The Synthesis and Biological Activity of Organotin Complexes with Thio-Schiff Bases Bearing Phenol Fragments.

A number of novel di- and triorganotin(IV) complexes 1-5 (Ph2SnL1, Ph2SnL2, Et2SnL2, Ph3SnL3, Ph3SnL4) with mono- or dianionic forms of thio-Schiff bases containing antioxidant sterically hindered phenol or catechol fragments were synthesized. Compounds 1-5 were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of complexes 1 and 2 in the crystal state were established by single-crystal X-ray analysis. The antioxidant activity of new complexes as radical scavengers was estimated in DPPH and ABTS assays. It was found that compounds 4 and 5 with free phenol or catechol fragments are more active in these tests than complexes 1-3 with tridentate O,N,S-coordinated ligands. The effect of compounds 1-5 on the promoted oxidative damage of the DNA by 2,2'-azobis(2-amidinopropane) dihydrochloride and in the process of rat liver (Wistar) homogenate lipid peroxidation in vitro was determined. Complexes 4 and 5 were characterized by more pronounced antioxidant activity in the reaction of lipid peroxidation in vitro than compounds 1-3. The antiproliferative activity of compounds 1-5 was investigated against MCF-7, HTC-116, and A-549 cell lines by an MTT test. The values of IC50 are significantly affected by the presence of free antioxidant fragments and the coordination site for binding.

Low-Coordinate Mixed Ligand NacNac Complexes of Rare Earth Metals.

We report the synthesis and characterization of two types of new mixed-ligand rare earth complexes: tetracoordinate (NacNacMes)Ln(BIANdipp) (Ln = Dy (1), Er (2) and Y (3)) and pentacoordinate (NacNacMes)Ln(APdipp)(THF) (Ln = Dy (4), Er (5) and Y (6)). The first three compounds were prepared by the reaction of [(BIANDipp)LnI] with potassium ß-diketiminate. The salt metathesis of ß-diketiminato-supported rare earth dichlorides (NacNacMes)LnCl2(THF)2 with sodium o-amidophenolate results in compounds 4-6. The crystal structures of complexes 1-6 were determined by single-crystal analysis. The combination of bulky monoanionic N-mesityl-substituted ß-diketiminates with sterically hindered redox-active ligands led to the very low coordination numbers of rare earths and strong distortion of the chelate ligands.

Heteroligand α-Diimine-Zn(II) Complexes with O,N,O'- and O,N,S-Donor Redox-Active Schiff Bases: Synthesis, Structure and Electrochemical Properties.

A number of novel heteroligand Zn(II) complexes (1-8) of the general type (Ln)Zn(NN) containing O,N,O'-, O,N,S-donor redox-active Schiff bases and neutral N,N'-chelating ligands (NN) were synthesized. The target Schiff bases LnH2 were obtained as a result of the condensation of 3,5-di-tert-butyl-2-hydroxybenzaldehyde with substituted o-aminophenols or o-aminothiophenol. These ligands with combination with 2,2'-bipyridine, 1,10-phenanthroline, and neocuproine are able to form stable complexes upon coordination with zinc(II) ion. The molecular structures of complexes 4∙H2O, 6, and 8 in crystal state were determined by means of single-crystal X-ray analysis. In the prepared complexes, the redox-active Schiff bases are in the form of doubly deprotonated dianions and act as chelating tridentate ligands. Complexes 6 and 8 possess a strongly distorted pentacoordinate geometry while 4∙H2O is hexacoordinate and contains water molecule coordinated to the central zinc atom. The electrochemical properties of zinc(II) complexes were studied by the cyclic voltammetry. For the studied complexes, O,N,O'- or O,N,S-donor Schiff base ligands are predominantly involved in electrochemical transformations in the anodic region, while the N,N'-coordinated neutral nitrogen donor ligands demonstrate the electrochemical activity in the cathode potential range. A feature of complexes 5 and 8 with sterically hindered tert-butyl groups is the possibility of the formation of relatively stable monocation and monoanion forms under electrochemical conditions. The values of the energy gap between the boundary redox orbitals were determined by electrochemical and spectral methods. The parameters obtained in the first case vary from 1.97 to 2.42 eV, while the optical bang gap reaches 2.87 eV.

