Glycine–alanine conjugated macrocyclic lanthanide ion complexes as artificial ribonucleases

The lanthanide ion based macrocyclic complexes 1La, 1Eu and 1Yb, were synthesised by the alkylation of L-alanine derived α-chloroamide, giving a tetrasubstituted GlyAla conjugated azamacrocycle using a 1,4,7,10-tetraazacyclododecane, followed by a complexation with either La(III), Eu(III) or Yb(III) triflate. Each complex gave rise to enhancements in the rate of hydrolysis of the phosphodiester of HPNP, an RNA mimic compound, at pH 7.4 and 37°C. For 1La, the hydrolysis was shown to give dual pH behaviour, where within a narrow pH window the hydrolysis of HPNP was greatly enhanced between 6.5 and 7.0, whereas it decreased between 7.2 and 7.4. At higher pH, above 8, the rate was again greatly enhanced. We conclude that these enhancements are due to the formation of a hydrophobic cavity in 1 upon lanthanide ion complexation, in conjunction with the Lewis acid activation of the phosphate diester by the metal ion. These complexes thus mimic the nature of the active site of many ribonucleases.