Metal Ion-Coordinating Properties in Aqueous Solutions of the Antivirally Active Nucleotide Analogue (S)-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) - Quantification of Complex Isomeric Equilibria

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00509500" target="_blank" >RIV/61388963:_____/19:00509500 - isvavai.cz</a>

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/abs/10.1002/ejic.201900620" target="_blank" >https://onlinelibrary.wiley.com/doi/abs/10.1002/ejic.201900620</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ejic.201900620" target="_blank" >10.1002/ejic.201900620</a>

Result language

angličtina

Original language name

Metal Ion-Coordinating Properties in Aqueous Solutions of the Antivirally Active Nucleotide Analogue (S)-9-[3-Hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) - Quantification of Complex Isomeric Equilibria

Original language description

Acyclic nucleoside phosphonates are of medical relevance and deserve detailed chemical characterization. We focus here on (S)‐9‐[3‐hydroxy‐2‐(phosphonomethoxy)propyl]adenine (HPMPA) and include for comparison 9‐[2‐(phosphonomethoxy)ethyl]adenine (PMEA), as well as the nucleobase‐free (phosphonomethoxy)ethane (PME) and (R)‐hydroxy‐2‐(phosphonomethoxy)propane (HPMP). The acidity constants of H3(HPMPA)+ were determined and compared with those of the related phosph(on)ate derivatives, they are also needed to understand the properties of the metal ion complexes. Given that in vivo nucleotides and their analogues participate in reactions typically as divalent metal ion (M2+) complexes, the stability constants of the M(H,HPMPA)+ and M(HPMPA) species with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured. Comparisons between the results for HPMPA2– and the previous data for PMEA2–, HPMP2– and PME2– revealed that for most M(HPMPA) complexes the enhanced stability (the enhancement relative to the stability of a simple phosphonate‐M2+ coordination), can solely be explained by the formation of 5‐membered chelates involving the ether oxygen. These chelates occur in equilibrium with simple ′open′ phosphonate‐M2+ species, the phosphonate group being the primary binding site. The only exceptions are the M(HPMPA) complexes of Ni2+, Cu2+, and Zn2+, which show an additional stability enhancement, in these instances not only the indicated 5‐membered chelates are formed, but M2+ coordinates in addition to N3 of the adenine residue forming a 7‐membered chelate ring. This observation regarding N3 is important because it emphasizes the metal ion affinity of this site (which is often ignored). Note that in the DNA double helix N3 is exposed to the solvent in the minor groove. The stability data for the monoprotonated M(H,HPMPA)+ complexes suggest that these carry H+ at the phosphonate group whereas M2+ is partly at the nucleobase and partly also at the phosphonate group. The ratios of these isomers depend on the metal ion involved, e.g., for Cu(H,HPMPA) the ratio of the isomers is about 1:1.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

European Journal of Inorganic Chemistry

ISSN

1434-1948

e-ISSN

—

Volume of the periodical

2019

Issue of the periodical within the volume

35

Country of publishing house

DE - GERMANY

Number of pages

12

Pages from-to

3892-3903

UT code for WoS article

000485476700001

EID of the result in the Scopus database

2-s2.0-85074199210