Triaza-macrocyclic complexes of aluminium, gallium and indium halides: Fast 18F and 19F incorporation via halide exchange under mild conditions in aqueous solution

Article abstract of DOI:10.1039/c3sc52104d

Rapid and complete fluorination of the complexes [MCl₃(L)] (L = Me₃-tacn, BzMe₂-tacn, M = Al, Ga, In) occurs at room temperature via reaction of a MeCN solution of the complex with 3 mol equiv. of KF in water. The Ga and I

Full text of DOI:10.1039/c3sc52104d

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Triaza-macrocyclic complexes of aluminium,
18
19
gallium and indium halides: fast F and F
incorporation via halide exchange under mild
conditions in aqueous solution†
Cite this: Chem. Sci., 2014, 5, 381
Rajiv Bhalla,ab Christine Darby,c William Levason,c Sajinder K. Luthra,a
a
c
Graeme McRobbie, Gillian Reid, George Sandersonc and Wenjian Zhangc
*
Rapid and complete fluorination of the complexes [MCl3(L)] (L ¼ Me3-tacn, BzMe2-tacn, M ¼ Al, Ga, In)
occurs at room temperature via reaction of a MeCN solution of the complex with 3 mol equiv. of KF in
water. The Ga and In complexes are also readily fluorinated using R4NF (R ¼ Me or nBu) in MeCN
solution, whereas no reaction occurs with the Al species under these conditions. The distorted
octahedral fac-trifluoride coordination at M is confirmed in solution by multinuclear (19F, 27Al, 71Ga and
115In) NMR spectroscopic studies, leading to sharp resonances with 19F–71Ga and 19F–115In couplings
evident. The [MF3(L)] are extremely stable in aqueous solution and at low pH; they crystallise as
tetrahydrates, [MF3(Me3-tacn)]$4H2O, with extended H-bonding networks formed through both F/H–O
and O/H–O contacts. [InF3(BzMe2-tacn)]$1.2H2O also shows intermolecular F/H–O hydrogen bonding
contacts. The prospects for developing this coordination chemistry further to take advantage of the high
metal–fluoride bond energies to enable rapid, late-stage fluorination of large macromolecules under
mild conditions for PET imaging applications in nuclear medicine are discussed. This work also
demonstrates that F-18 radiolabelling to form [F-18] [GaF3(BzMe2-tacn)] is effected readily at room
temperature in aqueous MeCN over 30–60 min on addition of 2.99 mol equiv. of [19F]–KFaq and 0.4 mL
Received 26th July 2013
Accepted 24th October 2013
DOI: 10.1039/c3sc52104d
www.rsc.org/chemicalscience
[
18F]–KFaq (100–500 MBq) to [GaCl3(BzMe2-tacn)] with ca. 30% incorporation.
preferably in the nal step). Rapid, late-stage uorination of
Introduction
complex molecules is consequently important for the develop-
ment of new candidates for PET imaging in nuclear medicine.
There has been a signicant research effort in this area to
provide routes for C–F bond formation reactions, as alternatives
to the traditional nucleophilic reactions. Notable successes
include the use of electrophilic ‘F+’ and metal-catalysed
processes, as reported by Ritter, Groves, Buchwald and
others.2–5 There is also a need to develop F-18 labelling methods
which permit radiouorination under mild conditions (neutral
pH, room temperature) since this will improve the compatibility
of the labelling conditions with a diverse range of biomolecules.
Recent efforts towards boron-based agents for F-18 capture
The increased availability of radioisotopes of the main group
metals for radiopharmaceutical applications in imaging and
therapy (e.g. 67Ga, 68Ga, 111In, 113mIn, 117mSn) has driven the
development of new coordination chemistry with specic
ligand types.1 Fluorine-18 is the radioisotope of choice for
medical applications using (non-invasive) PET imaging, owing
to its ease of production via cyclotrons that are now widely
available, and its short half-life (t1/2 ¼ 109.8 minutes). For
radioisotopes with a relative short half-life, there is a drive to
introduce the radiolabel in the late stage of the synthesis (and
6
7
8
¨
include the work of Perrin, Gabbaı and Tsien.
aGE Healthcare UK, White Lion Road, Amersham, HP7 9LL, UK
bCentre for Advanced Imaging, University of Queensland, Brisbane, Queensland 4072,
Recently McBride and others have reported the use of Al–F
complexes based upon functionalised bis-carboxylate deriva-
tives of 1,4,7-triazacyclononane for F-18 imaging (Scheme 1).
Incorporation of F-18 via formation of M–F bonds with biolog-
ically relevant ligand scaffolds provides an exciting alternative
to C–F based PET agents.9 McBride et al. have also used the
formation of Al–F bonds to label a wide range of biomolecules
rapidly in a single step.9 However, the need for elevated
temperatures (100 ꢀC) for uorination in this ‘one-pot’
Australia
cSchool of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK. E-mail:
G.Reid@soton.ac.uk; Tel: +44 (0)23 80593609
† Electronic supplementary information (ESI) available: Preparative and
spectroscopic details for the corresponding bromo complexes, HPLC traces and
crystal structures of [GaCl3(Me3-tacn)], [InBr3(Me3-tacn)], [InCl3(BzMe2-tacn)],
[{(Me3-tacn)Ga}2(m-OH)3]Br3$3CH2Cl2 and [NMe4]3[Al2F9] and cif les for all of
the crystal structures. CCDC 926503–926512. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c3sc52104d
This journal is © The Royal Society of Chemistry 2014
Chem. Sci., 2014, 5, 381–391 | 381

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very appealing prospect that rapid, late stage F-18 radiolabelling
of well-dened, pre-formed metal complexes is possible, and
that altering the metal ion to Ga in place of Al may provide
further advantages since it facilitates labelling under mild
conditions. The pH measured for a freshly prepared solution of
[GaCl3(BzMe2-tacn)] in aqueous MeCN was 5.6, while the pH of
reaction formulation comprising [GaCl3(BzMe2-tacn)] and KF in
aqueous MeCN (unbuffered) was 5.9.
