Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F18%3A00489564" target="_blank" >RIV/61388963:_____/18:00489564 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.ica.2017.06.011" target="_blank" >http://dx.doi.org/10.1016/j.ica.2017.06.011</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.ica.2017.06.011" target="_blank" >10.1016/j.ica.2017.06.011</a>
Alternative languages
Result language
angličtina
Original language name
Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses
Original language description
The acyclic nucleoside phosphonate (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir) has been approved for clinical use in antiviral therapy. We determined the acidity constants of H-2(HPMPC)(+/-), as well as that of the nucleobase-free (hydroxy-2-(phosphonomethoxy)propane (H(HPMP)(-)) (I = 0.1 M, NaNO3, 25 degrees C). Given that in vivo nucleotides and their analogues participate in reactions typically as metal ion (M2+) complexes, the stability constants of the M(H,HPMPC)(+), M(HPMPC), and M(HPMP) complexes with M2+ = Mg2+, Ca2+, Sr2+, Ba2+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+ were measured. Comparisons between results for HPMP2- and previous data for PME2- (CH3CH2-O-CH2PO32-, phosphonomethoxyethane) revealed the hydroxyl-group effect. The hydroxyl group stabilizes only complexes with the heavier alkaline earth metal ions (Ca2+, Sr2+, Ba2+). For all other complexes, the enhanced stability can solely be explained by the formation of 5-membered chelates involving the ether oxygen, these occur in equilibrium with simple 'open' phosphonate-M2+ species. The stability of the M(HPMPC) complexes is also higher than expected for a phosphonate-only coordination, indicating that chelates are formed, but comparison with the HPMP2- data shows that the cytosine base does not affect complex stability. Similar observations were made previously with related cytosine derivatives. The stability data for the monoprotonated M(H,HPMPC)(+) complexes suggest that these carry H+ predominantly on the phosphonate group, and M2+ on the nucleobase.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - 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
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Inorganica chimica acta
ISSN
0020-1693
e-ISSN
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Volume of the periodical
472
Issue of the periodical within the volume
Mar 1
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
12
Pages from-to
283-294
UT code for WoS article
000424293700030
EID of the result in the Scopus database
2-s2.0-85026285584