Binuclear Triphenylantimony(V) Catecholates through N-Donor Linkers: Structural Features and Redox Properties.

A series of binuclear triphenylantimony(V) bis-catecholato complexes 1-11 of the type (Cat)Ph3Sb-linker-SbPh3(Cat) was prepared by a reaction of the corresponding mononuclear catecholates (Cat)SbPh3 with a neutral bidentate donor linker ligands pyrazine (Pyr), 4,4'-dipyridyl (Bipy), bis-(pyridine-4-yl)-disulfide (PySSPy), and diazobicyclo[2,2,2]octane (DABCO) in a dry toluene: Cat = 3,6-di-tert-butyl-catecholate (3,6-DBCat), linker = Pyr (1); PySSPy (2); Bipy (3); DABCO (4); Cat = 3,5-di-tert-butyl-catecholate (3,5-DBCat), linker = Bipy (5); DABCO (9); Cat = 4,5-(piperazine-1,4-diyl)-3,6-di-tert-butylcatecholate (pip-3,6-DBCat), linker = Bipy (6); DABCO (10); Cat = 4,5-dichloro-3,6-di-tert-butylcatecholate (4,5-Cl2-3,6-DBCat), linker = Bipy (7); DABCO (11); and Cat = 4,5-dimethoxy-3,6-di-tert-butylcatecholate (4,5-(MeO)2-3,6-DBCat), linker = Bipy (8). The same reaction of (4,5-Cl2-3,6-DBCat)SbPh3 with DABCO in an open atmosphere results in a formation of 1D coordination polymer {[(4,5-Cl2-3,6-DBCat)SbPh3·H2O]·DABCO}n (12). Bis-catecholate complex Ph3Sb(Cat-Spiro-Cat)SbPh3 reacts with Bipy as 1:1 yielding a rare macrocyclic tetranuclear compound {Ph3Sb(Cat-Spiro-Cat)SbPh3∙(Bipy)}2 (13). The molecular structures of 1, 3, 4, 5, 8, 10, 12, and 13 in crystal state were established by single-crystal X-ray analysis. Complexes demonstrate different types of relative spatial positions of mononuclear moieties. The nature of chemical bonds, charges distribution, and the energy of Sb...N interaction were investigated in the example of complex 5. The electrochemical behavior of the complexes depends on the coordinated N-donor ligand. The coordination of pyrazine, Bipy, and PySSPy at the antimony atom changes their mechanism of electrooxidation: instead of two successive redox stages Cat/SQ and SQ/Cat, one multielectron stage was observed. The coordination of the DABCO ligand is accompanied by a significant shift in the oxidation potentials of the catecholate ligand to the cathodic region (by 0.4 V), compared to the initial complex.

Heteroligand Metal Complexes with Extended Redox Properties Based on Redox-Active Chelating Ligands of o-Quinone Type and Ferrocene.

A combination of different types of redox-active systems in one molecule makes it possible to create coordination compounds with extended redox abilities, combining molecular and electronic structures determined by the features of intra- and intermolecular interactions between such redox-active centres. This review summarizes and analyses information from the literature, published mainly from 2000 to the present, on the methods of preparation, the molecular and electronic structure of mixed-ligand coordination compounds based on redox-active ligands of the o-benzoquinone type and ferrocenes, ferrocene-containing ligands, the features of their redox properties, and some chemical behaviour.

Synthesis and Antioxidant Activity of New Catechol Thioethers with the Methylene Linker.