Experimental
Scheme 1
Infrared spectra were recorded as Nujol mulls between CsI
plates using a Perkin-Elmer Spectrum100 spectrometer over the
range 4000–200 cmꢁ1. 1H NMR spectra were recorded in CDCl3
or CD2Cl2 unless otherwise stated, using a Bruker AV300 spec-
trometer. 19F{1H} NMR spectra used either a Bruker AV300 or
Bruker DPX400 (376.5 MHz) spectrometer and are referenced
(externally) to CFCl3. 27Al, 71Ga, and 115In NMR spectra were
recorded using a Bruker DPX400 spectrometer and are refer-
enced to aqueous [Al(H2O)6]3+ (104.3 MHz), aqueous
[Ga(H2O)6]3+ (122.0 MHz) and aqueous [In(H2O)6]3+ at pH ¼ 1
(87.7 MHz) respectively. Microanalyses were undertaken by
Medac Ltd. Solvents were dried by distillation prior to use,
CH2Cl2 from CaH2, hexane from sodium benzophenone ketyl
and MeCN from CaH2. MF3$xH2O, MCl3, MBr3 and [nBu4N]F
(1.0 mol dmꢁ3 in thf) (Aldrich) were used as received. Ligands
Me3-tacn18 and BzMe2-tacn19 were prepared via the literature
methods. [Me4N]F (Aldrich) was dried by azeotropic distillation
from toluene. All preparations of chloro and bromo complexes
(ESI†) were performed under an atmosphere of dry N2 using
Schlenk techniques, and spectroscopic samples were prepared
in a dry N2-purged glove box.
approach places some limitations on its utility due to the
thermal instability of some important high MW biomolecules.
In order to further extend the scope of this approach, an
increased understanding of the chemistry and properties of
uoride complexes of the Group 13 elements is required.
Metal uoride coordination complexes are oen signi-
cantly different from those containing heavier halogens.10 The
small, hard and highly electronegative Fꢁ signicantly inu-
ences the electronic environment at the metal centre and hence
the binding of other ligands. For example, while ZrX4 (X ¼ Cl,
Br, I) readily form complexes with so ligands such as phos-
phines and thioethers,11,12 no analogous complexes with ZrF4
are known.13 Further, while GeF4 and WF6 form phosphine
adducts, GeX4 and WCl6 (and WBr6) are reduced to lower
oxidation states. Few studies have been reported on the coor-
dination chemistry of the Group 13 uorides.10,16,17
14
15
We describe here the chemistry of the Group 13 trihalide
complexes [MX3(L)] (L ¼ Me3-tacn, BzMe2-tacn; M ¼ Al, Ga, In;
X ¼ F, Cl, Br) (Scheme 2), and demonstrate that using simple
neutral triaza macrocyclic frameworks, exchange of Clꢁ for Fꢁ
via treatment of the chloro complexes with stoichiometric [R4N]
F (R ¼ nBu or Me) in MeCN solution or with aqueous KF in
MeCN is rapid and complete under mild conditions (weakly
acidic pH) and at room temperature. Further, we demonstrate
that treatment of an aqueous MeCN solution of [GaCl3(BzMe2-
tacn)] with 2.99 mol equiv. of aqueous [19F]–KF and 0.4 mL of
[18F]–KFaq (100–500 MBq) leads to ca. 30% incorporation of the
F-18, forming labelled [GaF3(BzMe2-tacn)] at room temperature
within 30–60 min.
The ease of uoride (both F-18 and F-19) incorporation into
these preformed complexes at room temperature and in mildly
acidic aqueous solution offers potentially signicant advan-
tages over McBride’s ‘Al–F’ system9 which requires elevated
temperature (100 ꢀC) to achieve uoride uptake, since some
biomolecules are unstable at elevated temperatures or under
acidic conditions. Hence, the work reported herein provides the
Preparations
[AlCl3(Me3-tacn)]. AlCl3 (0.067 g, 0.50 mmol) was added to a
solution of Me3-tacn (0.086 g, 0.50 mmol) in CH3CN (5 mL) at
room temperature with stirring which leads to the rapid
formation of a precipitate. Aer 30 min the solvent was removed
by ltration. The white precipitate was washed with a small
amount of CH2Cl2 solvent and dried in vacuo. Yield: 0.11 g, 72%.
Colourless crystals were obtained by cooling the CH3CN solu-
tion in the fridge for several days. Crystals were washed with
CH2Cl2. Required for C9H21AlCl3N3$0.2CH2Cl2: C, 34.4; H, 6.7;
N, 13.1. Found: C, 34.2; H, 7.2; N, 13.9. 1H NMR (CD2Cl2, 298 K):
d 3.23 (m, [6H], tacn-CH2), 2.86 (s, [9H], CH3), 2.67 (m, [6H],
tacn-CH2). IR (Nujol, n/cmꢁ1): 389, 375 (Al–Cl).
[AlF3(Me3-tacn)]$xH2O
Method 1. AlF3$3H2O (0.100 g, 0.73 mmol) was suspended in
freshly distilled water (7 mL). Me3-tacn (0.125 g, 0.73 mmol) was
then added and the pale yellow suspension was transferred into
a Teon container and loaded into a stainless steel high pres-
sure vessel (Parr) and heated to 180 ꢀC for 15 h. The vessel was
then allowed to cool. A dark yellow-brown solution had formed.
A small aliquot of the reaction solution was retained to grow
crystals. For the remaining reaction mixture the volatiles were
removed in vacuo, giving a light brown solid which was washed
Scheme 2
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with hexane and ltered. The resulting white solid was dried in with [NMe4]F (0.042 g, 0.45 mmol) and stirred at room
vacuo. Yield: 0.12 g, 53%. Required for C9H21AlF3N3$3H2O: C, temperature for 1 h. The [NMe4]Cl by-product was removed by
34.9; H, 8.8; N, 13.6. Found: C, 34.3; H, 8.9; N, 14.7%. 1H NMR ltration. The resulting colourless ltrate was treated with 5 mL
(CD3CN, 298 K): d 2.84–2.76 (m, [6H], tacn-CH2), 2.72–2.65 (m, hexane, resulting in a white precipitate which was isolated by
[6H], tacn-CH2), 2.55 (s, [9H], CH3), 2.19 (s, H2O). IR (Nujol, n/ ltration and dried in vacuo. Yield: 0.037 g, 74%. Spectroscopic
cmꢁ1): 3438 br (H2O), 1668 (H2O), 633, 614 (Al–F). Slow evapo- data as for Method 1.
ration of the reaction solvent gave crystals suitable for X-ray
Method 3. [GaCl3(Me3-tacn)] (0.05 g, 0.15 mmol) was suspended
diffraction.
in anhydrous MeCN (5 mL). A solution of KF (0.026 g, 0.45 mmol)
Method 2. A solution of KF (0.058 g, 0.99 mmol) in water in water (2 mL) was added drop-wise, leading to rapid dissolution
(2 mL) was added to a suspension of [AlCl3(Me3-tacn)] (0.100 g, and the formation of a colourless solution. The mixture was
0.33 mmol) in MeCN (5 mL) at room temperature. A white stirred for a further 1 h at room temperature. Quantitative by
precipitate formed initially which redissolved aer a few NMR spectroscopic analysis; data as for Method 1.
minutes. NMR spectroscopic data on the solution were as for
Method 1.
