Imaging plate and radiation counting
and J \ 3.4 Hz). 13C NMR (CDCl ): d 14.2 (C-16), 28.2 (C-
HvH
3
17), 39.2 (C-18), 47.3 (C9, C-11), 49.2 (C-2 to C-6), 51.3 (C-8,
C-12), 57.0 (C-13), 60.7 (C-15), 123.4 (C-21), 131.7 (C-20), 134.2
(C-22), 167.7 (C-19), 170.3È171.1 (C-14). Anal. calc. for
The imaging plate consisted of a Ñexible plastic coated with
Ðne photostimulable phosphor crystals (BaFBr : Eu ] 2)
capable of storing a fraction of the absorbed incident energy
from irradiation with electrons or photons. When later stimu-
lated by visible or infrared radiation, these crystals emit
photostimulated luminescence at an intensity proportional to
the absorbed radiation energy. The imaging plate system has
several advantages compared to other image sensors: ultra-
high sensitivity, a wider dynamic range, superior linearity and
better spatial resolution.
Gamma counting was carried out using a Beckman model
310 counter with appropriate energy windows set for 57Co.
TLC plates containing radiolabelled materials were visualised
on a phosphor imager 445 SI imaging system (Molecular
Dynamics, USA, model 410A).
C
H
N O : C, 59.62; H, 7.51; N, 11.60; O, 21.20; found: C,
30 45
5 8
59.66; H ,7.55; N, 11.54; O, 21.35%.
1,4,7-Tris(carboxymethyl)-10-(2-aminoethyl)-1,4,7,10-tetra-
azacyclododecane, 3. 3, an amino derivative, was prepared
from 2 (0.70 mmol) by treating with a mixture of 48% HBr
(100 mL) and glacial acetic acid (100 mL, pH D2.5È3.0); the
resulting mixture was reÑuxed for 12 h. After evaporation to
dryness the solid residue was treated with 1 M HBr (100 mL)
and the undissolved residue of phthalic acid was removed by
Ðltration. The Ðltrate was evaporated to dryness and
redissolved in hot 48% HBr (75 mL). On gradual addition of
glacial acetic acid (200 mL) to the stirred and ice-cooled solu-
tion the crude amine hydrobromide precipitated. It was col-
lected, washed thoroughly with ethanol and ether, and Ðnally
dried over P O at 1 mm Hg for several hours. The amino
NMR and mass spectrometry
NMR data were recorded on a Bruker AC 400 operating near
400 (1H) or 100 (13C) MHz or on a Bruker AC 200 operating
near 200 (1H) or 50 (13C) MHz. Chemical shifts were relative
4
10
derivative was dissolved in alkaline aqueous solution (pH 11)
with stirring at 60 ¡C for 4 h and the reaction was monitored
on HPLC. After the reaction was completed the pH was
adjusted to 6 using 6 M HCl and water was removed to
dryness. The obtained glassy solid was redissolved in 1 L of
water and the product was lyophilised. Yield 80%. Reversed-
to either HDO (4.70 ppm) or residual CHCl (7.24 ppm).
3
Mass spectra were obtained on a ZAB-HS-2F mass spectro-
meter (VG Analytical Instruments) at Veterinary Medical
College (Nantes, France) using DCI or EI mode and FAB`
mode. During mass spectrometry measurements, either 3-
nitrobenzyl alcohol or dithiothreitolÈdithioerythritol (3 : 1
w/w) was used as a matrix along with a small amount of p-
toluenesulfonic acid. FAB spectra contained polyethylene
glycol or polyethylene glycol methyl ether as references. Ele-
mental analyses were performed at Benaras Hindu University
(Varanasi, India).
phase C HPLC: solvent A: 0.1 M ammonium acetate, pH
18
6; solvent B: MeOH; 15È65% B, 0È25 min; 65È100% B,
30È35 min; 100È15% B, 35È40 min; product peak at 6 min.
FAB-MS: m/z calc. for [M ] H]` 390, found 390. 1H NMR
(D O): 2.92È3.43 (m, 20H, H-2, H-12, H-15 and H-16), 3.71È
2
3.73 (3s, 6H, H-13).
1,4,8-Tris(carboethoxymethyl)-1,4,8,11-tetraazacyclotetra-
decane, 4. The tri-N-substituted cyclam 4 was prepared by
adding 2.7 equiv. of ethyl bromoacetate to a solution of tetra-
azacyclotetradecane in dichloromethane with stirring at room
temperature for 48 h, yielding 74% tri-N-substituted product.
The remaining tetrasubstituted product was removed by Ðl-
tration at the end of the reaction. The resulting Ðltrate was
washed with water and puriÐed on a silica gel column by Ñash
chromatography (10% MeOHÈCH Cl ). FAB-MS: m/z calc.