Novel catechol thio-ethers with different heterocyclic substituents at sulfur atom were prepared by reacting 3,5-di-tert-butyl-6-methoxymethylcatechol with functionalized thiols under acidic conditions. A common feature of compounds is a methylene bridge between the catechol ring and thioether group. Two catechols with the thio-ether group, bound directly to the catechol ring, were also considered to assess the effect of the methylene linker on the antioxidant properties. The crystal structures of thio-ethers with benzo-thiazole moieties were established by single-crystal X-ray analysis. The radical scavenging and antioxidant activities were determined using 2,2'-diphenyl-1-picrylhydrazyl radical test, ABTS∙+, CUPRAC (TEAC) assays, the reaction with superoxide radical anion generated by xanthine oxidase (NBT assay), the oxidative damage of the DNA, and the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro. Most catechol-thioethers exhibit the antioxidant effect, which varies from mild to moderate depending on the model system. The dual anti/prooxidant activity characterizes compounds with adamantyl or thio-phenol substituent at the sulfur atom. Catechol thio-ethers containing heterocyclic groups (thiazole, thiazoline, benzo-thiazole, benzo-xazole) can be considered effective antioxidants with cytoprotective properties. These compounds can protect molecules of DNA and lipids from the different radical species.

Triphenylantimony(V) Catecholates of the Type (3-RS-4,6-DBCat)SbPh3-Catechol Thioether Derivatives: Structure, Electrochemical Properties, and Antiradical Activity.

A new series of triphenylantimony(V) 3-alkylthio/arylthio-substituted 4,6-di-tert-butylcatecholates of the type (3-RS-4,6-DBCat)SbPh3, where R = n-butyl (1), n-hexyl (2), n-octyl (3), cyclopentyl (4), cyclohexyl (5), benzyl (6), phenyl (7), and naphthyl-2 (8), were synthesized from the corresponding catechol thioethers and Ph3SbBr2 in the presence of a base. The crystal structures of 1, 2, 3, and 5 were determined by single-crystal X-ray analysis. The coordination polyhedron of 1-3 is better described as a tetragonal pyramid with a different degree of distortion, while that for 5- was a distorted trigonal bipyramid (τ = 0.014, 0.177, 0.26, 0.56, respectively). Complexes demonstrated different crystal packing of molecules. The electrochemical oxidation of the complexes involved the catecholate group as well as the thioether linker. The introduction of a thioether fragment into the aromatic ring of catechol ligand led to a shift in the potential of the "catechol/o-semiquinone" redox transition to the anodic region, which indicated the electron-withdrawing nature of the RS group. The radical scavenging activity of the complexes was determined in the reaction with DPPH radical.

Imine-Based Catechols and o-Benzoquinones: Synthesis, Structure, and Features of Redox Behavior.

Novel sterically hindered catechols of the type 3-(RN=CH)-4,6-DBCatH2 with iminoalkyl or iminoaryl groups in the third position of the aromatic ring have been synthesized and characterized in detail. The o-benzoquinones 3-(RN=CH)-4,6-DBBQ have been synthesized by the oxidation of the corresponding catechols. The oxidation of methylimino-substituted catechol with K3[Fe(CN)6] in alkaline medium leads to the formation of two products: o-quinone and diene-dione, the product of the water addition to the corresponding o-quinone. Some o-benzoquinones react with water or methanol to yield products of water or methanol addition. A prototropic tautomerism is characteristic of catecholaldimines: a quinomethide form is observed in the case of aliphatic amine derivatives, while aryl-substituted catecholaldimines can exist both in the catechol and quinomethide forms in the crystalline state. The formation of dimeric structures motifs is observed in crystals. The electrochemical oxidation of imino-based catechols proceeds via two one-electron processes; the second wave is quasi-reversible, which is unusual for catechols.

Polyfunctional Sterically Hindered Catechols with Additional Phenolic Group and Their Triphenylantimony(V) Catecholates: Synthesis, Structure, and Redox Properties.

