Synthesis, characterization, and biological activity of cationic ruthenium-arene complexes with sulfur ligands.

Five cationic ruthenium-arene complexes with the generic formula [Ru(SAc)(S2C·NHC)(p-cymene)](PF6) (5a-e) were prepared in almost quantitative yields using a straightforward one-pot, two-step experimental procedure starting from [RuCl2(p-cymene)]2, an imidazol(in)ium-2-dithiocarboxylate (NHC·CS2) zwitterion, KSAc, and KPF6. These half-sandwich compounds were fully characterized by various analytical techniques and the molecular structures of two of them were solved by X-ray diffraction analysis, which revealed the existence of an intramolecular chalcogen bond between the oxygen atom of the thioacetate ligand and a proximal sulfur atom of the dithiocarboxylate unit. DFT calculations showed that the C=S…O charge transfer amounted to 2.4 kcal mol-1. The dissolution of [Ru(SAc)(S2C·IMes)(p-cymene)](PF6) (5a) in moist DMSO-d6 at room temperature did not cause the dissociation of its sulfur ligands. Instead, p-cymene was slowly released to afford the 12-electron [Ru(SAc)(S2C·IMes)]+ cation that could be detected by mass spectrometry. Monitoring the solvolysis process by 1H NMR spectroscopy showed that more than 22 days were needed to fully decompose the starting ruthenium-arene complex. Compounds 5a-e exhibited a high antiproliferative activity against human glioma Hs683 and human lung carcinoma A549 cancer cells. In particular, the IMes derivative (5a) was the most potent compound of the series, achieving toxicities similar to those displayed by marketed platinum drugs.

Nickel(II)-Catalyzed Formal [3+2] Cycloadditions between Indoles and Donor-Acceptor Cyclopropanes.

This article describes the development of a nickel-catalyzed regio- and diastereoselective formal [3+2] cycloaddition between N-substituted indoles and donor-acceptor cyclopropanes to synthesize cyclopenta[b]indoles. Optimized reaction conditions provide the desired nitrogen-containing cycloadducts in up to 93% yield and dr 8.6:1 with complete regioselectivity. The substrate scope showed high tolerance to various substituted indoles and cyclopropanes, resulting in the synthesis of six new cyclopenta[b]indoles and the isolation of five derivatives previously reported in the literature. In addition, a mechanistic proposal for the reaction was studied through online reaction monitoring by ESI-MS, allowing for the identification of the reactive intermediates in the Ni(II) catalyzed process. X-ray crystallography confirmed the structure and relative endo stereochemistry of the products. This method enables the fast and efficient construction of fused indolines from readily accessible starting materials.

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes.

The synthesis of zwitterionic dithiocarboxylate adducts was achieved by deprotonating various aldiminium or 1,2,3-triazolium salts with a strong base, followed by the nucleophilic addition of the in situ-generated cyclic (alkyl)(amino) or mesoionic carbenes (CAACs or MICs) onto carbon disulfide. Nine novel compounds were isolated and fully characterized by 1H and 13C NMR, FTIR, and HRMS techniques. Moreover, the molecular structures of two CAAC·CS2 and two MIC·CS2 betaines were determined by X-ray diffraction analysis. The analytical data recorded for all these adducts were compared with those reported previously for related NHC·CS2 betaines derived from imidazolinium or (benz)imidazolium salts. Due to the absence of electronic communication between the CS2 unit and the orthogonal heterocycle, all the CAAC·CS2, MIC·CS2, and NHC·CS2 zwitterions displayed similar electronic properties and featured the same bite angle. Yet, their steric properties are liable to ample modifications by varying the exact nature of their cationic heterocycle and its substituents.

Two Synthetic Approaches to Coinage Metal(I) Mesocates: Electrochemical versus Chemical Synthesis.

