Selective methoxy ether cleavage of 2,6-dimethoxyphenol followed by a selective acylation.

A Friedel-Crafts reaction of 2,6-dimethoxyphenol in the presence of aluminum chloride and propanoyl or butanoyl chlorid, respectively, lead, at elevated temperatures, to a selective cleavage of one of the methoxy groups followed by a selective acylation of the meta position with respect to the phenolic hydroxyl group. Under the same reaction conditions 2-methoxyphenol doesn't get demethylated; a mechanism to account for these findings is proposed. This reaction gives access to a variety of ortho-acylated catechols. Substituted catechols are widely used in supramolecular chemistry and are precursors of pesticides, flavors and fragrances. Additionally, catechol moieties are found in various natural products.

Inhibitory effects of ethacrynic acid analogues lacking the α,ß-unsaturated carbonyl unit and para-acylated phenols on human cancer cells.

A series of ethacrynic acid analogues, lacking the α,ß-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, Hs578Ts(i)8 as well as of human prostate cancer cells, C4-2B. These cell lines provide a good model system to study migration and invasion, since they represent metastatic cancer. Our studies show that ethacrynic acid analogues with methyl substituents at the aromatic ring demonstrate no inhibitory effect on the migration of both cancer cell lines, whereas a precursor in the synthesis of these ethacrynic acid analogues (II-1, a para-acylated m-cresol) is an excellent inhibitor of the migration of both cancer cell lines.

Ethacrynic acid analogues lacking the alpha,beta-unsaturated carbonyl unit--potential anti-metastatic drugs.

A series of ethacrynic acid analogues, lacking the alpha,beta-unsaturated carbonyl unit, was synthesized and subsequently evaluated for their ability to inhibit the migration of human breast cancer cells, MCF-7/AZ. Several of the analogues were already active in the low micromolar range, whereas ethacrynic acid itself shows no potential to inhibit the migration of these cancer cells. Preliminary studies show that the presence of one or more methoxy groups at the phenyl ring of ethacrynic acid is important in order for the ethacrynic acid analogues to demonstrate an inhibitory effect on the migration.

Self-assembly and host-guest chemistry of big metallosupramolecular M4L4 tetrahedra.

Metallosupramolecular tetrahedra M8[L4Ti4] are easily obtained by self-assembly from the triangular ligands L-H6 and titanoyl bis(acetylacetonate) in the presence of alkali metal carbonates as base. All the complexes can be well characterized by 1H NMR in combination with ESI FT-ICR MS. Force field calculations reveal that the tetrahedra show Ti-Ti separations of 17 angstroms ([L1(4)Ti4]8-) and 23.5 angstroms ([L2(4)Ti4]8-), respectively, leading to huge internal cavities. The cavity is readily shielded in the case of L1 but possesses big pores with the bigger ligand L2. [L1(4)Ti4]8- was used to investigate the host-guest chemistry of these container molecules and it was found that cationic organic guest species like anilinium can be introduced in the interior of the complex. Inclusion is nicely followed by NMR spectroscopy. Upon addition of one equivalent of guest the symmetry of the tetrahedron is lost but is regained after addition of significantly more than four equivalents.

Hierarchical assembly of helicate-type dinuclear titanium(IV) complexes.

The ligands 4-7-H(2) were used in coordination studies with titanium(IV) and gallium(III) ions to obtain dimeric complexes Li(4)[(4-7)(6)Ti(2)] and Li(6)[(4/5a)(6)Ga(2)]. The X-ray crystal structures of Li(4)[(4)(6)Ti(2)], Li(4)[(5b)(6)Ti(2)], and Li(4)[(7a)(6)Ti(2)] could be obtained. While these complexes are triply lithium-bridged dimers in the solid state, a monomer/dimer equilibrium is observed in solution by NMR spectroscopy and ESI FT-ICR MS. The stability of the dimer is enhanced by high negative charges (Ti(IV) versus Ga(III)) of the monomers, when the carbonyl units are good donors (aldehydes versus ketones and esters), when the solvent does not efficiently solvate the bridging lithium ions (DMSO versus acetone), and when sterical hindrance is minimized (methyl versus primary and secondary carbon substituents). The dimer is thermodynamically favored by enthalpy as well as entropy. ESI FT-ICR mass spectrometry provides detailed insight into the mechanisms with which monomeric triscatecholate complexes as well as single catechol ligands exchange in the dimers. Tandem mass spectrometric experiments in the gas phase show the dimers to decompose either in a symmetric (Ti) or in an unsymmetric (Ga) fashion when collisionally activated. The differences between the Ti and Ga complexes can be attributed to different electronic properties and a charge-controlled reactivity of the ions in the gas phase. The complexes represent an excellent example for hierarchical self-assembly, in which two different noncovalent interactions of well balanced strengths bring together eleven individual components into one well-defined aggregate.