New polyfunctional sterically hindered 3,5-di-tert-butylcatechols with an additional phenolic group in the sixth position connected by a bridging sulfur atom-(6-(CH2-S-tBu2Phenol)-3,5-DBCat)H2 (L1), (6-(S-tBu2Phenol)-3,5-DBCat)H2 (L2), and (6-(S-Phenol)-3,5-DBCat)H2 (L3) (3,5-DBCat is dianion 3,5-di-tert-butylcatecolate)-were synthesized and characterized in detail. The exchange reaction between catechols L1 and L3 with triphenylantimony(V) dibromide in the presence of triethylamine leads to the corresponding triphenylantimony(V) catecholates (6-(CH2-S-tBu2Phenol)-3,5-DBCat)SbPh3 (1) and (6-(S-Phenol)-3,5-DBCat)SbPh3 (2). The electrochemical properties of catechols L1-L3 and catecholates 1 and 2 were investigated using cyclic voltammetry. The electrochemical oxidation of L1-L3 at the first stage proceeds with the formation of the corresponding o-benzoquinones. The second process is the oxidation of the phenolic moiety. Complexes 1 and 2 significantly expand their redox capabilities, owing to the fact that they can act as the electron donors due to the catecholate metallocycle capable of sequential oxidations, and as donors of the hydrogen atoms, thus forming a stable phenoxyl radical. The molecular structures of the free ligand L1 and complex 1 in the crystal state were determined by single-crystal X-ray analysis.

Ferrocene-Containing Tin(IV) Complexes Based on o-Benzoquinone and o-Iminobenzoquinone Ligands. Synthesis, Molecular Structure, and Electrochemical Properties.

The addition of different substituted o-benzoquinones and o-iminobenzoquinones to tin(II) bis(o-iminophenolates) of the types (Fc-IP)2SnII and (Fc-4,6-IP)2SnII (where Fc-IP is anion 2-(ferrocenylmethyleneamino)phenolate [Fc-C(H)═N(C6H4)O-] and Fc-4,6-IP is anion 2-(ferrocenylmethyleneamino)-4,6-di-tert-butylphenolate [Fc-C(H)═N(4,6-tBu-C6H2)O-]) in tetrahydrofuran leads to the oxidation of Sn(II) to Sn(IV) with formation of the corresponding tin(IV) catecholates (Fc-4,6-IP)2SnIV(3,6-Cat) (1), (Fc-IP)2SnIV(3,6-Cat) (2), (Fc-4,6-IP)2SnIV(4-Cl-3,6-Cat) (3), (Fc-IP)2SnIV(4-Cl-3,6-Cat) (4), (Fc-4,6-IP)2SnIV(4,5-Cl2-3,6-Cat) (5), and (Fc-IP)2SnIV(4,5-Cl2-3,6-Cat) (6) or the o-amidophenolates (Fc-4,6-IP)2SnIV(AP-Me) (7), (Fc-IP)2SnIV(AP-iPr) (8), and (Fc-4,6-IP)2SnIV(AP-iPr) (9). Here ligands 3,6-Cat, 4-Cl-3,6-Cat, and 4,5-Cl2-3,6-Cat are dianions 3,6-di-tert-butyl-, 4-chloro-3,6-di-tert-butyl-, and 4,5-dichloro-3,6-di-tert-butylcatecholates, respectively, and AP-Me and AP-iPr are dianions 4,6-di-tert-butyl-N-(2,6-dimethylphenyl)-o-amidophenolate and 4,6-di-tert-butyl-N-(2,6-diisopropylphenyl)-o-amidophenolate, respectively. Complexes 1-9 have been characterized in detail by IR spectroscopy, cyclic voltammetry, and 1H, 13C, and 119Sn NMR spectroscopy. The molecular structures of tin(IV) complexes 5, 7, and 9 in the crystalline state were determined by single-crystal X-ray diffraction analysis. Complexes demonstrate a series of successive oxidations involving alternately catecholato/o-amidophenolato centers and ferrocenyl moieties. The relative oxidation potentials of these redox centers depend on the acceptor properties of the redox-active chelating O,O' or O,N ligand. An increase in the acceptor properties of redox-active o-quinonato-type ligands leads to an increase in the oxidation potentials of redox ligands as well as the following oxidation of ferrocenyl group(s). In two series of complexes, (Fc-4,6-L)2SnL' and (Fc-L)2SnL', where L' is AP-iPr, AP-Me, 3,6-Cat, 4-Cl-3,6-Cat, and 4,5-Cl2-3,6-Cat, a more pronounced convergence of the oxidation potentials of the redox-active o-quinonato ligand and ferrocenyl group occurs in the series (Fc-L)2SnL'.

Catechol thioethers with physiologically active fragments: Electrochemistry, antioxidant and cryoprotective activities.

