A Family of Hexacopper Phenylsilsesquioxane/Acetate Complexes: Synthesis, Solvent-Controlled Cage Structures, and Catalytic Activity.

Convenient self-assembly synthesis of copper(II) complexes via double (phenylsilsesquioxane and acetate) ligation allows to isolate a family of impressive sandwich-like cage compounds. An intriguing feature of these complexes is the difference in the structure of a pair of silsesquioxane ligands despite identical (Cu6) nuclearity and number (four) of acetate fragments. Formation of particular combination of silsesquioxane ligands (cyclic/cyclic vs condensed/condensed vs cyclic/condensed) was found to be dependent on the synthesis/crystallization media. A combination of Si4-cyclic and Si6-condensed silsesquioxane ligands is a brand new feature of cage metallasilsesquioxanes. A representative Cu6-complex (4) (with cyclic silsesquioxanes) exhibited high catalytic activity in the oxidation of alkanes and alcohols with peroxides. Maximum yield of the products of cyclohexane oxidation attained 30 %. The compound 4 was also tested as catalyst in the Baeyer-Villiger oxidation of cyclohexanone by m-chloroperoxybenzoic acid: maximum yields of 88 % and 100 % of ϵ-caprolactone were achieved upon conventional heating at 50 °C for 4 h and MW irradiation at 70 or 80 °C during 30 min, respectively. It was also possible to obtain the lactone (up to 16 % yield) directly from the cyclohexane via a tandem oxidation/Baeyer-Villiger oxidation reaction using the same oxidant.

Fe(III)-Based Phenylsilsesquioxane/Acetylacetonate Complexes: Synthesis, Cage-like Structure, and High Catalytic Activity.

Unprecedented iron-based silsesquioxane/acetylacetonate complexes were synthesized. The intriguing cage-like structure of compounds is alkaline metal-dependent: the Fe2Li2 complex includes condensed Si6-silsesquioxane and four acetylacetonate ligands; the Fe4Na4 complex exhibits two cyclic Si4-silsesquioxane and eight acetylacetonate ligands, while the Fe3K3 complex features two cyclic Si3-silsesquioxane and six acetylacetonate ligands. The latter case is the very first observation of small trimeric silsesquioxane ligands in the composition of cage-like metallasilsesquioxanes. The Fe4Na4-based complex exhibits a record high activity in the oxidation of inert alkanes with peroxides (55% yield of oxygenates in cyclohexane oxidation). It also acts as a catalyst in the cycloaddition of CO2 with epoxides, leading to cyclic carbonates in good yields (58-96%).

XXII International Symposium on Homogeneous Catalysis.

This special collection of reviews, minireviews, full papers and communications at Chemistry Europe journals (Chem. Eur. J., ChemCatChem, ChemSusChem, Eur. J. Org. Chem., Eur. J. Inorg. Chem., ChemistryOpen and ChemPhotoChem) is inspired by (and dedicated to) the XXII ISHC, which was held in-presence in Lisbon in 2022.

Control of Selectivity in Homogeneous Catalysis through Noncovalent Interactions.

The regio-, site-, stereo- or chemoselective homogeneous catalytic transformations are extremely important for the growth/success of the current chemical industry. Based on empirical, theoretical or intuitive knowledge, several synthetic strategies, such as ligand design, transient directing group, metal node alternation, metal-ligand cooperation, pore decoration, biomimetic, have already been developed for the selective functionalization of organic substrates. In comparison to the other tactics, the use of noncovalent interactions for the control of selectivity in catalytic transformations of organic compounds may avoid multi-steps, reduce time of synthetic procedure, decrease cost of operation, and increase reactivity of catalyst. In fact, enzymes achieve a high selectivity through noncovalent interactions in biochemical processes in Nature. Guided by the impressive performance of enzymes in biosynthesis and biodegradation reactions, various types of synthetic metal complex or organocatalysts have already been developed, in which the catalyst-substrate noncovalent interactions have a pivotal impact on the distinctive stabilization of the transition states or intermediates, directing selectivity and improving efficiency of homogeneous catalytic reactions. Herein, we highlight several recent and relevant examples of selectivity directing/driving function of noncovalent interactions in the transformation of organic substrate(s) catalyzed by both organocatalysts and metal complex catalysts.

