title: Carbohydrate-appended 3-hydroxy-4-pyridinone complexes of the [M(CO)3]+ core (M = Re, 99mTc, 186Re).
abstract: This work describes the use of 3-hydroxy-4-pyridinone ligands for binding the [M(CO)(3)](+) core (M = Re, Tc) in the context of preparing novel Tc(I) and Re(I) glucose conjugates. Five pyridinone ligands bearing pendent carbohydrate moieties, HL(1-5), were coordinated to the [M(CO)(3)](+) core on the macroscopic scale (M = Re) and on the tracer scale (M = (99m)Tc, (186)Re). On the macroscopic scale the complexes, ReL(1-5)(CO)(3)(H(2)O), were thoroughly characterized by mass spectrometry, IR spectroscopy, UV-visible spectroscopy, elemental analysis, and 1D/2D NMR spectroscopy. Characterization confirmed the bidentate coordination of the pyridinone and the pendent nature of the carbohydrate and suggests the presence of a water molecule in the sixth coordination site. In preliminary biological evaluation, both the ligands and complexes were assessed as potential substrates or inhibitors of hexokinase, but showed no activity. Labeling via the [(99m)Tc(CO)(3)(H(2)O)(3)](+) precursor gave the tracer species (99m)TcL(1-5)(CO)(3)(H(2)O) in high radiochemical yields. Similar high radiochemical yields when labeling with (186)Re were facilitated by in situ preparation of the [(186)Re(CO)(3)(H(2)O)(3)](+) species in the presence of HL(1-5) to give (186)ReL(1-5)(CO)(3)(H(2)O). Stability challenges, incubating (99m)TcL(1-5)(CO)(3)(H(2)O) in the presence of excess cysteine and histidine, confirmed complex stability up to 24 h.
authors.affiliation: Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Cara L
authors.initials: CL
authors.lastname: Ferreira
authors.forename: Simon R
authors.initials: SR
authors.lastname: Bayly
authors.forename: David E
authors.initials: DE
authors.lastname: Green
authors.forename: Tim
authors.initials: T
authors.lastname: Storr
authors.forename: Cheri A
authors.initials: CA
authors.lastname: Barta
authors.forename: Jennifer
authors.initials: J
authors.lastname: Steele
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Adam
authors.forename: Chris
authors.initials: C
authors.lastname: Orvig
mesh_terms: D002241:Carbohydrates / Q000737:chemistry*; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry*; D011868:Radioisotopes / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D013667:Technetium / Q000737:chemistry*
chemical_list: D002241:Carbohydrates; D007502:Iron Chelating Agents; D008024:Ligands; D011728:Pyridones; D011868:Radioisotopes; C020366:3-hydroxy-4-pyridone; D012211:Rhenium; D013667:Technetium; D006593:Hexokinase; D005947:Glucose