Method 4. GaF3$3H2O (0.150 g, 0.83 mmol) was suspended in
freshly distilled water (7 mL). Me3-tacn (0.142 g, 0.83 mmol) was
[AlCl3(BzMe2-tacn)]. Method as for [AlCl3(Me3-tacn)] but then added and the pale yellow suspension was transferred into
using AlCl3 (0.067 g, 0.50 mmol) and BzMe2-tacn (0.13 g, a Teon container and loaded into a stainless steel high pres-
0.50 mmol). White solid. Yield: 0.13 g, 66%. Required for sure vessel (Parr) and heated to 180 ꢀC for 15 h. The vessel was
C
15H25A1Cl3N3: C, 47.3; H, 6.6; N, 11.0. Found: C, 47.0; H, 6.6; N, then allowed to cool. A yellow-brown solution formed. A small
1
11.2. H NMR (CD2Cl2, 298 K): d 7.31 (m, [5H], ArH), 4.58 (s, aliquot of the reaction solution was retained to grow crystals.
[2H], Ar-CH2), 3.54 (m, [2H], tacn-CH2), 3.29 (m, [4H], tacn-CH2), For the remaining reaction mixture the volatiles were removed
2.92 (s, [6H], CH3), 2.65 (m, [4H], tacn-CH2), 2.28 (m, [2H], tacn- in vacuo, giving a light brown solid which was washed with
CH2). IR (Nujol, n/cmꢁ1): 398, 385 (Al–Cl).
hexane and ltered. The resulting white solid was dried in
1
[AlF3(BzMe2-tacn)]. Method as for [AlF3(Me3-tacn)]$xH2O vacuo. Yield: 0.21 g, 84%. H NMR (CD3CN, 298 K): d 2.84 (m,
above, using [AlCl3(BzMe2-tacn)] and aqueous KF. 1H NMR [6H], tacn-CH2), 2.72 (m, [6H], tacn-CH2), 2.63 (s, [9H], CH3). IR
(CD3CN, 298 K): d 7.62 (m, [5H], ArH), 4.26 (s, [2H], Ar-CH2), 3.01 (Nujol, n/cmꢁ1): 529, 492 (Ga–F).
(m, [4H], tacn-CH2), 2.89 (m, [4H], tacn-CH2), 2.85 (s, [6H], CH3),
[GaCl3(BzMe2-tacn)]. Method as for [GaCl3(Me3-tacn)] but
2.74 (m, [4H], tacn-CH2), 1.53 (br s, H2O). IR (Nujol, n/cmꢁ1): 3392 using BzMe2-tacn (0.125 g, 0.50 mmol) and GaCl3 (0.088 g, 0.50
br (OH), 1665 (H2O), 1639 (Bz aromatic CC), 635, 601 (Al–F).
[GaCl3(Me3-tacn)]. Me3-tacn (0.09 g, 0.52 mmol) was added
mmol). White solid. Yield: 0.089 g, 42%. Required for
15H25Cl3GaN3: C, 42.5; H, 6.0; N, 9.9. Found C, 42.2; H, 6.0; N,
C
1
to a solution of GaCl3 (0.088 g, 0.50 mmol) in anhydrous CH2Cl2 9.6%. H NMR (CD2Cl2, 298 K): d 7.30 (br m, [5H], ArH), 4.71
(8 mL) at room temperature with stirring. Aer ca. 30 min, a (s, [2H], Ar-CH2), 3.67 (br, [2H], tacn-CH2), 3.20 (br, [2H], tacn-
white precipitate started to appear. Aer 2 h stirring was CH2), 2.92 (br s, [6H], CH3), 2.75 (br m, [2H], tacn-CH2), 2.62 (br
stopped and the mixture was concentrated to afford more m, [2H], tacn-CH2), 2.40 (br m, [2H], tacn-CH2). IR (Nujol, n/
precipitate, the white powdered product was ltered from the cmꢁ1): 301, 280 (Ga–Cl).
solution and dried in vacuo. Yield: 0.110 g, 60%. Required for
[GaF3(BzMe2-tacn)]$xH2O
C9H21Cl3GaN3: C, 31.1; H, 6.1; N, 12.1. Found C, 31.2; H, 5.9; N,
Method 1. [GaCl3(BzMe2-tacn)] (0.05 g, 0.10 mmol) was sus-
1
12.1%. H NMR (CD2Cl2, 298 K): d 3.2 (br m, [6H], tacn-CH2), pended in 5 mL anhydrous CH2Cl2. The suspension was treated
2.85 (br s, [9H], Me), 2.6 (br m, [6H], tacn-CH2). IR (Nujol, n/ with [NMe4]F (0.03 g, 0.30 mmol) and stirred at room tempera-
cmꢁ1): 290, 275 (Ga–Cl).
[GaF3(Me3-tacn)]$xH2O
ture for 1 h. The [NMe4]Cl by-product was removed by ltration.
The resulting colourless ltrate was treated with 5 mL anhydrous
Method 1. [GaCl3(Me3-tacn)] (0.1 g, 0.28 mmol) was added to hexane, forming a white precipitate which was isolated by
CH2Cl2 (8 mL) and stirred for ca. 15 min, the solid mostly dis- ltration and dried in vacuo. Yield: 0.035 g, 80%. Required for
solved to give a clear solution. [NnBu4]F in thf (1 mol dmꢁ3, 0.84 C15H25F3GaN3$4H2O: C, 40.4; H, 8.8; N, 8.6. Found C, 40.9; H, 8.8;
mL, 0.84 mmol) was added to the mixture via syringe and the N, 8.6%. 1H NMR (D2O, 298 K): d 7.30 (m, [5H], ArH), 4.73 (s, [2H],
reaction was stirred for ca. 10 min, giving a clear, colourless Ar-CH2), 3.17 (m, [4H], tacn-CH2), 2.88 (m, [4H], tacn-CH2), 2.73
solution. The solution was ltered and the ltrate was taken to (s, [6H], CH3), 2.36 (m, [4H], tacn-CH2), 2.25 (s, H2O). IR (Nujol, n/
dryness in vacuo. The resulting colourless solid was re-dissolved cmꢁ1): 3390, 1654 (H2O), 526, 515 (Ga–F).
in CH2Cl2, the solution was ltered and the CH2Cl2 was le to
Method 2. As described for [GaF3(Me3-tacn)] Method 3, using
evaporate, giving a colourless solid product. Yield: 50%. Required [GaCl3(BzMe2-tacn)] (0.05 g, 0.10 mmol) and KF (0.017 g, 0.30
for C9H21F3GaN3$3H2O: C, 30.7; H, 7.7; N, 11.9. Found: C, 30.6; mmol) in water. White solid. 0.035 g, 73%. Spectroscopic data
H, 6.9; N, 11.0%. 1H NMR (CD2Cl2, 298 K): d 2.85–2.94 (br m, [6H], as for Method 1.
tacn-CH2), 2.67 (s, [9H], Me), 2.55–2.61 (br m, [6H], tacn-CH2, 2.17
[InCl3(Me3-tacn)]. Method as for [GaCl3(Me3-tacn)], but using
(s, H2O)). IR (Nujol, n/cmꢁ1): 3481, 3429 (H2O), 1648 (H2O), 530, Me3-tacn (0.086 g, 0.50 mmol) and InCl3 (0.110 g, 0.50 mmol).