A number of asymmetrical thioethers based on 3,5-di-tert-butylcatechol containing sulfur atom bonding with physiologically active groups in the sixth position of aromatic ring have been synthesized and the electrochemical properties, antioxidant, cryoprotective activities of new thioethers have been evaluated. Cyclic voltammetry was used to estimate the oxidation potentials of thioethers in acetonitrile. The electrooxidation of compounds at the first stage leads to the formation of o-benzoquinones. The antioxidant activities of the compounds were determined using 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) assay, experiments on the oxidative damage of the DNA, the reaction of 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) induced glutathione depletion (GSH), the process of lipid peroxidation of rat liver (Wistar) homogenates in vitro, and iron(II) chelation test. Compounds 1-9 have greater antioxidant effectiveness than 3,5-di-tert-butylcatechol (CatH2) in all assays. The variation of physiologically active groups at sulfur atom allows to regulate lipophilic properties and antioxidant activity of compounds. Thioethers 3, 4 and 7 demonstrate the combination of radical scavenging, antioxidant activity and iron(II) binding properties. The researched compounds 1-9 were studied as possible cryoprotectants of the media for cryopreservation of the Russian sturgeon sperm. Novel cryoprotective additives in cryomedium reduce significantly the content of membrane-permeating agent (DMSO). A cryoprotective effect of an addition of the catechol thioethers depends on the structure of groups at sulfur atom. The cryoprotective properties of compounds 3, 4 and 7 are caused by combination of catechol fragment, bonded by a thioether linker with a long hydrocarbon chain and a terminal ionizable group or with a biologically relevant acetylcysteine residue.

Deprotonation of Benzoxazolium Salt: Trapping of a Radical-Cation Intermediate.

The deprotonation of N-2,6-diisopropylphenyl-substituted benzoxazolium tetrafluoroborate 1 with NaH results in the formation of electron-rich diaminodioxaethylene 2. The radical cation salt 2·+·BF4- is found to be an intermediate product in the redox reaction leading from 1 to 2.

Heteroligand o-Semiquinonato-Formazanato Cobalt Complexes.

Two novel heteroligand o-semiquinonato-formazanato cobalt complexes [Co(3,6-SQ)(Form)] (1) and [Co(3,6-SQ)2(Form)] (2) (3,6-SQ is 3,6-di-tert-butyl-o-benzosemiquinonate radical anion; Form is 1,3,5-triphenylformazanate anion) were synthesized and characterized in detail. The molecular structures of [Co(3,6-SQ)(Form)] and [Co(3,6-SQ)2(Form)] were determined by X-ray analysis. Magnetic susceptibility measurements and spectroscopic studies have shown that square-planar complex 1 is diamagnetic with a residual paramagnetism due to antiferromagnetic exchange metal-ligand. Complex 2 includes cobalt(III) in the low-spin state and two anionic-radical o-semiquinonato and one formazanate ligand.

Ferrocene-o-benzosemiquinonato tin(IV) electron-transfer complexes.

The interaction of ferrocene with tin(IV) o-benzosemiquinonato complexes in acetonitrile results in a reversible electron transfer (ET) from ferrocene to the redox-active ligand with the formation of electron-transfer complexes [(3,6-Cat)SnBr3](-)[Cp2Fe](+) (1) and [(3,6-Cat)(3,6-SQ)SnCl2](-)[Cp2Fe](+) (2), where 3,6-Cat is the 3,6-di-tert-butyl-catecholate dianion and 3,6-SQ is the 3,6-di-tert-butyl-o-benzosemiquinonato radical anion. The ET process and the solvent effect in the system "ferrocene-o-benzosemiquinonato tin(IV) complexes" were investigated on the basis of a combination of spectroscopic and X-ray diffraction methods. The molecular structures of 1 and 2 were confirmed by X-ray analysis. Complex 2 demonstrates the ferromagnetic coupling in the linear chain alternating ···D(+•)A(-•)D(+•)A(-•)··· motif.

Reversible binding of molecular oxygen to catecholate and amidophenolate complexes of SbV: electronic and steric factors.

