Eu(III) Macrocyclic Complexes Promote Cleavage of and Bind to Models for the 5‘-Cap of mRNA. Effect of Pendent Group and a Second Metal Ion

Abstract

The interaction of three Eu(III) macrocyclic complexes Eu(THED)3+, Eu(ATHC)3+, and Eu(ATHC)3+, and Eu(S-THP)3+ with two 5'-cap model compounds, GpppG and m7GpppG is studied (THED = 1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,-10-tetraazacyclododecane, ATHC = 1-(carbamoylmethyl)-4,7,10-tris(2-hydroxyethyl)-1,4,7,10- tetraazacyclododecane, S-THP = 1S,4S,7S,10S-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane). Laser-induced excitation luminescence spectroscopy is used to study the binding of Eu(S-THP)3+ to GpppG (K = 5.9 x 10(4) M-1) and to characterize the Eu(S-THP)-GpppG complex. Both Eu(THED)3+ and Eu(S-THP)3+ bind to m7GpppG as monitored by use of fluorescence spectroscopy with binding constants of 5.9 x 10(3) and 4.4 x 10(4) M-1, respectively. The kinetics of cleavage of GpppG by two macrocyclic complexes is studied. Cleavage of GpppG by Eu(THED)3+ is accelerated by 15-fold in the presence of an equivalent of Zn(NO3)2 at pH 7.3, 37 degrees C, suggesting that two metal ions accelerate the cap cleavage reaction. Eu(ATHC)3+ promotes cleavage of GpppG with a pseudo-first-order rate constant of 2.6 x 10(-5) s-1 at pH 7.3, 37 degrees C, and 0.30 mM complex.

Synthesis, spectroscopy, thermal and biological aspect of novel six‐coordinated dimeric iron(III) mixed‐ligand complexes

“…This band absolutely vanished in the spectra of mixed-ligand complexes, indicating deprotonation of carboxylic proton. The ν (C O) peak for A 5 , A 7 and A 8 was observed at ∼1680 cm −1 (cyclic) and ∼1660 cm −1 (acetyl), shifted to 1574 cm −1 on formation of mixed-ligand complexes. [23] These data are further supported by the ν (M-O) band's appearance at ∼510 cm −1 .…”

Lanthanide-Containing Molecular and Supramolecular Polymetallic Functional Assemblies

“…Among the plethora of applications involving lanthanide-containing edifices, [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] four fundamental metal-centered processes and functions can be recognized which intimately depend on the electronic structure: (1) electron transfer ability, (2) Lewis acidity, (3) optical properties (for light-emitting sensors), and (4) magnetic probes. The valence electrons of the neutral lanthanide elements Ln(0) are distributed in the 4f, 5d, and 6s orbitals, but the 4f electrons are deeply imbedded in the interior of the metal and the three valence electrons in the conduction band (two for Eu and Yb) of the metal originate preferentially from 5d and 6s orbitals.…”

“…The 4f electrons thus retain the fascinating magnetic and spectroscopic properties of the free ions which can be finely tuned in a predictable way via a close control of the metallic coordination sphere in the complexes. 1,25 Among a wealth of stimulating applications, the recent developments of (i) new phosphors for lighting, 26 (ii) high-efficiency electroluminescent devices for light-emitting diodes, 27 (iii) contrast agents for medical magnetic resonance imaging, 28 (iv) luminescent probes for analytes, 29 (v) labels for proteins and amino acids, 30 (vi) light-emitting sensors in fluoroimmunoassays, 31 (vii) tags for time-resolved luminescence microscopy, 32 (viii) magnetically addressable liquid crystals, 33 (ix) magnetic alloys for refrigeration, 34 (x) precursors for superconducting materials, 35 (xi) specific redox reagents for chemical transformation 36 or molecular-based information storage, 37 and (xii) acidic catalysts for sophisticated organic transformations 38,39 or for the cleavage of phosphodiester bridges in RNA 40 fully justify the efforts made to control the metallic sites and to selectively introduce lanthanides into organized assemblies. For more than two decades, systematic investigations of the subtle interplay between the structural control of the coordination sphere and the associated metal-centered electronic properties have led to the design of monometallic lanthanide-containing devices whose function can be judiciously addressed and tuned.…”

Monitoring proton dissociation and solution conformation of chiral ytterbium complexes with near‐IR CD

“…3 Neutral ligands such as THED (2) (1,4,7,10-tetrakis(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane) and (S)-THP (3) 1,4,7,10-tetrakis((S)-2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane (Scheme 1) were developed to give stable lanthanide complexes, endowed with good efficiency in phosphate ester transesterification/ hydrolysis 5,6 and RNA cleavage under mild conditions. 7 The interest in these complexes is oriented to build systems for the selective RNA cleavage, by linking the catalyst to an antisense sequence. 8 THP was recently indicated in development of alternative contrast agents: this is due to the exceptionally high water exchange rate measured with [Gd((S)-THP)(H 2 O)] 3+ , 9 and to the tendency of these systems to give supramolecular adducts.…”