492 (Ga–F). Colourless crystals were grown from the CH2Cl2 White solid. Yield: 0.113 g, 57%. Required for C9H21Cl3InN3: C,
1
solution of the product upon slow evaporation.
27.5; H, 5.4; N, 10.7. Found C, 27.8; H, 5.4; N, 10.9%. H NMR
Method 2. [GaCl3(Me3-tacn)] (0.05 g, 0.15 mmol) was sus- (CDCl3, 298 K): d 3.1 (br m, [6H], tacn-CH2), 2.8 (br m, [15H], Me
pended in 5 mL anhydrous CH2Cl2. The suspension was treated and tacn-CH2). IR (Nujol, n/cmꢁ1): 287, 269 (In–Cl).
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[InF3(Me3-tacn)]$xH2O
F-18 radiolabelling of [GaCl3(BzMe2-tacn)]
Method 1. [InCl3(Me3-tacn)] (0.214 g, 0.54 mmol) was added to
CH2Cl2 (8 mL) and stirred for ca. 15 min, this gave a cloudy
suspension. [NnBu4]F in thf (1 mol dmꢁ3, 1.63 mL, 1.63 mmol)
was added to the mixture via a syringe and stirred for ca. 2 h.
The solution was ltered and the white precipitate collected,
washed with hexane and dried in vacuo. Yield: 0.150 g, 70%.
Required for C9H21F3InN3$H2O: C, 29.9; H, 6.4; N, 11.6. Found:
Experiments were analysed on a Gilson 322 HPLC system with a
Gilson 156 UV detector. Dionex Chromeleon 6.8 Chromatog-
raphy data recording soware was used to integrate the UV and
radiochemical peak areas. Preparative HPLC: Luna 5m C18(2)
100 ꢂ 10 mm (mobile phase A ¼ 100% water; B ¼ 100% MeCN).
Flow rate 3 mL minꢁ1. Gradient 0 to 5 min (10% B), 5–20 min
(10–90% B), 20–25 min (90% B), 25–26 min (10% B).
Analytical HPLC: Luna 5m C18(2) 250 ꢂ 4.6 mm (mobile
phase A ¼ 10 mM ammonium acetate, B ¼ 100% MeCN). Flow
rate 1 mL minꢁ1. Gradient 0–15 min (10–90% B), 15–20 min
(90% B), 20–21 min (90–10% B), 21–26.5 min (10% B).
ESI+ mass spectra were recorded from direct injection of the
products onto a Thermo Finnigan mass spectrometer tted with
an LCQ advantage MS pump.
Procedure: In a typical experiment [GaCl3(BzMe2-tacn)] (0.001
g, 2.36 mmol) was dissolved in a mixture of MeCN (0.5 mL) and
H2O (0.1 mL). This solution was added to 0.4 mL of an aqueous
solution containing [18F]–KF (100 to 500 MBq) and [19F]–KF
(7.05 mmol) and the vial was allowed to stand at room temper-
ature for 30 to 60 min. The crude reaction solution was diluted
with water so that approximately 10% of the solvent composi-
tion was organic. Preparative HPLC on the diluted crude reac-
tion solution conrmed ca. 30% incorporation of F-18 into the
metal complex (based upon integration of the radio peaks) aer
one hour. Peak 1: Rt ¼ 2.2 min (18Fꢁ). Peak 2: Rt ¼ 9.0 min
(complex). The MeCN was then removed in vacuo and the
product was made up with PBS and ethanol to give a ca. 10%
ethanol nal product (pH 7.2).
1
C, 29.9; H, 6.1; N, 11.5%. H NMR (CD2Cl2, 298 K): d 3.09–3.15
(br m, [6H], tacn-CH2), 2.93 (m, [9H], Me), 2.72–2.82 (br m, [6H],
tacn-CH2), 2.19 (s, H2O). IR (Nujol, n/cmꢁ1): 3392 br (H2O), 1669
(H2O), 479, 462, 443 (In–F). Colourless crystals were grown from
the CH2Cl2 solution of the product upon slow evaporation.
Method 2. [InCl3(Me3-tacn)] (0.060 g, 0.17 mmol) was sus-
pended in 5 mL anhydrous CH2Cl2. The suspension was treated
with [NMe4]F (0.047 g, 0.51 mmol) and stirred at room
temperature for 1 h. The [NMe4]Cl by-product was removed by
ltration. The resulting colourless ltrate was treated with 5 mL
anhydrous hexane, forming a white precipitate which was iso-
lated by ltration and dried in vacuo. Yield: 0.044 g, 76%.
Spectroscopic data as for Method 1.
Method 3. A Teon reactor vessel was charged with freshly
distilled water (7 mL), InF3$3H2O (0.200 g, 0.90 mmol) and Me3-
tacn (0.154 g, 0.90 mmol). The Teon container was loaded into
a stainless steel high pressure vessel (Parr) and heated to 180 ꢀC
for 15 h. The vessel was then allowed to cool. A dark yellow-
brown solution had formed. A small aliquot of the reaction
solution was retained to grow crystals. For the remaining reac-
tion mixture the volatiles were removed in vacuo, giving a light
brown gum which was washed with hexane. The hexane was
decanted and the remaining volatiles removed in vacuo to give a
light brown solid. Yield 0.246 g, 0.62 mmol, 69%. Spectroscopic
data as for Method 1.
Peak 2 was run through an analytical HPLC system giving a
single radio and UV peak at Rt 6.2 min (RCP 99%).