Chalcogen bonding in copper(II)-mediated synthesis.

The chalcogen bond (ChB) is a noncovalent attraction between an electrophilic chalcogen atom and a nucleophilic (Nu) region in the same (intramolecular) or another (intermolecular) molecular entity: R-Ch⋯Nu (Ch = O, S, Se or Te; R = substituents; Nu = nucleophile). ChB is comparable to the hydrogen and halogen bonds both in terms of strengths and directionality. However, in contrast to the monovalent halogen atoms, usually the divalent or tetravalent chalcogen atoms are able to display more than one electrophilic centre (on account of the existence of two or three species bonded to the chalcogen atom), which provides an additional opportunity in the use of this type of noncovalent binding in synthetic operations. In this work, the role of ChB at the secondary coordination sphere of metal complexes through copper(II)-mediated activation of dioxygen or of one nitrile group of a 1,2,5-selenadiazole-3,4-dicarbonitrile ligand to form a carbimidate or an imino-carboxylic acid is demonstrated. DFT calculations allowed evaluation of the strength of the ChBs and proved their relevant structure directing role in the solid state architectures. The effect of metal-coordination on the σ-hole opposite to the coordinated SeO bond has been analysed using molecular electrostatic potential (MEP) surfaces and explains the greater ability of the coordinated selenoxide derivatives to form strong ChBs.

A Family of Cagelike Mn-Silsesquioxane/Bathophenanthroline Complexes: Synthesis, Structure, and Catalytic and Antifungal Activity.

This study reports a novel family of cage manganesesilsesquioxanes prepared via complexation with bathophenanthroline (4,7-diphenyl-1,10-phenanthroline). The resulting Mn4-, Mn6Li2-, and Mn4Na-compounds exhibit several unprecedented cage metallasilsesquioxane structural features, including intriguing self-assembly of silsesquioxane ligands. Complexes were tested in vitro for fungicidal activity against seven classes of phytopathogenic fungi. The representative Mn4Na-complex acts as a catalyst in the cycloaddition of CO2 to epoxides under solvent-free conditions to form cyclic carbonates in good yields.

Cage-like Cu5Cs4-Phenylsilsesquioxanes: Synthesis, Supramolecular Structures, and Catalytic Activity.

A small family of nonanuclear Cu5Cs4-based phenylsilsesquioxanes 1-2 were prepared by a convenient self-assembly approach and characterized by X-ray diffraction studies. The compounds 1 and 2 show some unprecedented structural features such as the presence of a [Ph14Si14O28]14- silsesquioxane ligand and a CuII5CsI4 nuclearity in which the metal cations occupy unusual positions within the cluster. Copper ions are "wrapped" into a silsesquioxane matrix, while cesium ions are located in external positions. This resulted in cesium-involved aggregation of coordination polymer structures. Both compounds 1 and 2 realize specific metallocene (cesium-phenyl) linkage between neighboring cages. Compound 2 is evaluated as a catalyst in the Baeyer-Villiger (B-V) oxidation of cyclohexanone and tandem cyclohexane oxidation/B-V oxidation of cyclohexanone with m-chloroperoxybenzoic acid (mCPBA) as an oxidant, in an aqueous acetonitrile medium, and HNO3 as the promoter. A quantitative yield of ε-caprolactone was achieved under conventional heating at 50 °C for 4 h or MW irradiation for 30 min (for cyclohexanone as substrate); 17 and 19% yields of lactone upon MW irradiation at 80 °C for 30 min and heating at 50 °C for 4 h, respectively (for cyclohexane as a substrate), were achieved. Complex 2 was evaluated as a catalyst for the oxidation of alkanes to alkyl hydroperoxides and alcohols to ketones with peroxides at 60 °C in acetonitrile. The maximum yield of cyclohexane oxidation products was 30%. Complex 2 exhibits high activity in the oxidation of alcohols.

Noncovalent Interactions at Lanthanide Complexes.