Edge of reactivity: The reactions of reversible binding of molecular oxygen to catecholate and amidophenolate complexes of Sb(V) are investigated by analyzing the position of electronic (E(HOMO)) and steric (G-parameter) factors. The optimal electronic and steric parameters for such type reactions are found.

Experimental and theoretical investigation of topological and energetic characteristics of Sb complexes reversibly binding molecular oxygen.

The experimental distribution of electron density in Ph(3)(4,5-OMe-3,6-Bu(t)-Cat)Sb·MeCN (1*) and Ph(3)(4,5-N(2)C(4)H(6)-3,6-Bu(t)-Cat)Sb·MeOH (2*) complexes was studied. According to atoms in molecules theory, the Sb-C(Ph), Sb-O(catecholate), and Sb···N(O) bonds are intermediate, whereas the O-C and C-C bonds are covalent, respectively. The energy of the Sb···N(MeCN) and Sb···O(MeOH) bonds are 7.0 and 11.3 kcal/mol according to the Espinosa equation. Density functional theory and Hartree-Fock calculations were carried out for a series of catecholate and amidophenolate complexes of antimony(V). It was shown that such calculations reliably reproduce geometrical and topological parameters and therefore can be used for a criterion search of dioxygen reversible binding by the catecholate and amidophenolate complexes of antimony(V). It was found that the "critical" value of the HOMO energy vary in the range from -5.197 to -5.061 eV for reversible binding of dioxygen complexes. This can serve as a thermodynamic criterion to predict the possibility of the dioxygen reversible binding by the catecholate and amidophenolate complexes of Sb(V). The HOMO energies correlate with the conversion of the catecholate and amidophenolate complexes in corresponding spiroendoperoxide derivatives as well. The contribution of the atom orbitals of the carbon atoms in the five-membered metallocycle to HOMO in complexes with different substitutes in the 4- and 5-positions of the catecholate ligand allows predicting the place of dioxygen addition.

Triphenylantimony(v) catecholates and o-amidophenolates: reversible binding of molecular oxygen.

Novel neutral antimony(V) complexes were isolated as crystalline materials and characterized by IR and NMR spectroscopy: o-amidophenolate complexes [4,6-di-tert-butyl-N-(2,6-dimethylphenyl)-o-amidophenolato]triphenylantimony(V) (Ph3Sb[AP-Me], 1) and [4,6-di-tert-butyl-N-(2,6-diisopropylphenyl)-o-amidophenolato]triphenylantimony(v) (Ph3Sb[AP-iPr], 2); catecholate complexes (3,6-di-tert-butyl-4-methoxycatecholato)triphenylantimony(V) (Ph3Sb[(MeO)Cat], 3), its methanol solvate 3CH3OH (4); (3,6-di-tert-butyl-4,5-di-methoxycatecholato)triphenylantimony(V) (Ph3Sb[(MeO)2Cat], 5) and its acetonitrile solvate 5CH3CN (6). Complexes 1-7 were synthesized by oxidative addition of the corresponding o-iminobenzoquinones or o-benzoquinones to Ph3Sb. In the case of the phenanthrene-9,10-diolate (PhenCat) ligand, two different complexes were isolated: Ph3Sb[PhenCat] (7) and [Ph4Sb]+[Ph2Sb(PhenCat)2]- (8). Complexes 7 and 8 were found to be in equilibrium in solution. Molecular structures of 2, 4, 6, and 8 were determined by X-ray crystallography. Complexes 1-7 reversibly bind molecular oxygen to yield Ph3Sb[L-Me]O2 (9), Ph3Sb[L-iPr]O2 (10), Ph3Sb[(MeO)L']O2 (11), Ph3Sb[(MeO)2L']O2 (12) and Ph3Sb[PhenL']O2 (13), which contain five-membered trioxastibolane species (where L is the O,O',N-coordinated derivative of a 1-hydroperoxy-6-(N-aryl)-iminocyclohexa-2,4-dienol, and L' the O,O',O''-coordinated derivative of 6-hydroperoxy-6-hydroxycyclohexa-2,4-dienone). Complexes 9-13 were characterized by IR and 1H NMR spectroscopy and X-ray crystallography.