We report two different approaches to isolate neutral and cationic mesocate-type metallosupramolecular architectures derived from coinage monovalent ions. For this purpose, we use a thiocarbohydrazone ligand, H2L (1), conveniently tuned with bulky phosphine groups to stabilize the MI ions and prevent ligand crossing to achieve the selective formation of mesocates. The neutral complexes [Cu2(HL)2] (2), [Ag2(HL)2] (3), and [Au2(HL)2] (4) were prepared by an electrochemical method, while the cationic complexes [Cu2(H2L)2](PF6)2 (5), [Cu2(H2L)2](BF4)2 (6), [Ag2(H2L)2](PF6)2 (7), [Ag4(HL)2](NO3)2 (8), and [Au2(H2L)2]Cl2 (9) were obtained by using a metal salt as the precursor. All of the complexes are neutral or cationic dinuclear mesocates, except the silver nitrate derivative, which exhibits a tetranuclear cluster mesocate architecture. The crystal structures of the neutral and cationic copper(I), silver(I), and gold(I) complexes allow us to analyze the influence of synthetic methodology or the counterion role on both the micro- and macrostructures of the mesocates.

Synthesis, Characterization, and Biological Activity of Water-Soluble, Dual Anionic and Cationic Ruthenium-Arene Complexes Bearing Imidazol(in)ium-2-dithiocarboxylate Ligands.

An efficient synthetic protocol was devised for the preparation of five cationic ruthenium-arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands from the [RuCl2(p-cymene)]2 dimer and 2 equiv of an NHC·CS2 zwitterion. The reactions proceeded cleanly and swiftly in dichloromethane at room temperature to afford the expected [RuCl(p-cymene)(S2C·NHC)]Cl products in quantitative yields. When the [RuCl2(p-cymene)]2 dimer was reacted with only 1 equiv of a dithiolate betaine under the same experimental conditions, a set of five bimetallic compounds with the generic formula [RuCl(p-cymene)(S2C·NHC)][RuCl3(p-cymene)] was obtained in quantitative yields. These novel, dual anionic and cationic ruthenium-arene complexes were fully characterized by various analytical techniques. NMR titrations showed that the chelation of the dithiocarboxylate ligands to afford [RuCl(p-cymene)(S2C·NHC)]+ cations was quantitative and irreversible. Conversely, the formation of the [RuCl3(p-cymene)]- anion was limited by an equilibrium, and this species readily dissociated into Cl- anions and the [RuCl2(p-cymene)]2 dimer. The position of the equilibrium was strongly influenced by the nature of the solvent and was rather insensitive to the temperature. Two monometallic and two bimetallic complexes cocrystallized with water, and their molecular structures were solved by X-ray diffraction analysis. Crystallography revealed the existence of strong interactions between the azolium ring protons of the cationic complexes and neighboring donor groups from the anions or the solvent. The various compounds under investigation were highly soluble in water. They were all strongly cytotoxic against K562 cancer cells. Furthermore, with a selectivity index of 32.1, the [RuCl(p-cymene)(S2C·SIDip)]Cl complex remarkably targeted the erythroleukemic cells vs mouse splenocytes.

Genomic Characterization of a Rare, de Novo Unbalanced ins(3;1)(p25.3;q21.3q23.3) in a Female Child with Multiple Congenital Anomalies.

"Simple" 1-way interchromosomal insertions involving an interstitial 1q segment are rare, and therefore, their characterization at the base pair level remains understudied. Here, we describe the genomic characterization of a previously unreported de novo interchromosomal insertion (3;1) entailing an about 12-Mb pure gain of 1q21.3q23.3 that causes typical (microcephaly, developmental delay, and facial dysmorphism) and atypical (interauricular communication, small feet with bilateral deep plantar creases, syndactyly of II-IV toes, and mild pachyonychia of all toes) clinical manifestations associated with this region. Based on our analyses, we hypothesize that the duplication of a subset of morbid genes (including LMNA, USF1, VANGL2, LOR, and POGZ) could account for most clinical findings in our patient. Furthermore, the apparent disruption of a promoter region (between CPNE9 and BRPF1) and a topologically associated domain also suggests likely pathogenic reconfiguration/position effects to contribute to the patient's phenotype. In addition to further expanding the clinical spectrum of proximal 1q duplications and evidencing the phenotypical heterogeneity among similar carriers, our genomic findings and observations suggest that randomness - rather than lethality issues - may account for the paucity of "simple" interchromosomal insertions involving the 1q21.3q23.3 region as genomic donor and distal 3p25.3 as receptor. Moreover, the microhomology sequence found at the insertion breakpoint is consistent with a simple nonhomologous end-joining mechanism, in contrast to a chromothripsis-like event, which has previously been seen in other nonrecurrent insertions. Taken together, the data gathered in this study allowed us to inform this family about the low recurrence risk but not to predict the reproductive prognosis for hypothetical carriers. We highlight that genomic-level assessment is a powerful tool that allows the visualization of the full landscape of sporadic chromosomal injuries and can be used to improve genetic counseling.