Lanthanide complexes have attracted a widespread attention due to their structural diversity, as well as multifunctional and tunable properties. The development of lanthanide based functional materials has often relied on the design of the secondary coordination sphere of the corresponding lanthanide complexes. For instance, usually simple lanthanide salts (solvento complexes) do not catalyze effectively organic reactions or provide low yield of the expected product, whereas the presence of a suitable organic ligand with a noncovalent bond donor or acceptor centre (secondary coordination sphere) modifies the symmetry around the metal centre in lanthanide complexes which then successfully can act as catalysts in both homogenous and heterogenous catalysis. In this minireview, we discuss several relevant examples, based on X-ray crystal structure analyses, in which the hydrogen, halogen, chalcogen, pnictogen, tetrel and rare-earth bonds, as well as cation-π, anion-π, lone pair-π, π-π and pancake interactions, are used as a synthon in the decoration of the secondary coordination sphere of lanthanide complexes.

Resonance Assisted Chalcogen Bonding as a New Synthon in the Design of Dyes.

Intramolecular chalcogen bonding in arylhydrazones of sulfamethizole is strengthened by conjugation in the π-system of a noncovalent five-membered ring. The S⋅⋅⋅O distance in the sulfamethizole moiety of these compounds ranges from 2.698(3) to 2.806(15) Å, which indicates its strong dependence on the attached arylhydrazone fragments. Information on the nature of the intramolecular chalcogen bond was afforded by DFT calculations.

In vitro characterization of arylhydrazones of active methylene derivatives.

Arylhydrazones of active methylene compounds (AHAMCs) are potent chemotherapy agents for the cancer treatment. AHAMCs enhance the apoptotic cell death and antiproliferation properties in cancer cells. In this study, a series of AHAMCs, 13 compounds, was assayed for cytotoxicity, apoptosis, externalization of phosphatidylserine, heterogeneity and cellular calcium level changes. The in vitro cytotoxicity study against HEK293T cells suggests that AHAMCs have significant cytotoxic effect over the concentrations. Top 5 compounds, 5-(2-(2-hydroxyphenyl) hydrazono)pyrimidine-2,4,6(1H,3H,5H)-trione (5), 4-hydroxy-5-(2-(2,4,6-trioxo-tetrahydro-pyrimidin-5(6H) ylidene)hydrazinyl)benzene-1,3-disulfonic acid (6), 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxybenzenesulfonic acid (8), 5-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-4-hydroxybenzene-1,3-disulfonic acid (9) and 2-(2-sulfophenylhydrazo)malononitrile (10) were chosen for the pharmacodynamics study. Among these, compound 5 exhibited the better cytotoxic effect with the IC50 of 50.86 ±â€¯2.5 mM. DNA cleavage study revealed that 5 induces cell death through apoptosis and shows more effects after 24 and/or 48 h. Independent validation of apoptosis by following the externalization of phosphatidylserine using Annexin-V is also in agreement with the potential activity of 5. Single cell image analysis of Annexin-V bound cells confirms the presence of mixture of early, mid and late apoptotic cells in the population of the cells treated with 5 and a decreased trend in cell-to-cell variation over the phase was also identified. Additionally, intracellular calcium level measurements identified the Ca2+ up-regulation in compound treated cells. A brief inspection of the effect of the compound 5 against multiple human brain astrocytoma cells showed a better cell growth inhibitory effect at micro molar level. These systematic studies provide insights in the development of novel AHAMACs compounds as potential cell growth inhibitors for cancer treatment.

Resonance-Assisted Hydrogen Bonding as a Driving Force in Synthesis and a Synthon in the Design of Materials.

Resonance-assisted hydrogen bonding (RAHB), a concept introduced by Gilli and co-workers in 1989, concerns a kind of intramolecular H-bonding strengthened by a conjugated π-system, usually in 6-, 8-, or 10-membered rings. This Review highlights the involvement of RAHB as a driving force in the synthesis of organic, coordination, and organometallic compounds, as a handy tool in the activation of covalent bonds, and in starting moieties for synthetic transformations. The unique roles of RAHB in molecular recognition and switches, E/Z isomeric resolution, racemization and epimerization of amino acids and chiral amino alcohols, solvatochromism, liquid-crystalline compounds, and in synthons for crystal engineering and polymer materials are also discussed. The Review can provide practical guidance for synthetic chemists that are interested in exploring and further developing RAHB-assisted synthesis and design of materials.