Peak 2: ESI+ MS (MeCN/NH4OAc): found m/z
¼
354
[GaF2(BzMe2-tacn)]+; 391 [GaF3(BzMe2-tacn)
+
NH4]+. The
[InCl3(BzMe2-tacn)]. Method as for [GaCl3(Me3-tacn)], but
using BzMe2-tacn (0.125 g, 0.50 mmol) and InCl3 (0.110 g, 0.50
mmol). White solid. Yield: 0.093 g, 40%. Required for
product is stable to chemical and radiochemical degradation
for at least two hours in phosphate buffered saline and ethanol
– see ESI.†
C
15H25Cl3InN3: C, 38.5; H, 5.4; N, 9.0. Found C, 38.8; H, 5.8; N,
1
8.7%. H NMR (CD3CN, 298 K): 7.2–7.4 (m, [5H], ArH), 4.37 (s,
[2H], Ar-CH2), 3.45 (br, [2H], tacn-CH2), 3.10 (br, [2H], tacn-
CH2), 2.80 (s, [6H], CH3), 2.75 (br m, [2H], tacn-CH2), 2.60 (br m,
[2H], tacn-CH2), 2.40 (br m, [2H], CH2). IR (Nujol, n/cmꢁ1): 289,
271 (In–Cl). Crystals formed from the CH2Cl2 solution of the
X-ray crystallography
Details of the crystallographic data collection and renement
parameters are given in the ESI.† Crystals were obtained as
described. Data collection used a Rigaku AFC12 goniometer
equipped with an enhanced sensitivity (HG) Saturn724+ detector
mounted at the window of an FR-E+ SuperBright molybdenum
rotating anode generator with VHF Varimax optics (100 mm
focus) with the crystal held at 120 K (N2 cryostream) or a Bruker-
Nonius FR591 rotating anode diffractometer tted with confocal
mirrors and with the crystal held at 120 K (N2 cryostream). Mo-Ka
ꢀ
product stored in the freezer at ꢁ18 C.
[InF3(BzMe2-tacn)]$xH2O. [InCl3(BzMe2-tacn)] (0.06 g, 0.10
mmol) was suspended in 5 mL anhydrous CH2Cl2. The
suspension was treated with [NMe4]F (0.03 g, 0.30 mmol) and
stirred at room temperature for 1 h. The [NMe4]Cl by-product
was removed by ltration. The resulting colourless ltrate was
treated with 5 mL anhydrous hexane, forming in a white
precipitate which was isolated by ltration, washed with hexane
and dried in vacuo. Yield: 0.02 g, 48%. C15H25F3InN3$3H2O: C,
38.1; H, 6.6; N, 8.9. Found C, 37.6; H, 5.2; N, 8.6%. 1H NMR
(CD3CN, 298 K): 7.37 (m, [5H], ArH), 4.37 (s, [2H], Ar-CH2), 3.08
(m, [6H], CH3), 2.91 (m, [4H], tacn-CH2), 2.80 (m, [4H], tacn-
CH2), 2.64 (m, [4H], tacn-CH2). IR (Nujol, n/cmꢁ1): 3450 v br
(H2O), 1651 (H2O), 481, 463 (In–F).
˚
X-radiation (l ¼ 0.71073 A). Structure solution and renement
were generally routine,20,21 except as described below, with
hydrogen atoms on C added to the model in calculated positions
and using the default C–H distance. For [AlCl3(Me3-tacn)] the
data were collected as orthorhombic, but during the structure
solution it became clear that in fact the crystal was monoclinic.
The data were therefore reprocessed as monoclinic, giving 96%
completeness. The renement used TWIN/BASF commands to
model disorder. For [InCl3(BzMe2-tacn)] the crystal quality was
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rather poor, hence the nal residuals are higher than normal, involved in an array of H-bonding interactions both with the F
although the coordination environment is not in doubt.
atoms in the [AlF3(Me3-tacn)], as well as between the H2O
molecules themselves, giving H2O/F1 ¼ 2.806(3), H2O/F2 ¼
˚
2.701(3), H2O/F3 ¼ 2.688(3), H2O/F1 ¼ 2.802(4) A. This gives
rise to the extensively H-bonded array illustrated in Fig. 1(b).
Results and discussion
The GaF3 analogue, [GaF3(Me3-tacn)]$4H2O, obtained and
The Group 13 uorides, MF3$3H2O, are poorly soluble in organic characterised similarly, also crystallises as a tetrahydrate
solvents, and hence there are rather few examples where these have (below). These [MF3(Me3-tacn)]$4H2O species are remarkably
been used directly to form metal uoro-complexes with neutral stable in the solid and also in solution in H2O, CH2Cl2, MeCN
ligands under conventional conditions.10 Notable exceptions
include mer-[GaF3(pyridine)3] (prepared by prolonged reuxing of
etc. This led us to consider the possibility of that introduction of
Fꢁ via exchange reactions with the heavier halide analogues
the constituents in thf),22 [GaF3{1,4,7-tris(2-amino-3,5-di-butylben- (Clꢁ or Brꢁ) may be synthetically viable and serve as an alter-
zyl)-1,4,7-triazacyclononane}],23 and direct reaction of InF3$3H2O native route to the [MF3(Me3-tacn)] (M ¼ Al, Ga or In), by virtue
with 2,20-bipy or 1,10-phen (L–L) forms the distorted octahedral of the M–F bonds formed being stronger than those involving
species [InF3(L–L)(H2O)].24 Diimine and amine complexes of MF3 the heavier halides.10
(M ¼ Al, Ga, In) have been obtained using hydrothermal syntheses
In order to test this idea, the complexes, fac-[MX3(Me3-tacn)]
at elevated temperature (ꢃ180 C),25 while reaction of AlN or InN (M ¼ Al, Ga, In; X ¼ Cl, Br) and [MX3(BzMe2-tacn)] (M ¼ Al, X ¼
ꢀ
and NH4F in supercritical ammonia (400 ꢀC) forms [AlF3(NH3)2]
and [InF2(NH2)(NH3)] respectively.26
Cl, Br; M ¼ Ga, X ¼ Cl; M ¼ In; X ¼ Cl or Br) were obtained in
high yield from direct reaction of MX3 with the triaza macrocycle
Direct reaction of AlF3$3H2O and Me3-tacn under hydro- in anhydrous CH2Cl2 or MeCN. Conrmation of their identities
thermal conditions (180 ꢀC, 15 h) led to formation of [AlF3(Me3- follows from microanalyses, IR and 1H NMR spectroscopic data
tacn)]$4H2O as a white solid in good yield. The IR spectrum and from crystal structures of representative examples.
