Ca. Blindauer et al., MAGNESIUM COMPLEXES OF THE ANTIVIRAL 9-[2-(PHOSPHONOMETHOXY)ETHYL]ADENINE (PMEA) AND OF ITS 1-DEAZA, 3-DEAZA, AND 7-DEAZA ANALOGS IN AQUEOUS-SOLUTION, JBIC. Journal of biological inorganic chemistry, 3(4), 1998, pp. 423-433
The stability constants of the 1:1 complexes formed between Mg2+ and t
he anions of the N1, N3, and N7 deaza derivatives of 9-[2-(phosphonome
thoxy)ethyl]adenine (PA(2-)), i.e., of Mg(H;PA)(+) and Mg(PA), were de
termined by potentiometric pH titration in aqueous solution (25 degree
s C; I=0.1 M, NaNO3) and compared with previous results [Sigel H, et a
l. (1992) Helv Chim Acta 75.2634-2656], obtained under the same condit
ions, for the corresponding complexes of 9-[2-(phosphonomethoxy)ethyl]
adenine (PMEA(2-)) and (phosphonomethoxy)ethane (PME2-). Based on the
analysis of a microconstant scheme it is concluded that in the monopro
tonated complexes, Mg(H;PA)(+), Mg2+ is coordinated to a significant p
art at the nucleobase, H+ being at the phosphonate group. By making us
e of logK(Mg(R-PO3))(Mg) versus pK(H(R-PO3))(H) straight-line plots (a
lso obtained previously; see above) for simple phosphonates and phosph
ate monoesters, it is shown that all the Mg(PA) complexes, including t
hose with PMEA(2-) and PME2-, are more stable than expected on the bas
is of the basicity of the -PO32- group. This proves that, to some exte
nt, five-membered chelates, Mg(PA)(cl/O), involving the ether oxygen o
f the -CH2-O-CH2-PO32- chain are formed; their formation degree amount
s to about 30-40% in equilibrium with the isomer having only a phosnho
nate-Mg2+ coordination. In the case of Mg(1-deaza-PMEA), probably a fu
rther isomer occurs in which also N3 of the nucleobase participates. T
he different properties between the Mg(PA) species and the Mg(AMP) com
plex are discussed.