Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Metal-ion binding properties of (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC, Cidofovir). A nucleotide analogue with activity against DNA viruses

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10401 - Organic chemistry

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

Inorganica chimica acta

ISSN

0020-1693

e-ISSN

—

Svazek periodika

472

Číslo periodika v rámci svazku

Mar 1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

283-294

Kód UT WoS článku

000424293700030

EID výsledku v databázi Scopus

2-s2.0-85026285584