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Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA)
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SYSNO ASEP 0556558 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Acid-base properties of an antivirally active acyclic nucleoside phosphonate: (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) Tvůrce(i) Blindauer, C. A. (CH)
Holý, Antonín (UOCHB-X)
Sigel, A. (CH)
Operschall, B. P. (CH)
Griesser, R. (CH)
Sigel, H. (CH)Zdroj.dok. New Journal of Chemistry. - : Royal Society of Chemistry - ISSN 1144-0546
Roč. 46, č. 14 (2022), s. 6484-6493Poč.str. 10 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova metal-ion complexes ; adenosine 5-monophosphate AMP ; nucleotide analogs Obor OECD Organic chemistry Způsob publikování Open access Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000769618200001 EID SCOPUS 85127711024 DOI 10.1039/d2nj00543c Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2023 Elektronická adresa https://doi.org/10.1039/D2NJ00543C
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