References and Notes
<A NAME="RG22506ST-1">1</A>
Rinck PA.
Magnetic Resonance in Medicine
Blackwell Scientific Publications;
Oxford, UK:
1993.
<A NAME="RG22506ST-2">2</A>
Merbach AE.
Tóth É.
The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging
John Wiley & Sons Ltd;
Chichester:
2001.
<A NAME="RG22506ST-3">3</A>
Caravan P.
Ellison JJ.
McMurry TJ.
Lauffer RB.
Chem. Rev.
1999,
99:
2293
<A NAME="RG22506ST-4">4</A>
Masotti A.
Mangiola A.
Sabatino G.
Maira G.
Denaro L.
Conti F.
Ortaggi G.
Capuani G.
Int. J. Immunopathol. Pharmacol.
2006,
19:
11
<A NAME="RG22506ST-5">5</A>
Reichert DE.
Lewis JS.
Anderson CJ.
Coord. Chem. Rev.
1999,
184:
3
<A NAME="RG22506ST-6">6</A>
Thunus L.
Lejeune R.
Coord. Chem. Rev.
1999,
184:
125
<A NAME="RG22506ST-7">7</A>
Lattuada L.
Lux G.
Tetrahedron Lett.
2003,
44:
3893
<A NAME="RG22506ST-8">8</A>
Kroft LJM.
de Roos A.
J. Magn. Reson. Imaging
1999,
10:
395
<A NAME="RG22506ST-9">9</A>
Bogdanov AA.
Lewin M.
Weissleder R.
Adv. Drug Deliv. Rev.
1999,
37:
279
<A NAME="RG22506ST-10">10</A>
Ladd DL.
Hollister R.
Peng X.
Wei D.
Wu G.
Delecki D.
Snow RA.
Toner JL.
Kellar K.
Eck J.
Desai VC.
Raymond G.
Kinter LB.
Desser TS.
Rubin DL.
Bioconjugate Chem.
1999,
10:
361
<A NAME="RG22506ST-11">11</A>
Krause W.
Hackmann-Schlichter N.
Maier FK.
Müller R.
Top. Curr. Chem.
2000,
210:
261
<A NAME="RG22506ST-12">12</A>
Glogard C.
Stensrud G.
Hovland R.
Fossheim SL.
Klaveness J.
Int. J. Pharm.
2002,
233:
131
<A NAME="RG22506ST-13">13</A>
Alhaique F.
Bertini I.
Fragai M.
Carafa M.
Luchinat C.
Parigi G.
Inorg. Chim. Acta
2002,
331:
151
<A NAME="RG22506ST-14">14</A>
Tournier H.
Hyacinthe R.
Schneider M.
Acad. Radiol.
2002,
9 (Suppl. 1):
S20
<A NAME="RG22506ST-15">15</A>
Glogard C.
Hovland R.
Fossheim SL.
Aasen AJ.
Klaveness J.
J. Chem. Soc., Perkin Trans. 2
2000,
1047
<A NAME="RG22506ST-16">16</A>
Anelli PL.
Lattuada L.
Lorusso V.
Schneider M.
Tournier H.
Uggeri F.
MAGMA
2001,
12:
114
<A NAME="RG22506ST-17">17</A>
Lauffer RB.
Chem. Rev.
1987,
87:
901
<A NAME="RG22506ST-18">18</A>
Gouin S.
Winnik FM.
Bioconjugate Chem.
2001,
12:
372
<A NAME="RG22506ST-19">19</A>
Hovland R.
Glogard C.
Aasen AJ.
Klaveness J.
Org. Biomol. Chem.
2003,
1:
644
<A NAME="RG22506ST-20">20</A>
Hovland R.
Aasen AJ.
Klaveness J.
Org. Biomol. Chem.
2003,
1:
1707
<A NAME="RG22506ST-21">21</A>
Compound 2: A solution of 1-bromododecane (20 g, 80 mmol) in EtOH (100 mL) was added over 1
h to a stirred solution of diethylentriamine 1 (8.25 g, 80 mmol) in EtOH (100 mL) at r.t. NaOH (0.1 M) was added to the reaction
mixture until the pH >7. The resulting solution was heated at 95 °C for 6 h, stirred
at r.t. for 18 h, and then the solvent was evaporated under reduced pressure. The
crude oil was purified by distillation collecting the fraction with a boiling point
of 265-270 °C, which furnished 2 as a transparent oil (9.46 g, 41%). 1H NMR (300 MHz, D2O): δ = 0.96 (CH3, t, 3 H), 1.37 (CH2, br, 18 H), 1.56 (CH2, m, 2 H), 2.51 (CH2N, t, 2 H), 2.73 (CH2N, t, 2 H), 2.83 (CH2N, br, 4 H), 2.87 (CH2N, t, 2 H). 13C NMR (300 MHz, D2O): δ = 13.41, 22.03, 26.88, 28.97, 29.19 (br m), 29.55, 31.28, 41.08, 48.73, 48.90,
49.40, 51.86. ESI-MS: m/z = 272.3 [M + H]+. Anal. Calcd for C16H37N3: C, 70.77; H, 13.74; N, 15.48. Found: C, 71.01; H, 13.93; N, 15.53. Compound 3: To a solution of 2 (2.7 g; 10 mmol) in THF (250 mL), was added bromoacetic acid (13.9 g, 0.1 mol, 10
equiv) in H2O (100 mL) over 2 h; the pH of the reaction mixture was maintained at 12 by the constant
addition of NaOH (0.1 M). The mixture was heated at 95 °C for 6 h, then the solvent
was evaporated under reduced pressure. The milky residue was treated with HCl until
the solution was pH 1 and the resulting acidic solution was filtered. The solid was
washed several times with cold EtOH and dissolved again in H2O (pH 8). The solution was treated with HCl until a precipitate formed. The white
solid was filtered, washed several times with cold H2O, and dried in a vacuum desiccator (1.1 g; 22%). 1H NMR (300 MHz, D2O): δ = 0.65 (CH3, t, 3 H), 1.04 (CH2, br, 20 H), 2.24 (CH2N, m, 2 H), 2.32 (CH2N, m, 8 H), 2.83 (CH2COOH, br, 8 H). 13C NMR (300 MHz, D2O): δ = 14.18, 22.77, 25.22, 27.82, 29.52, 29.80 (br m), 32.06, 51.18, 52.26, 52.65,
55.10, 58.46, 59.02, 59.41, 179.34. ESI-MS: m/z = 262.96 [M + Na]2+. Anal. Calcd for C24H45N3O8: C, 57.24; H, 9.01; N, 8.34. Found: C, 57.17; H, 9.24; N, 8.33. Compound 4: A solution of GdCl3·6H2O (0.148 g, 0.4 mmol) in H2O (20 mL) was added dropwise to a solution of 3 (0.2 g, 0.4 mmol) in H2O (100 mL) and NaOH (2 M, 5 mL); the pH of the reaction mixture was maintained at
12 by the constant addition of NaOH (2 M). After 6 h the solution was concentrated
to 25 mL and absolute EtOH (100 mL) was added. The precipitate was washed several
times with EtOH, filtered, and dried in vacuo to obtain the complex 4 as a white solid (0.12 g, 46%). ESI-MS: m/z = 219.20 [M + Gd]3+. Anal. Calcd for C24H41N3O8Gd·4H2O: C, 39.55; H, 6.78; N, 5.76. Found: C, 40.01; H, 6.93; N, 5.84.