Selective Metal-Assisted Assembly of Mesocates or Helicates with Tristhiosemicarbazone Ligands.

The effect of the ligand and/or metal-related factors on the formation of tristhiosemicarbazone metallosupramolecular complexes has been studied in this work. The crystal structures of zinc(II) and lead(II) tristhiosemicarbazone mesocates and a hydrolyzed cadmium(II) helicate let us better rationalize some factors involved in the selective formation of helicates or mesocates.

Effect of the Metal Ion on the Enantioselectivity and Linkage Isomerization of Thiosemicarbazone Helicates.

The effect of the metal ion and ligand design on the enantioselectivity and linkage isomerization of neutral cobalt and zinc bisthiosemicarbazone metallohelicates has been investigated in this work. The electrochemical synthesis has afforded the enantioselective formation of chirally pure cobalt helicates, and the ΛΛ isomer of a single enantiomer has been crystallized as only product for the cobalt methyl-substituted thiosemicarbazone helicate. Interestingly linkage isomers have been formed from zinc ethyl-substituted thiosemicarbazone helicate enantiomers for the first time. The co-existence of these isomers has been evaluated from the point of view of both experimental results and computational calculations.

"The Golden Method": Electrochemical Synthesis Is an Efficient Route to Gold Complexes.

Gold compounds to be obtained by the direct electrochemical oxidation of a noble metal are reported. This achievement provides an alternative procedure to obtaining neutral gold compounds with potential medical or catalytic applications.

Enantioselective synthesis of α-benzylated lanthionines and related tripeptides for biological incorporation into E. coli peptidoglycan.

The synthesis of modified tripeptides (S)-Ala-γ-(R)-Glu-X, where X = (R,S) or (R,R) diastereomers of α-benzyl or α-(4-azidobenzyl)lanthionine, was carried out. The chemical strategy involved the enantioselective alkylation of a 4-MeO-phenyloxazoline. The reductive opening of the alkylated oxazolines, followed by cyclization and oxidation, led to four PMB-protected sulfamidates. Subsequent PMB removal, Boc protection and regioselective opening with cysteine methyl ester led to protected lanthionines. These compounds were further converted in a one pot process to the corresponding protected tripeptides. After ester and Boc deprotection, the four tripeptides were evaluated as potential analogues of the natural tripeptide (S)-Ala-γ-(R)-Glu-meso-A2pm. These compounds were evaluated for introduction, by means of the biosynthetic recycling pathway, into the peptidoglycan of Escherichia coli. A successful in vitro biosynthesis of UDP-MurNAc-tripeptides from the tripeptides containing α-benzyl lanthionine was achieved using purified murein peptide ligase (Mpl). Bioincorporation into E. coli W7 did not occur under different tested conditions probably due to the bulky benzyl group at the Cα carbon of the C-terminal amino acid.

Homoleptic ruthenium(II) complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands: synthesis, characterization, and redox properties.

Five cationic ruthenium(II) chelates with the generic formula [Ru(S2C·NHC)3](PF6)2 were readily obtained upon cleavage of the [RuCl2(p-cymene)]2 dimer with representative imidazol(in)ium-2-dithiocarboxylate zwitterions (NHC·CS2) in the presence of KPF6. The homoleptic complexes were fully characterized by various analytical techniques and the molecular structure of one of them was determined by single-crystal X-ray diffraction analysis. As expected, it featured an octahedral RuS6 core surrounded by three imidazol(in)ium rings and their nitrogen substituents. The robustness of the Ru-S bonds combined with the chelate effect of the κ2-S,S'-dithiocarboxylate units and the steric protection imparted by bulky 1,3-diarylimidazol(in)ium groups most likely accounted for the outstanding stability of these species in solution. Cyclic voltammetry showed that the five homoleptic complexes featured characteristic waves for a monoelectronic redox process corresponding to the RuIII/RuII couple with E1/2 values ranging between 0.97 and 1.27 V vs. Ag/AgCl. This half-wave potential was clearly dependent on the nature of their ancillary ligands as the evolution of the Ep,ox values roughly paralleled the basicity sequence of the NHCs used to prepare them, in line with the trends observed when monitoring the chemical shifts of the CS2- unit on 13C NMR spectroscopy and the CS2- asymmetric stretching vibration wavenumbers on IR spectroscopy.