5,5'-Diamino-2,2'-bipyridine: a versatile building block for the synthesis of bipyridine/catechol ligands that form homo- and heteronuclear helicates.

Herein we present an improved synthesis of 5,5'-diamino-2,2'-bipyridine (1) starting from the pyrrole-protected aminopyridine 4. By standard reactions 1 can easily be transformed into the imine- or amide-bridged dicatechol-bipyridine ligands L1-H4 and L2-H4. Whereas ligand L1 readily forms homodinuclear helicates [(L1)3Ti2]4-, the attempted formation of mono-, tri-, or even oligonuclear coordination compounds from this ligand did not work. However, the amide-connected ligand L2 affords mononuclear ([(L2-H4)PdCl2], [(L2-H4)3Zn]2+), dinuclear ([(L2)3Ti2]4-), and heterotrinuclear coordination compounds ([(L2)3Ti2Zn]2-).

Catechol imine ligands: from helicates to supramolecular tetrahedra.

Di- and tricatechol imines are easily accessible by condensation of appropriate amines with 2,3-dihydroxybenzaldehyde. Dicatechol imines can be used for the alkali metal template-directed self-assembly of dinuclear triple-stranded helicates or meso-helicates with high diastereoselectivity. Tricatechol imines lead in self-assembly processes to metallosupramolecular 4 [ratio] 4 tetrahedra with a huge internal cavity, which is able to encapsulate guest species. Hereby the special features of the imine unit can be used to control the outcome of the self-assembly process.

Dicatechol-diimines: easily accessible ligands for the self-assembly of dinuclear triple-stranded helicates.

Dicatechol ligands 3b-g-H4 are simply prepared by imine formation of 2,3-dihydroxybenzaldehyde 2 with a series of different diamines 1b-g . An X-ray structural analysis was obtained for the butyl-bridged compound 3e-H4, showing an intramolecular proton transfer and the formation of a chinoidic "keto-amine" structure. The dicatechol derivatives 3b-g-H4 form dinuclear triple-stranded helicates M4[(3)3Ti2] with titanium(IV) ions in the presence of alkali-metal carbonate. For the phenyl- and the trans-1,4-cyclohexyl-bridged complexes, K4[(3b)3Ti2] and Na4[(3f)3Ti2], X-ray structures were obtained.

Long-range stereocontrol in the self-assembly of two-nanometer-dimensioned triple-stranded dinuclear helicates.

A series of bisimine-bridged dicatechol ligands 2-H(4)-5-H(4) were synthesized and were used to prepare triple-stranded dinuclear helicate-type complexes with a length of up to more than 2 nm. X-ray structural analyses of Na(4)[(2)(3)V(2)], Na(4)[(3)(3)Ti(2)], Na(4)[(4)(3)Ti(2)], and Na(4)[(5)(3)Ti(2)], as well as temperature-dependent NMR investigations of Na(4)[(4)(3)Ti(2)] and Na(4)[(5)(3)Ti(2)] show that, in the case of the rigid linear ligands 2 and 3, and of the ligand 5, which possesses C(2h) symmetry in its idealized structure, homochiral helicates are diastereoselectively formed. Ligand 4, on the other hand, with idealized C(2v) symmetry, leads with surprisingly high selectivity to the formation of the heterochiral meso-helicate. This is attributed to the ability of ligand 4 to adopt a less-restricted conformation in the meso compound than in the helical complex. NMR investigations indicate that both complex units of Na(4)[(4)(3)Ti(2)] invert (LambdaDelta-->DeltaLambda) simultaneously, while in the case of Na(4)[(5)(3)Ti(2)] a stepwise racemization proceeds.

A metallosupramolecular tetrahedron with a huge internal cavity.

A huge molecular tetrahedral complex forms quantitatively by self-assembly from four ligands L-H6 and four titanium(IV) ions; in the solid state it encapsulates four [K(DIMF)3]+ units in its interior.