Cooperative metal-ligand assisted E/Z isomerization and cyano activation at Cu(II) and Co(II) complexes of arylhydrazones of active methylene nitriles.

New (E/Z)-2-(2-(1-cyano-2-methoxy-2-oxoethylidene)hydrazinyl)benzoic acid (H2L(4)) and known sodium 2-(2-(dicyanomethylene)hydrazinyl)benzenesulfonate (NaHL(1)), 2-(2-(dicyano-methylene)hydrazinyl)benzoic acid (H2L(2)), and sodium (E/Z)-2-(2-(1-cyano-2-methoxy-2-oxoethylidene)hydrazinyl)benzenesulfonate (NaHL(3)) were used in the template synthesis of a series of Cu(II) and Co(II) complexes [Cu(H2O)2L(1a)]·H2O (1), [Cu(H2O)(3-pyon)L(1b)]·H2O (2), [Cu(H2O)(4-pyon)L(1b)] (3), [Co(H2O)((CH3)2NCHO)(µ-L(2a))]2·(CH3)2NCHO (4), [Cu3(µ3-OH)(NO3)(CH3OH)(µ2-X)3(µ2-HL(3))] (5), [Cu(H2O)(py)L(3)]·H2O (6), [Cu(H2O)2(µ-L(4))]6·6H2O (7), [Cu(2-cnpy(b))2(L(1b))2]·2H2O (8), [Cu(2-cnpy(a))2(L(1a))2]·2H2O (9), and [Cu(H2O)(4-cnpy)(L(1a))2] (10), where 3-pyon = 1-(pyridin-3-yl)ethanone, 4-pyon = 1-(pyridin-4-yl)ethanone, py = pyridine, HX = syn-2-pyridinealdoxime, 4-cnpy = 4-cyanopyridine; 2-cnpy(a), 2-cnpy(b), L(1a), L(1b), L(2a) are the ligands derived from nucleophilic attack of methanol (a) or water (b) on a cyano group of 2-cyanopyridine (2-cnpy), L(1) or L(2), respectively, giving the corresponding iminoesters (2-cnpy(a), L(1a) or L(2a)) or carboxamides (2-cnpy(b) or L(1b)). An auxiliary ligand, namely syn-2-pyridinealdoxime or pyridine, acting cooperatively with the metal ion (Cu(II) in this case), induced an E/Z isomerization of the H2L(4) ligand; the E- and Z-isomers were isolated separately and fully characterized (compounds 9 and 10, respectively). A one-pot activation of nitrile groups in different molecules was achieved in the syntheses of 8 and 9. Complexes 1-10 are catalyst precursors for the solvent-free microwave (MW)-assisted selective oxidation of secondary alcohols to the corresponding ketones, with typical yields in the 29-99% range (TOFs up to 4.94 × 10(3) h(-1)) after 30 min of MW irradiation.

Design, synthesis and anticancer evaluation of novel arylhydrazones of active methylene compounds.

Nerve growth factor (NGF) and its receptor, tropomyosin kinase receptor kinase type A (TrkA) is emerging as an important target for Glioblastoma (GBM) treatment. TrkA is the cancer biomarker majorly involved in tumor invasion and migration into nearby normal tissue. However, currently, available Trk inhibitors exhibit many adverse effects in cancer patients, thus demanding a novel class of ligands to regulate Trk signaling. Here, we exploited the role of TrkA (NTRK1) expression from the 651 datasets of brain tumors. RNA sequence analysis identified overexpression of NTRK1 in GBM, recurrent GBM as well in Oligoastrocytoma patients. Also, TrkA expression tends to increase over the higher grades of GBM. TrkA protein targeting hydrazone derivatives, R48, R142, and R234, were designed and their mode of interaction was studied using molecular docking and dynamic simulation studies. Ligands' stability and binding assessment reveals R48, 2 2-(2-(2-hydroxy-4-nitrophenyl) hydrazineylidene)-1-phenylbutane-1,3-dione, as a potent ligand that interacts well with TrkA's hydrophobic residues, Ile, Phe, Leu, Ala, and Val. R48- TrkA exhibits stable binding potentials with an average RMSD value <0.8 nm. R48 obeyed Lipinski's rule of five and possessed the best oral bioavailability, suggesting R48 as a potential compound with drug-likeness properties. In-vitro analysis also revealed that R48 exhibited a higher cytotoxicity effect for U87 GBM cells than TMZ with the IC50 value of 68.99 µM. It showed the lowest percentage of cytotoxicity to the non-cancerous TrkA expressing MEF cells. However, further SiRNA analysis validates the non-specific binding of R48, necessitating structural alteration for the development of R48-based TrkA inhibitor for GBM therapeutics.