Nickel, copper, and zinc dinuclear helicates: how do bulky groups influence their architecture?

The ligand design factors that may influence the isolation of metallosupramolecular helicates or mesocates still deserve to be investigated. In this sense, dinuclear nickel(II), copper(II) and zinc(II) compounds were obtained by electrochemical synthesis using a family of five Schiff base ligands, H2Ln (n = 1-5), derived from bisphenylmethane and functionalized with bulky tert-butyl groups in the periphery and ethyl groups in the spacer. Six of the new complexes were characterized by X-ray crystallography, thus demonstrating that the helicate structure is predominant in the solid state. 1H NMR studies were performed for the zinc complexes to analyze if the helical architecture of the metal complexes is retained in solution. These studies reveal that the presence of a tert-butyl group in the ortho position with respect to the OH group is an essential factor identified for the existence of a helicate conformation in solution.

First examples of metal-organic frameworks with the novel 3,3'-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic spacer. Luminescence and adsorption properties.

We report the synthesis of a novel ligand, 3,3'-(1,2,4,5-tetrazine-3,6-diyl)dibenzoic acid (1). In this fragment, we have introduced two carboxylate groups with the aim of using this ligand as a linker to construct three-dimensional metal-organic frameworks (MOFs). We have been successful in the formation of zinc (2) and lanthanum (3) MOFs. The zinc compound is a two-dimensional structure, while the lanthanum material is a three-dimensional MOF with interesting channels. We include the luminescence and adsorption studies of these materials. Moreover, we have evaluated the in vitro toxicity of this novel ligand, concluding that it can be considered negligible.

The facile alkylation and iodination of imidazol(in)ium salts in the presence of cesium carbonate.

The alkylation or iodination of imidazol(in)ium salts takes place readily in the presence of Cs2CO3. The procedure is very easy to implement and provides facile and straightforward access to a wealth of C2-substituted azolium salts. Furthermore, a C2α alkylation is also feasible, which extends the chemistry of NHCs and weak bases to their NHO analogues.

Application of Machine Learning to Characterize the Permeate Quality in Pilot-Scale Vacuum-Assisted Air Gap Membrane Distillation Operation.

Membrane distillation (MD) is a thermal desalination technique proposed for the valorization of residual brines that other operations such as reverse osmosis cannot treat. Previous studies have shown that vacuum-assisted air gap (V-AGMD) operation in commercial multi-envelope modules improves the performance of MD noticeably. However, the permeate quality at pilot scale has not been thoroughly characterized so far. The aim of this study is, therefore, to assess and model the effect of the main operating conditions (feed flow rate, inlet temperatures, and feed salinity) on the permeate quality. Results from different steady-state experiments allowed to estimate descriptive metrics such as the salt rejection factor (SRF) and the membrane leak ratio (MLR). Given their non-linear behavior, these metrics were subsequently modeled using artificial neural networks (ANN) to estimate the permeate quality in the whole scope of operating conditions. Acceptable SRF results with MLR values lower than 0.2% confirmed the validity of MD as an operation for the treatment of concentrated brines, although the salinity of the resulting permeate does not comply in all cases with that permitted for human consumption.

Ligand influence in electrocatalytic properties of Cu(II) triazole complexes for hydrogen peroxide detection in aqueous media.

