A Combined Parallel Synthesis and Screening of Macrocyclic Lanthanide Complexes for the Cleavage of Phospho Di- and Triesters and Double-Stranded DNA
- 18 December 1998
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Combinatorial Chemistry
- Vol. 1 (1) , 96-100
- https://doi.org/10.1021/cc9800125
Abstract
A parallel synthesis of macrocyclic lanthanide−ligand complexes 4Ln has been developed in conjunction with a parallel screening of these ligands for catalysis of phosphate ester hydrolysis. Complexes 4Ln were screened on a 96-well plate reader for their ability to catalyze the hydrolysis of a variety of phosphate esters efficiently. The hydrolysis of bis(4-nitrophenyl) phosphate (BNPP) 5 and p-nitrophenylethyl phosphate 6 was accelerated by up to 150-fold in the presence of the complex 4cGd. The cleavage of a double-stranded DNA plasmid with this same complex obeyed saturation kinetics following a Michaelian model (Km = 7.4 μM, kcat = 4.5 × 10-3 min-1). Our findings demonstrate how a combination of parallel synthesis and screening can expedite compound access, accelerate catalyst identification, and thereby dramatically increase the speed of finding good ligand−metal combinations.Keywords
This publication has 36 references indexed in Scilit:
- Efficient Catalytic Phosphate Diester Cleavage by the Synergetic Action of Two Cu(II) Centers in a Dinuclear Cis-Diaqua Cu(II) Calix[4]arene Enzyme ModelJournal of the American Chemical Society, 1998
- Rapid and Highly Selective Cleavage of Ribonucleoside 2′,3′-Cyclic Monophosphates by Dinuclear CuII ComplexesAngewandte Chemie International Edition in English, 1997
- Minimized protein still binds antibodyChemical & Engineering News, 1996
- A General Solid-Phase Synthesis Strategy for the Preparation of 2-Pyrrolidinemethanol LigandsThe Journal of Organic Chemistry, 1995
- Phosphatase Catalysis Developed via Combinatorial Organic ChemistryThe Journal of Organic Chemistry, 1995
- Rapid Hydrolysis of RNA with a CuII ComplexAngewandte Chemie International Edition in English, 1995
- RNA Cleavage and Phosphate Diester Transesterification by Encapsulated Lanthanide Ions: Traversing the Lanthanide Series with Lanthanum(III), Europium(III), and Lutetium(III) Complexes of1,4,7,10-Tetrakis(2-hydroxyalkyl)-1,4,7,10-tetraazacyclododecaneInorganic Chemistry, 1994
- Lanthanide(III) Tetraamide Macrocyclic Complexes as Synthetic Ribonucleases: Structure and Catalytic Properties of [La(tcmc)(CF3SO3)(EtOH)](CF3SO3)2Angewandte Chemie International Edition in English, 1994
- Transesterification of a phosphate diester by divalent and trivalent metal ionsInorganic Chemistry, 1992
- Hydrolysis of phosphodiesters with nickel(II), copper(II), zinc(II), palladium(II), and platinum(II) complexesInorganic Chemistry, 1990