Template syntheses of copper(II) complexes from arylhydrazones of malononitrile and their catalytic activity towards alcohol oxidations and the nitroaldol reaction: hydrogen bond-assisted ligand liberation and E/Z isomerisation.

A one-pot template condensation of 2-(2-(dicyanomethylene)hydrazinyl)benzenesulfonic acid (H(2)L(1), 1) or 2-(2-(dicyanomethylene)hydrazinyl)benzoic acid (H(2)L(2), 2) with methanol (a), ethylenediamine (b), ethanol (c) or water (d) on copper(II), led to a variety of metal complexes, that is, mononuclear [Cu(H(2)O)(2)(κO(1),κN(2)L(1a)] (3) and [Cu(H(2)O)(κO(1),κN(3)L(1b))] (4), tetranuclear [Cu(4)(1κO(1),κN(2):2κO(1)L(2a))(3)-(1κO(1), κN(2):2κO(2)L(2a))] (5), [Cu(2)(H(2)O)(1κO(1), κN(2):2κO(1)L(2c))-(1κO(1),1κN(2):2κO(1),2 κN(1)- L(2c))](2) (6) and [Cu(2)(H(2)O)(2)(κO(1),κN(2)- L(1dd))-(1κO(1),κN(2):2κO(1)L(1dd))(µ-H(2)O)](2·) 2H(2)O (7·2H(2)O), as well as polymer- ic [Cu(H(2)O)(κO(1),1κN(2):2κN(1)L(1c))](n) (8) and [Cu(NH(2)C(2)H(5))(κO(1),1κN(2):2κN(1)L(2a))](n) (9). The ligands 2-SO(3)H-C(6)H(4)-(NH)N=C{(CN)[C(NH(2))-(=NCH(2)CH(2)NH(2))]} (H(2)L(1b), 10), 2-CO(2)H-C(6)H(4)-(NH)N={C(CN)[C(OCH(3))-(=NH)]} (H(2)L(2a), 11) and 2-SO(3)H-C(6)H(4)-(NH)N=C{C(=O)-(NH(2))}(2) (H(2)L(1dd), 12) were easily liberated upon respective treatment of 4, 5 and 7 with HCl, whereas the formation of cyclic zwitterionic amidine 2-(SO(3)(−))-C(6)H(4)-N=NC(-C=(NH(+))CH(2)CH(2)NH)(=CNHCH(2)CH(2)NH) (13) was observed when 1 was treated with ethylenediamine. The hydrogen bond-induced E/Z isomerization of the (HL(1d))(−) ligand occurs upon conversion of [{Na(H(2)O)(2)(µ-H(2)O)(2)}(HL(1d))](n) (14) to [Cu(H(2)O)(6)][HL(1d)](2)·2H(2)O (15) and [{CuNa(H(2)O)-(κN(1),1κO(2):2κO(1)L(1d))(2)}K(0.5)(µ-O)(2)]n·H(2)O (16). The synthesized complexes 3­9 are catalyst precursors for both the selective oxidation of primary and secondary alcohols (to the corresponding carbonyl compounds) and the following diastereoselective nitroaldol (Henry) reaction, with typical yields of 80­99%.

Iron(III) Arylhydrazone Complexes Immobilized on Amine-Functionalized Mesoporous Silica: Catalysts for the Valorization of Biomass-Derived Furfuryl Alcohol.

