Raman spectroscopy study of acid-base and structural properties of 9-[2-(phosphonomethoxy)ethyl]adenine in aqueous solutions.
The acid-base properties of the acyclic antiviral nucleotide analogue 9- [2-(phosphonomethoxy)ethyl] adenine (PMEA) in aqueous solutions are studied by means of Raman spectroscopy in a pH range of 1-11 and compared with the properties of its common adenosine monophosphate counterparts (5'-AMP, 3'-AMP, and 2'-AMP). Factor analysis is used to separate the spectra of pure ionic species (PMEA2-, HPMEA-, H2PMEA, H3PMEA+) in order to determine their abundance, sites of protonation, and corresponding spectroscopic pK(a) values. The characteristic Raman features of the neutral adenine moiety in PMEA2- and HPMEA- species resemble those of neutral adenine in the AMPs, whereas significant differences are observed between the Raman spectra of the N1-protonated adenine of the solute zwitterionic H2PMEA and its N1-protonated AMP counterparts. On the contrary, the spectrum of crystalline H2PMEA, adopting an "anti-like" conformation, is found to be similar to the N1-protonated AMPs in solution. To explain peculiar Raman features a "syn-like" conformation is suggested for N1-protonated PMEA species in aqueous solutions instead of an anti-like one adopted by H2PMEA in crystals or by common AMPs in aqueous solutions. A physical mechanism of the anti-like to syn-like conformational transition of the solute PMEA that is due to adenine protonation and the flexibility of the (phosphonomethoxy)ethyl group is proposed and discussed.
Kopecký
Vladimír
V
Institute of Physics, Charles University, Ke Karlovu 5, CZ-121 16 Prague 2, Czech Republic. kopecky@karlov.mff.cuni.cz
Mojzes
Peter
P
Burda
Jaroslav V
JV
Dostál
Lubomír
L
D000143:Acids / Q000737:chemistry*; D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D008956:Models, Chemical; D063065:Organophosphonates; D011487:Protein Conformation; D013059:Spectrum Analysis, Raman / Q000379:methods*
D000143:Acids; D063065:Organophosphonates; C053001:adefovir; D000225:Adenine