Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)
The result's identifiers
Result code in 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>
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)
Original language description
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.
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
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
New Journal of Chemistry
ISSN
1144-0546
e-ISSN
1369-9261
Volume of the periodical
46
Issue of the periodical within the volume
14
Country of publishing house
GB - UNITED KINGDOM
Number of pages
10
Pages from-to
6484-6493
UT code for WoS article
000769618200001
EID of the result in the Scopus database
2-s2.0-85127711024