The aquasoluble FeIII complexes [Fe(H2 O)3 (L1 )] ⋅ 4H2 O (Fe1) and [Fe(H2 O)3 (L2 )] ⋅ 3H2 O (Fe2), bearing the basic forms of 5-chloro-3-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)hydrazinyl)-2-hydroxy-benzenesulfonic acid (H3 L1 ) and 3-(2-(2,4-dioxopentan-3-ylidene)hydrazinyl)-2-hydroxy-5-nitrobenzenesulfonic acid (H3 L2 ), were incorporated for the first time into amine-functionalized SBA-15 support via an impregnation method. The successful preparation of the composites was confirmed by Fourier-Transform Infrared spectroscopy (FT-IR), powder X-ray diffraction (XRD), scanning electron microscope (SEM/EDS), transmission electron microscopy (TEM), elemental analysis, and nitrogen adsorption-desorption isotherms. The resulting Fe1@aptesSBA-15 and Fe2@aptesSBA-15 composites were tested as the first SBA-15-based heterogeneous catalysts for the conversion of furfuryl alcohol under mild reaction conditions (80 to 100 °C) and with an environmentally friendly oxidant (TBHP, 70 % aq. sol. with 1 : 1 oxidant/substrate molar ratio). The influence of various factors, such as reaction time, amounts of oxidant and catalyst, was investigated. The reaction time can be fairly reduced by adopting a microwave-assisted method allowing it to reach complete conversion after 0.25 h, in the absence of any added solvent or additive. Under these conditions, a vigorous furfuryl alcohol polymerization process occurred, with furfural as a by-product. Recycling studies were carried out for Fe2@aptesSBA-15 and after four consecutive runs, the overall conversion of furfuryl alcohol remained high (≥99 %), without an appreciable change in the obtained yield.

Halogen Bonding in the Decoration of Secondary Coordination Sphere of Zinc(II) and Cadmium(II) Complexes: Catalytic Application in Cycloaddition Reaction of CO2 with Epoxides.

Three new zinc(II) complexes [Zn(H2L3)2(H2O)3] (Zn2), [Zn(H3L2a)(H2O)3]n (Zn3) (H3L2a = 2,4-diiodo-5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl)isophthalate) and [Zn(HL4)(DMF)(H2O)]n (Zn4) were synthesized by the reaction of Zn(II) salts with 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl) isophthalic acid (H3L3), 2,4,6-triiodo-5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene)hydrazineyl) isophthalic acid (H5L2) (in the presence of NH2OH·HCl) and 5-(2-(2,4-dioxopentan-3-ylidene)hydrazineyl)-2,4,6-triiodoisophthalic acid (H3L4), respectively. According to the X-ray structural analysis, the intramolecular resonance-assisted hydrogen bond ring remains intact, with N···O distances of 2.562(5) and 2.573(5) Å in Zn2, 2.603(6) Å in Zn3, and 2.563(8) Å in Zn4. In the crystal packing of Zn3, the cooperation of I···O and I···I types of halogen bonds between tectons leads to a one-dimensional supramolecular polymer, while I···O interactions aggregate 1D chains of coordination polymer Zn4. These new complexes (Zn2, Zn3, and Zn4) and known [Zn(H3L1)(H2O)2]n (Zn1) (H3L1 = 5-(2-(2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene) hydrazineyl)isophthalate), {[Zn(H3L1)(H2O)3]·3H2O}n (Zn5), [Cd(H3L1)(H2O)2]n (Cd1), {[Cd(HL3)(H2O)2(DMF)]·H2O}n (Cd2), [Cd(H3L3)]n (Cd-3), {[Cd2(µ-H2O)2(µ-H2L4)2(H2L4)2]·2H2O}n (Cd4), and {[Cd(H3L1)(H2O)3]·4H2O}n (Cd5) were tested as catalysts in the cycloaddition reaction of CO2 with epoxides in the presence of tetrabutylammonium halides as the cocatalyst. The halogen-bonded catalyst Zn4 is the most efficient one in the presence of tetrabutylammonium bromide by affording a high yield (85-99%) of cyclic carbonates under solvent-free conditions after 48 h at 40 bar and 80 °C.