In this work, electrocatalytic changes of Cu(II) triazole complexes (Cu(L)2) resulting from inductive effects were evaluated to fabricate a sensor for hydrogen peroxide (H2O2) determination. Three copper(II) complexes with electronically differentiated ligands were synthesized by slow diffusion method and characterized by X-ray crystallography, Fourier transformed infrared (FTIR), UV-Vis, scanning electron microscopy (SEM) and voltammetry cyclic (CV). Cu(LOMe)2/GC, Cu(LBr)2/GC and Cu(LNO2)2/GC sensors were then prepared. Under optimal conditions (pH = 11), the optimal sensor presented a response at -0.5 V, good linear range of 1-32 µM, reproducibility (1.7%), repeatability (1.2%), LOD of 0.0246 µM (S/N = 5), LOQ of 0.0747 µM (S/N = 5) and selectivity. Additionally, Cu(LNO2)2/GC sensor has been successfully applied in commercial substances, such as mouthwash, milk and tea.

A chemosensor for dihydrogenphosphate based on an oxoazamacrocycle possessing three thiourea arms.

We report a new H-bond macrocyclic chromogenic chemosensor in organic media, H(3)L, which displayed drastic changes in its UV-vis spectra revealing selectivity for dihydrogenphosphate over other inorganic anions, such as acetate or fluoride. The X-ray crystal structures of the [H(4)L···NO(3)]·(CH(3)CN)(4) and [H(4)L···CF(3)CO(2)]·(CH(3)CN)(2) salt complexes are also reported.

Cl-OH ion-exchanging process in chlorapatite (Ca5(PO4)3Cl(x)(OH)(1-x))--a deep insight.

We have synthesized large chlorapatite [ClAp, Ca(5)(PO(4))(3)Cl(x)(OH)(1-x), where x = 1] single crystals using the molten salt method. We have corroborated that the hexagonal symmetry P6(3)/m describes the crystal structure best, even though the crystals are synthetic and stoichiometric. Moreover, we have performed several thermal treatments on these ClAp crystals, generating new single crystals in the apatite system [Ca(5)(PO(4))(3)Cl(x)(OH)(1-x), where x ≤ 1], where the chloride anions (Cl(-)) were systematically substituted by hydroxyl anions (OH(-)). These new single crystals were methodically characterized by powder and single-crystal X-ray diffraction (SXRD), scanning electron microscopy (SEM), Fourier transform-IR spectroscopy (FT-IR), and energy-dispersive X-ray spectroscopy (EDS). We have discovered a previously unreported OH(-) inclusion site substituting the Cl(-) anion during the ion-exchanging process. Finally, we evaluated the atomic rearrangements of the other species involved in the structure. These movements are associated with ionic exchange, which can be justified from an energetic point of view. We also found a novel phase transformation at high temperature. When the crystals are heated over 1753 K the apatite system evolves to a less ordered monoclinic structure, in which the complete loss of the species in the anionic channel (Cl(-), OH(-)) has been confirmed.

A solar energy desalination analysis tool, sedat, with data and models for selecting technologies and regions.

There is interest for desalination technologies powered by solar energy as arid areas are typically bestowed with good solar potential. In response to a US DOE call for solar desalination analysis tools, we developed an open-source solar energy desalination analysis tool, sedat, for techno-economical evaluation of desalination technologies and selection of regions with the highest potential for using solar energy to power desalination plants. It is expected that this software will simplify the planning, design, and valuation of solar desalination systems in the U.S. and worldwide. Sedat uses Dash for integrating various layers of large volumes of GIS data with Python-based models of solar energy generation and desalination technologies. It derives time-series of energy generation and water production, with details of plant performance and suggestions for improving the solar-desalination coupling. This paper summarizes the various phases of the tool's development, presents example results showing the potential, under multiple objectives, of solar desalination in parts of the U.S. southwest, and discusses method details that would be useful for future model development.

Hydrolysis of a carbamate triggered by coordination of metal ions.

The mechanism of carbamate activation promoted by different metal ions has been explored in this work. The reaction of the carbamate ligand H2L with chloride metal salts (M = Ni, Cu, Zn, Cd) leads to the coordination of the metal ions to the ligand, causing hydrolysis of the systems. This self-immolation process results in mononuclear dihydrazone complexes, carbon dioxide and the release of alcohol species from the pendant groups of the carbamate ligand. The conditions under which this process occurs have been studied in detail.