I)-1,2,3-Triazole Carbene Complexes.

New and well-characterized Ag-bis(1,2,3-triazolylidene) complexes having enantiopure (S)-sulfoxides upon sequential treatment with alcohols and Au(I) form separable mixtures of regioisomeric C-unsubstituted Au-1,2,3-triazolylidene complexes. Mechanistic studies and DFT calculations support a desulfinylation process for in situ generated free triazolylidene salts.

Synthesis of alpha-onoceradiene-like terpene dimers by intermolecular metathesis processes.

[reaction: see text] New alpha-onoceradiene analogues having a terpene homodimer skeleton are accessible from Weinreb's amide 2 derived from commercial (R)-(+)-sclareolide using an intermolecular metathesis reaction as the key step to build the linker joining both terpene moieties.

Synthesis of polymetallic macrocyclic terpene-derived hybrids.

Terpene alkyne systems act as templates in the preparation of natural product hybrids and in macrocyclic structures having up to four terpene units and eight Co-atoms, which are built by using the Nicholas reaction.