shows two bands in the far-IR region attributed to the a1 and e
Multinuclear solution 27Al, 71Ga and 115In NMR studies
stretching modes from the facial MF3 unit of a distorted octa- support the formulations – Table 1. For the Al and Ga
hedron (C3v). There is also clear evidence for H-bonded H2O, complexes, the spectra show a single resonance despite the
moderate quadrupole moments associated with the 27Al and
which turn out to be an important feature of these complexes
71Ga [I ¼ 3/2, 39.6% abundance, Q ¼ 0.112 ꢂ 10ꢁ28 m2, RC
¼
1
and is described in more detail below. The H NMR spectrum
(CD3CN) is characteristic of facially coordinated Me3-tacn. NMR 322] nuclei. This is consistent with the proposed distorted six-
spectroscopic measurements in D2O also conrm the stability coordinate geometry with local C3v symmetry, leading to the
of the triuoro species in aqueous solution. The 27Al [I ¼ 5/2, electric eld gradient (EFG) being close to zero, and hence
100% abundance, Q ¼ 0.149 ꢂ 10ꢁ28 m2, RC ¼ 1170] and 19F{1H} relatively sharp lines.27 The 115In NMR spectra were less infor-
NMR spectra (Table 1) each show a singlet.
mative due to the much larger quadrupole moment, which
The crystal structure is consistent with the spectroscopic sometimes led to the resonance not being observed for [InX3(R3-
tacn)] (X ¼ Cl or Br) [115In: I ¼ 9/2, 95.7% abundance, Q ¼ 1.16
data, conrming the distorted octahedral coordination at Al via
ꢂ 10ꢁ28 m2, RC ¼ 1920]. The multinuclear NMR studies show
a tridentate Me3-tacn ligand and three fac Fꢁ ligands (Fig. 1(a)).
The asymmetric unit contains four H2O molecules as well that the chloro complexes are more resistant to hydrolysis/
as one [AlF3(Me3-tacn)] molecule. The water molecules are solvolysis in solution than the bromo species, and that while the
Table 1 Multinuclear NMR spectroscopic data
Complex
d
27Al/71Ga/115In/ppm; (w1/2/Hz)
d
19F{1H} (ppm)
Solvent
[AlF3(Me3-tacn)]
19.0 (60); 18.5 (52)
34.5 (30)
ꢁ176.1; ꢁ169.9
MeCN; D2O
CH2Cl2
CH2Cl2
CH2Cl2; D2O
CH2Cl2
MeCN
MeCN; D2O
CH2Cl2
MeCN
[AlCl3(Me3-tacn)]
[AlBr3(Me3-tacn)]
[GaF3(Me3-tacn)]
[GaCl3(Me3-tacn)]
[GaBr3(Me3-tacn)]
[InF3(Me3-tacn)]
[InCl3(Me3-tacn)]
[InBr3(Me3-tacn)]
[AlF3(BzMe2-tacn)]
[AlCl3(BzMe2-tacn)]
[AlBr3(BzMe2-tacn)]
[GaF3(BzMe2-tacn)]
[GaCl3(BzMe2-tacn)]
[InF3(BzMe2-tacn)]
[InCl3(BzMe2-tacn)]
—
18.9 (80)
—
42.0 (q, 1JGaF ꢃ 490 Hz); 44.6 (br q)
ꢁ180.9 (two br q); ꢁ173 (br)
93.9 (60)
—
—
ꢁ29.3 (180)
64 (q, 1JInF ꢃ 600 Hz); n.o.
268 (750)
ꢁ215 (br); ꢁ192.5 (br)
—
—
n.o.a
19.8 (100)
ꢁ161.5 (F), ꢁ161.7 (2F)
MeCN
36.5 (45)
20.1 (35)
—
—
CH2Cl2
CH2Cl2
D2O
MeCN
MeCN
44.9 (q 1JGaF ꢃ 445Hz)
92.8 (360)
ꢁ172.8 (br)
—
n.o.a
ꢁ220 (br)
265 (2200)
—
MeCN
a
n.o. ¼ not observed.
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Fig. 1 (a) Structure of [AlF3(Me3-tacn)]$4H2O showing the atom labelling scheme. Ellipsoids are drawn at the 40% probability level and H atoms
bonded to C are omitted for clarity. (b) View along the a-axis of the extended structure assembled through intermolecular H-bonding (colour
key: teal ¼ Al, green ¼ F, blue ¼ N, red ¼ O, black ¼ C).
complexes are stable in anhydrous CH2Cl2 or MeCN, stronger and Me3SiF in pyridine affords [AlF2(py)4]Cl.29 However, for F-18
donor solvents such as dmf or dmso lead to decomposition. The applications, the radio-uorine is produced as Fꢁ ions, and hence
powdered solids may be stored under N2 for many months it is more desirable to be able to use the uoride directly as Na18F
without degradation.
(or K18F or R4N18F). Therefore, in this work we have investigated
Trace hydrolysis of [GaX3(Me3-tacn)] (X ¼ Cl or Br) produces both tetraalkylammonium uorides (in organic solvents) and
the face-sharing bioctahedral dimers [{(Me3-tacn)Ga}2(m-OH)3] aqueous KF as the uoride source.
X3$3CH2Cl2, and the crystal structure of the Br derivative was
Initial studies were performed by addition of three mol equiv.
also determined (ESI†). Wieghardt and co-workers have of a 1 mol dmꢁ3 thf solution of [NnBu4]F to a suspension of
described the hydrolysis of [InCl3(Me3-tacn)] to form dinuclear [MCl3(R3-tacn)] in MeCN. For the Ga systems this led to rapid and
m-hydroxy and tetranuclear m-oxo derivatives.28
complete dissolution at room temperature over ca. 5 min, and in
While the bromo complexes are readily hydrolysed, the situ 71Ga and 19F{1H} NMR studies (Table 2) show complete
chloro species are much more stable, and therefore considered conversion to [GaF3(R3-tacn)]. For the more symmetrical Me3-tacn
excellent candidates for the uorination studies.
system, a quartet is observed in the 71Ga NMR spectrum (MeCN)
due to coupling to three Fꢁ ligands (d71Ga ¼ 42.0, 1JGaF ꢃ 490 Hz –
Fig. 2), and although not fully resolved, the 19F{1H} NMR spectrum
Clꢁ/19Fꢁ exchange reactions
Reagents such as Me3SiF and Me3SnF are oen convenient uo- shows a single resonance (ꢁ180.0 ppm) with coupling to 69/71Ga,
ride sources in synthetic chemistry, e.g. [AlCl3(py)n] (n ¼ 1 to 3) providing unequivocal evidence for formation of [GaF3(Me3-tacn)].
