Size matters, so does shape: Inhibition of transcription of T7 RNA polymerase by iron(II) clathrochelates

The Peculiarities of Ionization, Fragmentation and Association (Macrobicyclization) of Pseudoclathrochelate Zinc, Cobalt, Iron and Manganese(II) tris-Pyrazoloximates in the LDI Mass Spectra

“…«топологи-ческих лекарств» [3][4][5][6] и перспективных парамагнитных проб для использования в структурной биологии. [7,8] В связи с этим представляет несомненный интерес изуче-ние устойчивости и путей фрагментации этих клеточных комплексов как в растворах, так и в газовой фазе.…”

ESI-MS Study of Ionization Pathways and Cation-Receptor Properties of the Iron(II) Mono- and Bis-Clathrochelates

“…[1] Biological activity of such compounds as enzymatic regulators in the systems of biosynthesis of nucleic acids has recently started to attract much attention. [2,3] The interest of biochemists and molecular biologists in d-metal clathrochelates has been triggered by their high synthetic availability, (photo)chemical stability, and the activity of a series of iron(II) clathrochelates as efficient transcription inhibitors for the T7 RNA polymerase. [3] We have recently succeeded to boost the inhibitory activity of cage compounds by direct joining of two macrobicyclic fragments with a covalent bond, [4] while keeping all the advantages of clathrochelates as enzyme inhibitors in submicromolar range.…”

“…[2,3] The interest of biochemists and molecular biologists in d-metal clathrochelates has been triggered by their high synthetic availability, (photo)chemical stability, and the activity of a series of iron(II) clathrochelates as efficient transcription inhibitors for the T7 RNA polymerase. [3] We have recently succeeded to boost the inhibitory activity of cage compounds by direct joining of two macrobicyclic fragments with a covalent bond, [4] while keeping all the advantages of clathrochelates as enzyme inhibitors in submicromolar range. Such iron(II) bis-clathrochelates have an incredible chemical stability and low toxicity, are easy to synthesize from available and inexpensive initial compounds, and have favorable geometry allowing introduction of up to fourteen substituents.…”

“…These cage complexes have been also used as versatile guests to form strong supramolecular assemblies with blood transport proteins -serum albumins, but discriminating other globular proteins, [5] and have been shown to affect protein uncontrolled aggregation by changing the kinetics of insulin fibrillization and reducing the amount of amyloid fibrils formed and suppressing the formation of superfibrillar species as well. [6] This demonstrates huge potential of cage metal complexes as prospective antiviral and anticancer drug candidates (the so-called "topological drugs" [2][3][4][5][6] ). The cage complexes have been also proposed as molecular scaffolds for the design of multicentred molecular and supramolecular systems for the target delivery of an encapsulated radionuclide as well as (radio)diagnostic and (radio)therapeutic compounds (in particular, for 11 B-NCT treatment [24][25][26][27][28] ).…”

“…[29][30][31] We thus aimed on studying cation-receptor properties of halogen-containing iron(II) mono-and bis-clathrochelates (Scheme 1) having from two (FeBd 2 (Cl 2 Gm)(BF) 2 , FeBd 2 (Br 2 Gm)(BF) 2 , FeBd 2 (I 2 Gm) (BF) 2 , {FeBd 2 (BrGm)(BF) 2 } 2 and {FeBd 2 (IGm)(BF) 2 } 2 ) to six (Fe(Cl 2 Gm) 3 (Bn-C 4 H 9 ) 2 ) chlorine atoms in their chelate α-dioximate fragments. Note that these reactive compounds have been earlier recognized as convenient macrobicyclic precursors for their further functionalization with N,O,C,Snucleophiles [3,24,27,[29][30][31][32][33][34][35][36][37][38] (including those with ionophoric, pharmacophoric and fluorophoric groups), and for the design of hybride and multicentered compounds. [24,27,28] Here we also describe the cation-receptor properties of their dimethyl-and diamine-containing clathrochelate analogs FeBd 2 Dm(BF) 2 …”