Biomedical subjects
Reinhold Tacke
Publications and source records attributed to Reinhold Tacke.
(R)-sila-venlafaxine: a selective noradrenaline reuptake inhibitor for the treatment of emesis.
Sila-substitution of drugs (the carbon/silicon switch) is a concept that is being successfully used for the development of new chemical entities. The (R)-sila-analogue of the antidepressant venlafaxine is devoid of the serotonin reuptake inhibition observed with the marketed drug, leading to a selective noradrenaline reuptake inhibitor displaying anti-emetic properties.
Synthesis and structural characterization of neutral higher-coordinate silicon(IV) complexes with tridentate dianionic chelate ligands.
The neutral pentacoordinate silicon(IV) complexes 8 and 9 with an SiO2N3 skeleton and the neutral hexacoordinate silicon(IV) complex 10.1/2 CH3CN with an SiO4N2 skeleton were synthesized, starting from tetra(cyanato-N)silane or tetra(thiocyanato-N)silane. Compounds 8 and 9 contain one tridentate dianionic ligand derived from 4-[(2-hydroxyphenyl)amino]pent-3-en-2-one and two monodentate singly charged cyanato-N or thiocyanato-N ligands bound to the silicon(IV) coordination center, whereas the silicon(IV) center of 10 is coordinated by two of these tridentate dianionic ligands. All compounds were characterized by single-crystal X-ray diffraction and solid-state and solution NMR spectroscopy. To get more information about the stereochemistry of the compounds studied, the experimental investigations were complemented by computational studies.
A zwitterionic spirocyclic pentacoordinate silicon compound synthesized in water by Si--O and Si--C bond cleavage.
Explore the source record for details and available documents.
Synthesis and structural characterization of novel neutral hexacoordinate silicon(IV) complexes with SiO2N4 skeletons containing cyanato-N or thiocyanato-N ligands.
A series of novel hexacoordinate silicon(IV) complexes with an SiO2N4 skeleton (compounds (OC-6-12)-3, (OC-6-12)-4, (OC-6-12)-5, (OC-6-12)-6, and (OC-6-2'2)-7) were synthesized, starting from Si(NCO)4 or Si(NCS)4. These compounds contain (i) two bidentate O,N-chelate ligands (or one tetradentate O,N,N,O-chelate ligand) derived from 4-aminopent-3-en-2-ones of the formula type Me-C(NRH)=CH-C(O)-Me (R = organyl) and (ii) two monodentate cyanato-N or thiocyanato-N ligands. Formally, the bidentate singly negatively charged O,N-chelate ligands (tetradentate 2-fold negatively charged O,N,N,O-chelate ligand) behave as ligands of the imino-enolato type. In addition, the adduct trans-8 was synthesized by reaction of Si(NCS)4 with 2 molar equiv of Me-C(Ni-PrH)=CH-C(O)-Me. This hexacoordinate silicon(IV) complex contains (i) four monodentate thiocyanato-N ligands and (ii) two neutral monodentate ligands of the iminio-enolato type. All compounds synthesized were structurally characterized by single-crystal X-ray diffraction and solid-state and solution NMR spectroscopy. To get more information about the stereochemistry of these compounds, the experimental investigations were complemented by computational studies.
Behavior of tri(n-butyl)ammonium bis[citrato(3-)-O1,O3,O6]silicate in aqueous solution: analysis of a sol-gel process by small-angle neutron scattering.
The racemic hexacoordinate silicon(IV) complex tri(n-butyl)ammonium bis[citrato(3-)-O1,O3,O6]silicate (1) was synthesized by treatment of Si(OMe)4 with 2 molar equiv of citric acid and 2 molar equiv of N(n-Bu)3. The corresponding germanium analogue, tri(n-butyl)ammonium bis[citrato(3-)-O1,O3,O6]germanate (5; structurally characterized by single-crystal X-ray diffraction), was obtained analogously, starting from Ge(OMe)4. Upon dissolution in water, the lambda6Si-silicate dianion of 1 hydrolyzes spontaneously (formation of Si(OH)4 and citric acid), whereas the lambda6Ge-germanate dianion of 5 was found to be stable in water. Aqueous "solutions" of 1, with concentrations that are significantly higher than the saturation concentration of Si(OH)4, look absolutely clear over a period of several weeks; however, in reality, these solutions are sols with very small particles that slowly grow with time and finally form a gel that precipitates. This sol-gel process was monitored by small-angle neutron scattering (SANS). For reasons of comparison, an aqueous solution of the hydrolytically stable germanium compound 5 was also studied by the SANS technique.
Spirocyclic zwitterionic lambda5Si-silicates with two bidentate ligands derived from alpha-amino acids or alpha-hydroxycarboxylic acids: synthesis, structure, and stereodynamics.