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Table 2 Key structural data for [MX3(L)]
:(X–M–X)/ꢀ
:(N–M–N)/ꢀ
˚
˚
Complex
d(M–X)/A
d(M–N)/A
[AlF3(Me3-tacn)]$4H2O
[AlCl3(Me3-tacn)]
1.740(2), 1.744(2), 1.757(2) 2.098(3), 2.106(3), 2.115(3)
2.267(2), 2.274(2), 2.276(2) 2.111(3), 2.126(4), 2.141(4)
1.851(3), 1.858(3), 1.881(3) 2.126(4), 2.126(4), 2.140(4)
96.65(12), 96.00(11), 95.81(12) 82.20(13), 82.13(13),
82.37(13)
94.03(7), 93.74(6), 94.21(7)
83.03(14), 81.64(14),
81.97(14)
[GaF3(Me3-tacn)]$4H2O
95.81(12), 94.87(13), 94.23(12) 82.2(1), 82.4(2), 81.6(2)
[GaCl3(Me3-tacn)]
2.3087(5), 2.3177(9),
2.3217(5)
2.0318(11), 2.0391(12),
2.0570(11)
2.5987(8), 2.6006(8),
2.6046(8)
2.1644(13), 2.1755(13),
2.1960(14)
2.287(2), 2.289(2), 2.291(2)
94.38(2), 93.98(2), 94.49(2)
96.33(5), 95.04(5), 94.79(5)
96.66(3), 95.06(2), 96.15(3)
96.72(5), 96.72(5), 98.24(5)
95.32(5), 96.26(5), 98.31(5)
81.90(5), 80.80(5),
80.83(5)
78.68(6), 78.91(6),
78.44(6)
[InF3(Me3-tacn)]$4H2O
[InBr3(Me3-tacn)]$CH2Cl2
2.344(4), 2.345(5), 2.347(4)
2.312(4), 2.342(4), 2.371(4)
2.312(4), 2.342(4), 2.371(4)
76.4(2), 76.8(2), 76.2(2)
[InF3(BzMe2-tacn)]$1.2H2O 2.4443(13), 2.4518(14),
77.96(6), 77.14(6),
77.80(6)
77.1(2), 77.4(2), 76.3(2)
2.4581(14)
2.4443(13), 2.4518(14),
2.4581(14)
[InCl3(BzMe2-tacn)]
the Ga systems. The 115In spectrum (MeCN) of [InF3(Me3-tacn)]
shows a well-resolved 1 : 3 : 3 : 1 quartet (Fig. 4) at 64 ppm (1JInF
ꢃ 600 Hz), conrming the complete exchange of Clꢁ for Fꢁ.
Both [InF3(Me3-tacn)]$4H2O (Fig. 5) and [InF3(BzMe2-tacn)]$
1.2H2O (Fig. 6) were also characterised crystallographically.
Although none of the [MF3(Me3-tacn)] complexes in this study are
isomorphous, they all adopt very similar structures and crystal-
lise as tetrahydrates, showing a very strong tendency for the F
ligands to engage in extensive F/H–OH hydrogen-bonding,
while [InF3(BzMe2-tacn)]$1.2H2O, shows the H2O molecules form
˚
signicant interactions with F1 and F2, F/H–OH ꢃ 2.8 A.
Unlike the Ga and In analogues, [AlCl3(Me3-tacn)] does not
react with either [NnBu4]F or [NMe4]F in neat MeCN at room
temperature, even over several hours. Heating the reaction
mixture causes partial decomposition, forming [AlF4]ꢁ and
releasing the R3-tacn, but there is no evidence in the 19F{1H} and
27Al NMR spectra for formation of [AlF3(Me3-tacn)] under these
conditions. This was unexpected, and the reason for the failure
is not entirely clear, however, it may be a result of the smaller
ionic radius of Al3+, which would disfavour an associative (A) or
associative interchange (Ia) ligand substitution mechanism.
However, we were able to demonstrate that addition of aqueous
KF to a MeCN suspension of [AlCl3(Me3-tacn)] does lead to clean
conversion to form [AlF3(Me3-tacn)] at room temperature, the
spectroscopic signature of the product matching that formed
via hydrothermal synthesis from AlF3$3H2O (above). This
suggests that the more polar (cf. MeCN) H2O solvent is involved
in a solvent assisted substitution mechanism.30
Fig. 2 71Ga NMR spectrum of [GaF3(Me3-tacn)] (CH2Cl2) showing the
quartet coupling (1JGaF ꢃ 490 Hz).
Notably, like [AlF3(Me3-tacn)], [GaF3(Me3-tacn)] also crystal-
lises as a tetrahydrate, [GaF3(Me3-tacn)]$4H2O (Fig. 3), with an
extensive H-bonding array involving intermolecular O/F and
O/O interactions.
The [GaF3(R3-tacn)] complexes were subjected to a range of
experimental conditions that showed the triuoro-complexes
are unaffected by (i) prolonged heating (2 h at 40–50 ꢀC) in
MeCN, (ii) the presence of a 10-fold excess of Clꢁ in MeCN, (iii)
standing for several days in aqueous solution, (iv) the presence
of acid (aqueous HBF4) and (v) the presence of excess Fꢁ either
in MeCN or H2O.
For the gallium systems, clean uorination is also effected
using [NMe4]F in MeCN (the [NMe4]Cl by-product is more
F-18 radiolabelling
readily separated than [NnBu4]Cl). Addition of aqueous KF to a Based upon the results from the Clꢁ/19Fꢁ exchange reactions
suspension of [GaCl3(R3-tacn)] in MeCN also leads to rapid and the gallium(III) systems were identied as the most promising
complete uorination at room temperature. This conrms that candidate for the F-18 radiolabelling experiments. Further-
Clꢁ/Fꢁ exchange is faster than any competing hydrolysis reac- more, inclusion of the benzyl chromophore in [GaCl3(BzMe2-
tions under these conditions.
tacn)] allows the fate of the complex to be monitored in parallel
The [InCl3(R3-tacn)] behave similarly with both [NR4]F in with the radio-trace by using UV-visible spectroscopy. Radio-
MeCN, although the Clꢁ/Fꢁ exchange reaction is slower (ca. 30– labelling was carried out on a 1 mg scale by dissolving
45 min) to reach completion at room temperature compared to [GaCl3(BzMe2-tacn)] in aqueous MeCN, adding 2.99 mol equiv.
