Synthesis, physicochemical properties, and biological evaluation of hydroxypyranones and hydroxypyridinones: novel bidentate ligands for cell-labeling.
The synthesis of a range of hydroxypyranones and hydroxypyridinones with potential for the chelation of indium(III) is described. The crystal structures of two of the indium complexes are presented. The distribution coefficients of the ligands and the corresponding iron(III), gallium(III), and indium(III) complexes are reported. Good linear relationships between the distribution coefficients of the iron and gallium complexes and iron and indium complexes were obtained. In contrast a nonlinear relationship was obtained between the distribution coefficient of the free ligand and the distribution coefficient of the three groups of complexes. This latter relationship was used to identify compounds with optimal cell labeling properties. Two such compounds both 6-(alkoxymethyl)-3-hydroxy-4H-pyran-4-ones have been compared with tropolone for their ability to label human leucocytes with 111In. The leucocyte labeling efficiencies of the selected ligands were greater and the in-vitro plasma stabilities were similar to that of 111In-tropolonate. These results suggest that the new bidentate ligands may offer advantages over those currently used for cell-labeling.
Ellis
B L
BL
Department of Pharmacy, King's College London, U.K.
Duhme
A K
AK
Hider
R C
RC
Hossain
M B
MB
Rizvi
S
S
van der Helm
D
D
D002477:Cells / Q000378:metabolism*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D004355:Drug Stability; D004912:Erythrocytes / Q000378:metabolism; D005708:Gallium / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007205:Indium Radioisotopes / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000378:metabolism; D011728:Pyridones / Q000138:chemical synthesis* / Q000378:metabolism; D011753:Pyrones / Q000138:chemical synthesis / Q000378:metabolism
C101605:2-(n-butoxymethyl)-5-hydroxy-4H-pyran-4-one; C101604:5-hydroxy-2-(n-propoxymethyl)-4H-pyran-4-one; D007205:Indium Radioisotopes; D008024:Ligands; D011714:Pyrans; D011728:Pyridones; D011753:Pyrones; D005708:Gallium; D007501:Iron