A series of zwitterionic lambda(5)Si-silicates with a (2,2,6,6-tetramethylpiperidinio)methyl group and two identical bidentate ligands derived from glycine, (S)-alanine, (S)-phenylalanine, glycolic acid, (S)-lactic acid, (S)-3-phenyllactic acid, or (S)-mandelic acid were synthesized and structurally characterized (solution and solid-state NMR spectroscopy; single-crystal X-ray diffraction). The chiral lambda(5)Si-silicates with ligands derived from optically active alpha-amino acids or alpha-hydroxycarboxylic acids were isolated as enantiomerically and diastereomerically pure compounds that undergo a (Lambda)/(Delta)-epimerization in solution.
Silicon chemistry as a novel source of chemical diversity in drug design.
The use of organosilicon chemistry in drug design is reviewed. The field of bioorganosilicon chemistry, which sprung up in the 1970s to exploit the opportunities of silicon for drug design, is currently being developed into a practical and commercial enterprise. This review is mainly focused on two different approaches: (i) synthesizing a silicon analog of a known drug in which one carbon atom has been replaced by a silicon atom, with the rest of the molecule being identical (carbon/silicon switch, sila-substitution); (ii) synthesizing completely new silicon-based classes of compounds (the carbon analogs of which do not exist) that exploit specific features of silicon chemistry to address a well-validated target.
Dianionic complexes with hexacoordinate silicon(IV) or germanium(IV) and three bidentate ligands of the hydroximato(2-) type: syntheses and structural characterization in the solid state.
Reaction of Si(OMe)(4) with acetohydroxamic acid or benzohydroxamic acid and HNMe(2) (molar ratio 1:3:2) in MeCN yielded dimethylammonium fac-tris[acetohydroximato(2-)]silicate (fac-5) and N,N-dimethylacetamidinium fac-tris[benzohydroximato(2-)]silicate (fac-8), respectively. Reaction of Si(OMe)(4) with benzohydroxamic acid and HNMe(2) (molar ratio 1:3:2) or ethane-1,2-diamine (molar ratio 1:3:1) in MeOH gave dimethylammonium fac-tris[benzohydroximato(2-)]silicate-methanol (fac-6.MeOH) and ethane-1,2-diammonium mer-tris[benzohydroximato(2-)]silicate-dimethanol (mer-9.2MeOH), respectively. Reaction of Ge(OMe)(4) with benzohydroxamic acid and HNMe(2) (molar ratio 1:3:2) in MeOH resulted in the formation of dimethylammonium fac-tris[benzohydroximato(2-)]germanate-methanol (fac-7.MeOH). Single-crystal X-ray diffraction studies showed that the Si(Ge)-coordination polyhedra of the racemic hexacoordinate silicon (germanium) compounds fac-5, fac-6.MeOH, fac-7.MeOH, fac-8, and mer-9.2MeOH are distorted octahedra. All compounds were additionally characterized by solid-state VACP/MAS NMR studies ((13)C, (15)N, (29)Si). The structural investigations were complemented by computational studies of the dianions of fac-5 and mer-5.
The hexacoordinate silicate dianions mer-tris[glycolato(2-)-O(1),O(2)]silicate and fac-tris[benzilato(2-)-O(1),O(2)]silicate: syntheses and structural characterization.
Treatment of tetramethoxysilane with glycolic acid and morpholine (molar ratio 1:3:2) in methanol, followed by crystallization from methanol/tetrahydrofuran, yielded morpholinium mer-tris[glycolato(2-)-O(1),O(2)]silicate (mer-7). Treatment of benzilic acid with sodium hydride, followed by addition of tetrachlorosilane and triethylamine (molar ratio 3:4:1:2), afforded, after crystallization from 1,4-dioxane/acetonitrile/diethyl ether/n-pentane, triethylammonium fac-tris[benzilato(2-)-O(1),O(2)]silicate-hemi-1,4-dioxane (fac-8.(1)/(2)C(4)H(8)O(2)). Single-crystal X-ray diffraction studies showed that the Si-coordination polyhedra of the hexacoordinate silicon(IV) complexes mer-7 and fac-8.(1)/(2)C(4)H(8)O(2) are distorted octahedra. Both compounds were additionally characterized by solid-state VACP/MAS NMR studies ((13)C, (29)Si), and fac-8.(1)/(2)C(4)H(8)O(2) was studied in solution by (1)H, (13)C, and (29)Si NMR experiments. The structural investigations were complemented by computational studies (MP2 studies, TZP level) of the dianions of fac-7 and mer-7.
Pentacoordination of Silicon by Four Covalent Si-S Bonds and One Covalent Si-C Bond This work was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie.
Explore the source record for details and available documents.