annual report annual report annual report annual report 2005

72
RADIOCHEMISTRY, STABLE ISOTOPES,
NUCLEAR ANALYTICAL METHODS, GENERAL CHEMISTRY
last years [1]. These thermodynamically stable and
kinetically inert 99m Tc chelates are good candidates
for radiopharmaceuticals or their precursors. Due
to the softness (HSAB) of the technetium(I) centre,
chelators with soft donor atoms are preferred
as the ligands. Widely studied in this respect are
bi- and tridentate derivatives of pyridine and/or
imidazole (aromatic N donors) in combination with
other donor atoms, in particular sulphur. The aim
of the present work is to select ligands that form
very stable tricarbonyl complexes of technetium(I),
and after further functionalization can be precursors
for radiopharmaceuticals of the second generation.
Two kinds of [Tc(CO) 3 LB] complexes were obtained
and studied, where L is a neutral chelating
ligand with either N,S donor atoms, N-methyl-2-pyridinecarbothioamide,
L NS , or its analog with N,O
donor atoms, N-methyl-2-pyridinecarboamide,
L NO
, while B is a monovalent anion or H 2
O. The
complexes were prepared both with 99m Tc at n.c.a.
level (B=OH – or H 2 O) and with 99 Tc in mg quantities
(B=Cl – ). The 99m Tc complexes were investigated
by HPLC and those of 99 Tc – by IR measurements.
Na[ 99m TcO 4
] was eluted from a 99 Mo/ 99m Tc generator
using 0.9% saline. Synthesis of precursor 1
in water was carried out according to Alberto’s
low-pressure method [2,3] and/or by using potassium
boranocarbonate [4]. The complexes in n.c.a
concentrations were obtained from 1 by adding a
methanol solution of L to the precursor solution
in a phosphate-buffered saline (PBS) to reach
[L]=10 –3 M, followed by heating the mixture at 37
or 75 o C for 10-60 min. The complexes of 99 Tc were
prepared in water-methanol solution by adding
little excess of the ligand to the precursor solution
and heating the mixture at 50 o C, then recrystallized
from a mixture of dichloromethane-hexane.
The IR spectra were carried out in KBr pellets
using a Perkin Elmer 16 PC FT-IR spectrophotometer.
Fig.1. IR spectrum of [Tc(CO) 3 L NS Cl]; L NS =N-methyl-2-pyridinecarbothioamide.
We expect that each ligand coordinates the
metal center bidently via the pyridine nitrogen and
the X atom (X=O or S), forming a five-membered
Fig.2. IR spectrum of [Tc(CO) 3 L NO Cl] (contaminated with
some L NO ); L NO =N-methyl-2-pyridinecarboamide.
chelate ring. This conclusion is supported by the similarity
of IR spectra of the 99 Tc complexes studied
(Figs.1 and 2) to those of their rhenium analogs
[5,6]. Two characteristic peaks of CO vibrations
(2026 and 1928 cm –1 ) confirm the existence of the
99
Tc(CO) 3
core in the complexes studied.
The yield of the [ 99m Tc(CO) 3 L NX B] complexes
(B=H 2 O and/or OH – ) was studied by HPLC [7].
After 40 min incubation at 75 o C, the [ 99m Tc(CO) 3
L NS
B]
complex was obtained with the nearly 100% yield
(Fig.3), while the yield of [ 99m Tc(CO) 3 L NO B] was
lower (53 to 84% depending on pH of the complex
formation, Fig.4). Two forms of the complexes
were observed: cationic (B=H 2 O), eluted as the
peak No.2 on the chromatograms (Figs.3 and 4),
and neutral (B=OH – ), eluted as the peak No.3.
The equilibrium between these two forms depended
on the complex and on pH of the complex
formation. It was shifted to over 90% of the neutral
form at pH>7 for [ 99m Tc(CO) 3 L NS B] (Fig.3),
but for [ 99m Tc(CO) 3 L NO B] the cationic form predominated
(from 50% at pH 3 to 64% at pH 10
(Fig.4). The coexistence of the two forms of the
complexes, cationic and neutral, was also confirmed
by paper electrophoresis. Under the appropriate
experimental conditions (e.g. proper pH)
two 99m Tc peaks appeared on the electropherograms:
that remaining at the starting point corresponded
to the neutral form, while that moving to
the cathode corresponded to the cationic form.
The easier hydrolysis of the [ 99m Tc(CO) 3 L NS H 2 O] +
complex can hardly be discussed in terms of easier
deprotonation of the H 2 O molecule coordinated
to the technetium atom more strongly than in the
analogous [ 99m Tc(CO) 3 L NO H 2 O] + complex. The
stronger coordination of the L NS than L NO ligand
reflected by the greater yield (and stability) of the
former complex, and the smaller positive charge
on the technetium atom calculated for the former
(0.14 e) than for the latter (0.31 e) [8] lead to the
conclusion on the weaker bonding of the H 2 O molecule
in the former species. Therefore, the hydrolysis
proceeds most probably via the ligand exchange,
i.e. the exchange of the coordinated H 2 O molecule
for an OH – ion from the aqueous solution.