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A combined parallel synthesis and screening of macrocyclic lanthanide complexes for the cleavage of phospho di- and triesters and double-stranded DNA

Academic Article
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Overview

authors

  • Berg, T.
  • Simeonov, A.
  • Janda, Kim

publication date

  • January 1999

journal

  • Journal of Combinatorial Chemistry  Journal

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 (K(m) = 7.4 microM, kcat = 4.5 x 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.

subject areas

  • Catalysis
  • Combinatorial Chemistry Techniques
  • DNA
  • Esters
  • Hydrolysis
  • Kinetics
  • Metals, Rare Earth
  • Phosphates
  • Substrate Specificity
  • Time Factors
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Identity

International Standard Serial Number (ISSN)

  • 1520-4766

Digital Object Identifier (DOI)

  • 10.1021/cc9800125

PubMed ID

  • 10746017
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Additional Document Info

start page

  • 96

end page

  • 100

volume

  • 1

issue

  • 1

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