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Fig. 3 (a) View of the structure of [GaF3(Me3-tacn)]$4H2O with numbering scheme adopted. Ellipsoids are shown at the 40% probability level and
H atoms (except those on the H2O molecules) are omitted for clarity. (b) View down the c-axis of the extended structure showing the H-bonding
interactions (colour key: turquoise ¼ Ga, green ¼ F, blue ¼ N, red ¼ O, black ¼ C).
of aqueous [19F]–KF and 0.4 mL of [18F]–KFaq (100–500 MBq) one mol equiv. of [NH4][PF6] leads to the appearance of a strong
and allowing the solution to stand at room temperature for peak at m/z ¼ 391.
between 30 and 60 min. The crude reaction solution was puri-
This behaviour is attributed to the presence of the highly
ed by preparative HPLC using a water–MeCN mobile phase. electronegative facial GaF3 fragment which can form electrostatic
This gave a single product peak at Rt ¼ 9.0 min (ca. 30% and/or H-bonding interactions with the hard [NH4]+ cation
incorporation aer one hour). The puried species was eluted introduced during the labelling experiments and HPLC analysis –
through an analytical HPLC system using a 10 mM aq. NH4OAc– similar to the strong F/H–OH interactions to the associated
MeCN mobile phase, giving a single peak in the radio-chro- water molecules observed crystallographically (vide supra). There
matograph at Rt ¼ 6.1 min. ESI+ mass spectrometric analysis of is also literature precedent for this behaviour in alkaline earth or
this species post elution gave an m/z and isotope pattern lanthanide complexes of AsF3 such as [Ca(AsF3)(AsF6)2], in which
consistent with the species [GaF3(BzMe2-tacn) + NH4]+ (m/z ¼ the pyramidal AsF3 molecule behaves as a Lewis base, bonding to
391; 100%) – see ESI.† The presence of associated [NH4]+ in the metal cation via bridging uorides (with further interactions
these species was also conrmed from independent mass between Ca2+ and the [AsF6]ꢁ anions).31
spectrometry experiments on the preformed [GaF3(BzMe2-tacn)]
The puried species was dried under vacuum and treated
complex with and without added cation. Thus, introduction of with phosphate buffered saline (PBS) and ethanol, giving a
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Fig. 6 Structure of [InF3(BzMe2-tacn)]$H2O with atom numbering
scheme. Ellipsoids are shown at the 50% probability level and H atoms
(except those on O1) are omitted for clarity.
specically for [MX3(Me3-tacn)] (M ¼ Al, X ¼ Cl; M ¼ Ga, X ¼ Cl;
M ¼ In, X ¼ Br) – Fig. 7 and ESI, and for [InCl3(BzMe2-tacn)]
(ESI†). Each structure shows the expected distorted octahedral
coordination environment at M, comprising a tridentate tri-
amine macrocycle and three mutually facial X ligands.
Fig. 4 115In NMR spectrum of [InF3(Me3-tacn)] (MeCN). The splitting
pattern arises through the coupling of three equivalent fluorides to the
indium centre (1JInF ꢃ 600 Hz).
In contrast to the uorides, the chloro- and bromo-
complexes are discrete molecular entities, and show no incor-
poration of solvent molecules in the crystal lattice.
Table 2 summarises the key geometric parameters for the series
of complexes. Comparing the M–N and M–F distances within the
series [MF3(Me3-tacn)]$4H2O (M ¼ Al, Ga, In) reveals that upon
˚
going from Al to Ga the M–F bond distances increase by ꢃ0.12 A,
˚
and from Ga to In the increase is ꢃ0.19 A. These changes are
almost exactly in line with expectation based on the increasing
ionic radii for the six-coordinate trivalent metal ions down Group
3+
3+
13 (Al3+ ¼ 0.535 A; Ga ¼ 0.62 A; In ¼ 0.80 A).
32
˚
˚
˚
In contrast however, the M–N bond distances for Ga complex
˚
are only ꢃ0.02 A longer than for the Al complex, whereas from
˚
Ga to In the M–N bonds increase by ꢃ0.17 A. Also, comparing
the Al–N bond distances in [AlF3(Me3-tacn)]$4H2O with those in
˚
[AlCl3(Me3-tacn)] reveals a very small increase of only ꢃ0.02 A,
whereas in the Ga systems [GaF3(Me3-tacn)]$4H2O the Ga–N
Fig. 5 View of the structure of [InF3(Me3-tacn)]$4H2O with numbering
scheme adopted and showing the F/H–O interactions. Ellipsoids are
˚
distances are ca. 0.04–0.05 A shorter than in [GaCl3(Me3-tacn)].
shown at the 40% probability level and H atoms (except those on the These observations suggest that the 9-membered triaza
H2O molecules) are omitted for clarity.
formulation of 10% ethanol with pH 7.2. Subsequent analysis
by analytical HPLC conrmed that the species was stable under
these conditions for at least 2 hours. The radiochemical purity
(RCP) of the puried product remained high over this period
(98ꢁ99% RCP) – ESI.†
X-ray structural comparisons
In view of the very different stabilities of the [MX3(R3-tacn)]
complexes and the differing reactivities towards Fꢁ/Clꢁ
exchange observed across the series, it was of interest to
compare the structural properties of the species to attempt to
ascertain any signicant structural trends which might provide
some insights. For comparison with the triuoro complexes
already described, crystal structures of [MX3(R3-tacn)] were
Fig. 7 Structure of [AlCl3(Me3-tacn)] with atom numbering scheme.
Ellipsoids are shown at the 50% probability level and H atoms are
therefore determined for a range of M with X ¼ Cl or Br, omitted for clarity.
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macrocycle may be too large for optimal facial coordination to
the smallest Al3+ ion, whereas the larger Ga3+ and In3+ t rather
better. This may also account for the differences observed in the
Clꢁ/Fꢁ exchange reactions in MeCN solution; i.e. the Al3+ centre
is sterically less accessible to the Fꢁ entering group in MeCN,
whereas the halide exchange in aqueous MeCN probably
undergoes a solvent (H2O) assisted substitution.
The trend in X–M–X and N–M–N angles across the series
correlates with the trends in bond distances. In all cases the
angles involving halide ligands are ꢃ94–98ꢀ, with no obvious
trend with changing X or M. In contrast, the N–M–N angles in
the Al3+ and Ga3+ complexes are essentially invariant (ꢃ82ꢀ),
while those involving In3+ are rather more acute, ꢃ77ꢀ, reect-
ing the elongated In–N bond distances.
Notes and references
1 G. Bandoli, A. Dolmella, F. Tisato, M. Porchia and F. Refosco,
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Acknowledgements
We thank GE Healthcare and the EPSRC for a CASE studentship
(G. S.). We also thank Dr M. Webster for assistance with the
crystallographic analyses, J. Ali (GE Healthcare) for support on
the mass spectrometry studies and Dr G. J. Langley (South-
ampton) for helpful discussions.
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