Syntheses and spectroscopic data
1,4,7-Tris(carboethoxymethyl)-1,4,7,10-tetraazacyclododec-
ane, 1. 1 was prepared by adding 2.24 equiv. of ethyl bromo-
acetate dropwise (in D30 mL CH Cl ) to a CH Cl solution
2
2
2 2
of 1 equiv. tetraazacyclododecane; the resulting solution was
stirred at room temperature for 40 h and produced a mixture
of two products. The tetrasubstituted product was removed by
Ðltration; the resulting Ðltrate was washed with water and
dried over anhydrous Na SO , Ðltered, and evaporated under
2
2
for [M ] H]` 459, found 459. 1H NMR (400 MHz, CDCl ):
3
d 1.26 (2t, 9H), 1.69 (q, 2H), 2.06 (q, 2H), 2.63È3.54 (m, 22H),
2
4
reduced pressure. The crude product was puriÐed on a silica
gel open column by Ñash chromatography (10%
MeOHÈCH Cl ), yielding 72% of tri-N-substituted tetra-
4.15 (2 q, 6H), 10.01 (br, 1H). 13C NMR (CDCl ): d 14.6 (C-
3
18), 23.1 (C-13), 23.8 (C-6), 46.7, 47.6 (C-10, C-12), 48.9È54.3
(C-2 to C-5, C-7, C-9 and C-14), 54.4È55.4 (C-15), 60.7È61.2
(C-17), 171.5 (C-16b), 172.1 (C-16a, C-16c). EI-MS (% rel.
int.): m/z 458 (27), 385 (56), 371 (35), 273 (18), 199 (48), 173
(24), 130 (100) (see ESI for identity of fragment peaks).
2
2
azacyclododecane 1. FAB-MS: m/z calc. for [M ] H]` 431,
found 431. 1H NMR (250 MHz, CDCl ): d 1.25 (2t, 9H), 2.91
3
(m, 12H), 3.12 (m, 4H), 3.45 (2s, 6H), 4.16 (q, 6H), 10.01 (br,
1H). 13C NMR (CDCl ): d 14.6 (C-16), 47.7 (C-9, C-11), 49.7
3
(C-2 to C-6), 51.8 (C-8, C-12), 57.6 (C-13), 61.1 (C-15), 170.7
1,4,8-Tris(carboethoxymethyl)-11-[N-2-(ethyl)phthalimide]-
1,4,8,11-tetraazacyclotetradecane, 5. 5 was prepared from tri-
substituted 4 in the same way as compound 2 (yield 92%).
FAB-MS: m/z calc. for [M ] H]` 632, found 632. 1H NMR
(250 MHz, CDCl ): 1.26 (t, 9H, J \ 7.1), 1.61 (m, 4H),
(C14b), 171.5 (C-14a, C-14c). EI-MS (% rel. int.): m/z 430 (27),
357 (88), 314 (30), 300 (30), 288 (76), 271 (21), 259 (50), 185 (97),
173 (68), 159 (34), 144 (62), 130 (100) (see ESI for identity of
fragment peaks).
3
HvH
2.70È3.21 (m, 18H), 3.35È3.41 (3s, 6H), 3.62 (m, 2H), 4.13È4.16
(2q, 6H, J \ 7.1), 7.75 (dd, 2H, J \ 6.0 and J \ 3.1),
1,4,7-Tris(carboethoxymethyl)-10-[N-2-(ethyl)phthalimide]-
1,4,7,10-tetraazacyclododecane, 2. 2 was obtained by adding
an equivalent of N-(bromoethyl)phthalimide in acetonitrile to
a solution of 1 using 8 equiv. of Na CO in MeCN at 60È
HvH
HvH
HvH
HvH
7.89 (dd, 2H, J \ 6.0 and J \ 3.1 Hz). 13C NMR
HvH
(CDCl ): 14.1 (C-18), 22.8, 23.5 (C-6, C-13), 28.2 (C-19), 39.1È
3
55.6 (C-2 to C-5, C-7 to C-12, C-14, C-15, C-20), 60.8 (C-17),
2
3
70 ¡C for 12 h under N atmosphere. The reaction mixture
123.3 (C-23), 131.2 (C-22), 134.2 (C-24), 167.5 (C-21), 170.8È
2
was brought to room temperature, Ðltered, and evaporated
172.0 (C-16). Anal. calc. for C
N, 11.09; O, 20.26; found: C, 60.90; H, 7.85; N, 11.14; O,
20.21%.
H
N O : C, 60.84; H, 7.82;
32 49
5 8
under reduced pressure. The product was dissolved in chloro-
form and washed several times with 100 mL of water and the
organic phase was dried over magnesium sulfate, Ðltered and
evaporated to dryness, yielding 93% of 2. FAB-MS: m/z calc.
1,4,8-Tris(carboxymethyl)-11-(2-aminoethyl)-1,4,8,11-tetra-
azacyclotetradecane, 6. The aminoethyl derivative 6 was
obtained from an aqueous solution of 5 and subjected to
cleavage and hydrolysis in the same way as compound 3.
for [M ] H]` 604, found 604. 1H NMR (400 MHz, CDCl ):
3
d 1.27 and 1.30 (2t, 9H, J \ 7.1), 2.86È3.09 (m, 18H), 3.38È
HvH
3.46 (2s, 6H), 3.58 (t, 2H, J \ 6.7), 4.11 and 4.15 (2q, 6H,
HvH
J
\ 7.1) 7.72 (dd, 2H, J \ 3.1) 7.83 (dd, 2H, J \ 6.0
Reversed-phase C HPLC: solvent A: 0.1 M ammonium
HvH
HvH
HvH
18
New J. Chem., 2001, 25, 336È339
337