Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F22%3A00556558" target="_blank" >RIV/61388963:_____/22:00556558 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1039/D2NJ00543C" target="_blank" >https://doi.org/10.1039/D2NJ00543C</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/d2nj00543c" target="_blank" >10.1039/d2nj00543c</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)

Popis výsledku v původním jazyce

HPMPA is an acyclic nucleoside phosphonate analogue of AMP which displays antiviral properties. Therefore, its acid-base behavior as well as that of related compounds like PMEA, 9-[2-(phosphonomethoxy)ethyl]adenine, are for many reasons (e.g., binding to enzymes, coordination of metal ions) of general interest. HPMPA can accept two protons at the phosphonate and two more at the adenine residue, but not all acidity constants are accessible by potentiometric pH titrations. Therefore, we measured the chemical shifts of the nine non-exchangeable HPMPA protons by H-1 NMR in D2O in dependence on pD in the range from 1 to 12. The corresponding results allowed identifying the protonation sites and, transferred to aqueous solution, they gave also the acidity constants. The most basic site is the phosphonate group followed by N1 of adenine. The pK(a) values increase from ca.0.27 [-N7(H)(+)] via 1.27 [-PO(OH)(2)] and 4.23 [-N1(H)(+)] to 6.86 [-PO(OH)(-)]. In the fully protonated species charge repulsion exists between N1(H)(+) and N7(H)(+), therefore, the affinity of N7 for H+ is not correctly reflected by the measured acidity constant (ca.0.27). Needed is the intrinsic micro acidity constant which reflects the H+ affinity of N7 under conditions where N1 is unprotonated, we abbreviate this species as H+center dot N7(HPMPA)N1. The corresponding microconstant is estimated to be pk(H center dot N7-N1)(N7-N1) approximate to 3.5, the minor species H+center dot N7(HPMPA)N1 occurs with an estimated formation degree between about 5 to 20%. The basicity of the adenine nitrogens decreases in the order N1 > N7 > N3.

Název v anglickém jazyce

Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)

Popis výsledku anglicky

HPMPA is an acyclic nucleoside phosphonate analogue of AMP which displays antiviral properties. Therefore, its acid-base behavior as well as that of related compounds like PMEA, 9-[2-(phosphonomethoxy)ethyl]adenine, are for many reasons (e.g., binding to enzymes, coordination of metal ions) of general interest. HPMPA can accept two protons at the phosphonate and two more at the adenine residue, but not all acidity constants are accessible by potentiometric pH titrations. Therefore, we measured the chemical shifts of the nine non-exchangeable HPMPA protons by H-1 NMR in D2O in dependence on pD in the range from 1 to 12. The corresponding results allowed identifying the protonation sites and, transferred to aqueous solution, they gave also the acidity constants. The most basic site is the phosphonate group followed by N1 of adenine. The pK(a) values increase from ca.0.27 [-N7(H)(+)] via 1.27 [-PO(OH)(2)] and 4.23 [-N1(H)(+)] to 6.86 [-PO(OH)(-)]. In the fully protonated species charge repulsion exists between N1(H)(+) and N7(H)(+), therefore, the affinity of N7 for H+ is not correctly reflected by the measured acidity constant (ca.0.27). Needed is the intrinsic micro acidity constant which reflects the H+ affinity of N7 under conditions where N1 is unprotonated, we abbreviate this species as H+center dot N7(HPMPA)N1. The corresponding microconstant is estimated to be pk(H center dot N7-N1)(N7-N1) approximate to 3.5, the minor species H+center dot N7(HPMPA)N1 occurs with an estimated formation degree between about 5 to 20%. The basicity of the adenine nitrogens decreases in the order N1 > N7 > N3.

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

2022

Kód důvěrnosti údajů

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

Název periodika

New Journal of Chemistry

ISSN

1144-0546

e-ISSN

1369-9261

Svazek periodika

46

Číslo periodika v rámci svazku

14

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

10

Strana od-do

6484-6493

Kód UT WoS článku

000769618200001

EID výsledku v databázi Scopus

2-s2.0-85127711024