Adsorption of 6-mercaptopurine and 6-mercaptopurine-ribosideon silver colloid: a pH-dependent surface-enhanced Raman spectroscopy and density functional theory study. II. 6-mercaptopurine-riboside.
Surface-enhanced Raman spectroscopy (SERS) has been applied to characterize the interaction of 6-mercaptopurine-ribose (6MPR), an active drug used in chemotherapy of acute lymphoblastic leukemia, with a model biological substrate at therapeutic concentrations and as function of the pH value. Therefore, a detailed vibrational analysis of crystalline and solvated (6MPR) based on Density Functional Theory (DFT) calculations of the thion and thiol tautomers has been performed. 6MPR adopts the thion tautomeric form in the polycrystalline state. The SERS spectra of 6MPR and 6-mercaptopurine (6MP) recorded on silver colloid provided evidence that the ribose derivative shows different adsorption behavior compared with the free base. Under acidic conditions, the adsorption of 6MPR on the metal surface via the N7 and possibly S atoms was proposed to have a perpendicular orientation, while 6MP is probably adsorbed through the N9 and N3 atoms. Under basic conditions both molecules are adsorbed through the N1 and possibly S atoms, but 6MP has a more tilted orientation on the silver colloidal surface while 6MPR adopts a perpendicular orientation. The reorientation of the 6MPR molecule on the surface starts at pH 8 while in the case of 6MP the reorientation starts around pH 6. Under basic conditions, the presence of the anionic molecular species for both molecules is suggested. The deprotonation of 6MP is completed at pH 8 while the deprotonation of the riboside is finished at pH 10. For low drug concentrations under neutral conditions and for pH values 8 and 9, 6MPR interacts with the substrate through both N7 and N1 atoms, possibly forming two differently adsorbed species, while for 6MP only one species adsorbed via N1 was evidenced.
Szeghalmi
A V
AV
Institute of Physical Chemistry, University of Wuerzburg, Am Hubland, D-97074, Wuerzburg, Germany.
Leopold
L
L
Pînzaru
S
S
Chis
V
V
Silaghi-Dumitrescu
I
I
Schmitt
M
M
Popp
J
J
Kiefer
W
W
D000327:Adsorption; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry*; D003102:Colloids; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015122:Mercaptopurine / Q000737:chemistry*; D015394:Molecular Structure; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D012834:Silver; D013059:Spectrum Analysis, Raman / Q000379:methods; D013868:Thioinosine / Q000737:chemistry*
D000964:Antimetabolites, Antineoplastic; D003102:Colloids; D012834:Silver; D013868:Thioinosine; D015122:Mercaptopurine