BIBLIOS

Document type
Journal articles

Document subtype
Full paper

Title
A novel V(IV)O-pyrimidinone complex: synthesis, solution speciation and human serum protein binding

Participants in the publication
Gisela Gonçalves (Author)
M. Margarida C.A. Castro (Author)
Fernando Avecilla (Author)
Tamás Kiss (Author)
Tamás Jakusch (Author)
Isabel Tomaz (Author)
Dep. Química e Bioquímica
CQE
Isabel Correia (Author)
Luís F. Veiros (Author)
Lorena Palacio (Author)
Miguel Maestro (Author)
M. Helena V. Garcia (Author)
Dep. Química e Bioquímica
João Costa Pessoa (Author)

Summary
The pyrimidinones mhcpe, 2-methyl-3H-5-hydroxy-6-carboxy-4-pyrimidinone ethyl ester (mhcpe, 1), 2,3-dimethyl-5-benzyloxy-6-carboxy-4-pyrimidinone ethyl ester (dbcpe, 2) and N-methyl-2,3-dimethyl-5-hydroxy-6-carboxyamido-4-pyrimidinone (N-MeHOPY, 3), are synthesized and their structures determined by single crystal X-ray diffraction. The acid–base properties of 1 are studied by potentiometric and spectrophotometric methods, the pKa values being 1.14 and 6.35. DFT calculations were carried out to determine the most stable structure for each of the H2L+, HL and L− forms (HL = mhcpe) and assign the groups involved in the protonation–deprotonation processes. The mhcpe− ligand forms stable complexes with V(IV)O2+ in the pH range 2 to 10, and potentiometry, EPR and UV-Vis techniques are used to identify and characterize the V(IV)O–mhcpe species formed. The results are consistent with the formation of V(IV)O, (V(IV)O)L, (V(IV)O)L2, (V(IV)O)2L2H−2, (V(IV)O)L2H−1, (V(IV)O)2L2H−3, (V(IV)O)LH−2 species and V(IV)O-hydrolysis products. Calculations indicate that the global binding ability of mhcpe towards V(IV)O(2+) is similar to that of maltol (Hmaltol = 3-hydroxy-2-methyl-4H-pyran-4-one) and lower than that of 1,2-dimethyl-3-hydroxy-4-pyridinone (Hdhp). The interaction of V(IV)O-complexes with human plasma proteins (transferrin and albumin) is studied by circular dichroism (CD), EPR and 51V NMR spectroscopy. V(IV)O–mhcpe–protein ternary complexes are formed in both cases. The binding of V(IV)O(2+) to transferrin (hTF) in the presence of mhcpe involves mainly [(V(IV)O)1(hTF)(mhcpe)1], [(V(IV)O)2(hTF)(mhcpe)1] and [[V(IV)O)2(hTF)(mhcpe)2] species, bound at the Fe(III) binding sites, and the corresponding conditional formation constants are determined. Under the conditions expected to prevail in human blood serum, CD data indicate that the V(IV)O–mhcpe complexes mainly bind to hTF; the formation of V(IV)O–hTF–mhcpe complexes occurs in the presence of FeIII as well, distinct EPR signals being clearly obtained for Fe(III)–hTF and to V(IV)O–hTF–mhcpe species. Thus this study indicates that transferrin plays the major role in the transport of V(IV)O–mhcpe complexes under blood plasma conditions in the form of ternary V(IV)–ligand–protein complexes.


Where published
JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS

Publication Identifiers
ISSN - 1472-7773



Document Identifiers
URL - http://dx.doi.org/10.1039/c3dt50553g
DOI - https://doi.org/10.1039/c3dt50553g