Variation of the Molecular Conformation, Shape, and Cavity Size in Dinuclear Metalla-Macrocycles Containing Hetero-Ditopic Dithiocarbamate-Carboxylate Ligands from a Homologous Series of N-Substituted Amino Acids.

A homologous series of dithiocarbamate ligands derived from N-substituted amino acids was reacted with different diorganotin dichlorides to give 18 diorganotin complexes. Spectroscopic and mass spectrometric analysis evidenced the formation of assemblies with six-coordinate tin atoms embedded in skewed-trapezoidal bipyramidal coordination environments of composition C2SnS2O2. Single-crystal X-ray diffraction analysis for three of the compounds revealed a one-dimensional polymeric structure for the complex with the ligand derived from 5-aminopentanoic acid, which through further intermolecular Sn···O interactions generated an overall two-dimensional coordination polymer containing 40-membered hexanuclear tin macrocycles. On the contrary, the ligands derived from 6-aminohexanoic and 8-aminooctanoic acid provided the expected 22- and 26-membered dinuclear macrocyclic structures. Density functional theory calculations for a representative series of macrocyclic complexes of composition [Me2SnLx]2 with Lx = ¯S2CN(Me)-(CH2)x-COO¯ (x = 3-12) enabled a detailed analysis of the variations in the molecular conformation, shape, and cavity size of the macrocycles in dependence of the aliphatic spacer. Because of odd-even effects, the difunctional ligands can adopt either a curved or a twisted-pincer shape, while the SnSxO4-x (x = 0-4) moieties can act either as linear or angular tectons with varying connectivity angles.

Synthesis, in vitro and in silico screening of ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetates as protein-tyrosine phosphatase 1B inhibitors.

The ethyl 2-(6-substituted benzo[d]thiazol-2-ylamino)-2-oxoacetate derivatives (OX 1-9) were prepared using a one-step reaction. The in vitro inhibitory activity of the compounds against protein tyrosine phosphatase 1B (PTP-1B) was evaluated. Compounds OX-(1, 6 and 7) were rapid reversible (mixed-type) inhibitors of PTP-1B with IC(50) values in the low micro-molar range. The most active compounds OX-(1, 6 and 7) were docked into the crystal structure of PTP-1B. Docking results indicate potential hydrogen bond interactions between the oxamate group in all compounds and the catalytic amino acid residues Arg221 and Ser216. The compounds were evaluated for their in vivo hypoglycemic activity, showing significant lowering of plasma glucose concentration in acute normoglycemic model and oral glucose tolerance test similarly at the effect exerted for hypoglycemic drug glibenclamide.

Macrocyclic diorganotin complexes of gamma-amino acid dithiocarbamates as hosts for ion-pair recognition.

The dimethyl-, di-n-butyl-, and diphenyltin(IV) dithiocarbamate (dtc) complexes [{R2Sn(L-dtc)}x] 1-7 (1, L = L1, R = Me; 2, L = L1, R = n-Bu; 3, L = L2, R = Me, x = infinity; 4, L = L2, R = n-Bu; 5, L = L3, R = Me, x = 2; 6, L = L3, R = n-Bu, x = 2; 7, L = L3, R = Ph, x = 2) have been prepared from a series of secondary amino acid (AA) homologues as starting materials: N-benzylglycine (alpha-AA derivative = L1), N-benzyl-3-aminopropionic acid (beta-AA derivative = L2), and N-benzyl-4-aminobutyric acid (gamma-AA derivative = L3). The resulting compounds have been characterized by elemental analysis, mass spectrometry, IR and NMR ((1)H, (13)C, and (119)Sn) spectroscopy, thermogravimetric analysis, and X-ray crystallography, showing that in all complexes both functional groups of the heteroleptic ligands are coordinated to the tin atoms. By X-ray diffraction analysis, it could be shown that [{Me2Sn(L2-dtc)}x] (3) is polymeric in the solid state, while the complexes derived from L3 (5-7) have dinuclear 18-membered macrocyclic structures of the composition [{R2Sn(L3-dtc)}2]. For the remaining compounds, it could not be established with certainty whether the structures are macrocyclic or polymeric. A theoretical investigation at the B3LYP/SBKJC(d,p) level of theory indicated that the alpha-AA-dtc complexes might have trinuclear macrocyclic structures. The macrocyclic complexes 5-7 have a double-calix-shaped conformation with two cavities large enough for the inclusion of aliphatic and aromatic guest molecules. They are self-complementary for the formation of supramolecuar synthons that give rise to 1D molecular arrangements in the solid state. Preliminary recognition experiments with tetrabutylammonium acetate have shown that the [{R2Sn(L3-dtc)}2] macrocycles 6 and 7 might interact simultaneously with anions (AcO(-)), which coordinate to the tin atoms, and organic cations (TBA(+)), which accommodate within the hydrophobic cavity (ion-pair recognition).

Synthesis and NMR configurational analysis of 1,3-imidazolidin-4-ones derived from (-)-(S)-phenylethylamine.

The preparation and NMR study in the solution state of (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one, (-)-(2R,1'S)- and (+)-(2S,1'S)-1-acetyl-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one, and (-)-(2S,1'S)- and (+)-(2R,1'S)-1-carboethoxy-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one are described. The orientations of acetyl, carboethoxy, and phenethyl groups attached to nitrogen atoms N-1 and N-2 were deduced from the proton and (13)C chemical shifts. The typical orientation of phenethyl group, which has the hydrogen H-6 syn and close to the oxygen of carbonyl C-4, was observed in (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one but not in the other four compounds; nevertheless, interpretation of chemical shifts based on the ring current effects correlated with the true configuration of the new stereogenic center at C-2. Four of these imidazolidinones were analyzed by X-ray diffraction to corroborate the configuration determined by NMR. The structures determined by X-ray diffraction revealed the existence of intramolecular hydrogen bonds capable to control the conformation of the phenethyl and acyl groups in the solution state.