References and Notes
For recent reviews on MRI CAs, see:
1a
Yoo B.
Pagel MD.
Front. Biosci.
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Geraldes CFGC.
Laurent S.
Contrast
Med. Mol. Imaging
2009,
4:
1
1c
Terreno E.
Delli Castelli D.
Viale A.
Aime S.
Chem. Rev.
2010,
110:
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2 For a recent review on PET CAs, see: Wadas TJ.
Wong EH.
Weisman GR.
Anderson CJ.
Chem. Rev.
2010,
110:
2858
3 For a recent review on synthesis
of functionalized cyclens, see: Suchý M.
Hudson RHE.
Eur. J.
Org. Chem.
2008,
4847
For recent reviews, see:
4a
Mewis RE.
Archibald SJ.
Coord.
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4b
De León-Rodríguez LM.
Kovács Z.
Bioconjugate
Chem.
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391
PARACEST (PARAmagnetic Chemical
Exchange Saturation Transfer) MRI CAs represent a new group of MRI
CAs developed based on the original idea presented in:
5a
Ward KM.
Aletras AH.
Balaban RS.
J. Magn. Reson.
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143:
79
For recent reviews on PARACEST MRI CAs, see:
5b
Terreno E.
Castelli DD.
Aime S.
Contrast
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2010,
5:
78
5c
Viswanathan S.
Kovács Z.
Green KN.
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Li AX.
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Jones CK.
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Li AX.
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Suchý M.
Li AX.
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RHE.
Contrast Med. Mol. Imaging
2012, DOI:
10.1002/cmmi.1461
8
General Experimental
Procedures: All amino acids (naturally occurring l-isomers)
and reagents were commercially available, unless otherwise stated.
All solvents were HPLC grade and used as such, except for H2O (18.2
MΩ˙cm-¹ Millipore
water). Organic extracts were dried with Na2SO4 and
solvents were removed under reduced pressure in a rotary evaporator.
Aqueous solutions were lyophilized. Flash column chromatography
(FCC) was carried out using silica gel, mesh size 230-400 Å.
Thin layer chromatography (TLC) was carried out on Al-backed silica gel
plates, compounds were visualized by UV light or I2 vapors.
HPLC analysis and purification were done using a Delta-Pak C18 300 Å column
(particle size 15 µm; 8 × 100 mm Radial-Pak cartridge).
Mobile phase: method A: 90% H2O-10% MeCN → 50% H2O-50% MeCN
over 9 min (compounds 7a, 7b, 11a and 11b);
method B: 90% H2O-10% MeCN → 59% H2O-41% MeCN
over 7 min, fractions containing an impure material were concentrated
and subjected to the purification using method C: 99% H2O-1% MeCN → 89% H2O-11% MeCN
over 11 min (compounds 10a and 10b). Linear gradient and flow rate 3 mL/min
was used in all the methods listed above. Ultra performance liquid
chromatography (UPLC) was performed using a BEH C18 column (particle
size 1.7 µm; 2.1 id × 50 mm) with an inline mass
detector. Mobile phase: method D: 100% H2O → 25% H2O-75% MeCN
over 3 min, linear gradient, flow rate 0.25 mL/min. NMR
spectra were recorded on 400 MHz spectrometer; δ values
were referenced as follows DMSO-d
6 (2.49
ppm) for ¹H NMR (400 MHz) and DMSO-d
6 (39.5 ppm) for ¹³C
NMR (100 MHz). Mass spectra (MS) were obtained using an electron
spray ionization (ESI) Time-of-Flight (TOF) instrument.
9 Supporting Information: General considerations
and experimental procedures for the preparation of compounds 9a, 9b, 10a, 10b, 11a and 11b; ¹H
NMR spectra of compounds 7a, 7b, 9a, 9b, 10a, 10b, 11a and 11b; ¹³C NMR spectra
of compounds 9a and 9b;
high resolution (ESI) mass spectra of compounds 7a, 7b, 10a, 10b, 11a and 11b.
10
Tei L.
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Brücher E.
Cassino C.
Demicheli F.
Masciocchi N.
Giovenzana GB.
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11a
Hoigebazar L.
Jeong JM.
Choi SY.
Choi JY.
Shetty D.
Lee YS.
Lee DS.
Chung JK.
Lee MC.
Chung YK.
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Med. Chem.
2010,
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11b
Shetty D.
Jeong JM.
Ju CH.
Kim YJ.
Lee JY.
Lee YS.
Lee DS.
Chung JK.
Lee MC.
Bioorg.
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11c
Shetty D.
Choi SY.
Jeong JM.
Hoigebazar L.
Lee YS.
Lee DS.
Chung JK.
Lee MC.
Chung YK.
Eur.
J. Inorg. Chem.
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5432
11d
de Sá A.
Matias A.
Prata IM.
Geraldes CFGC.
Ferreira PMT.
André JP.
Bioorg. Med. Chem. Lett.
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12
Tolmachev V.
Altai M.
Sandström M.
Perols A.
Karlström AE.
Boschetti F.
Orlova A.
Bioconjugate Chem.
2011,
22:
894
13
Alkylation of
TACN (7a) with
N
-Chloroacetyl-Gly-Arg(NO
2
)-OMe (3a) and
N
-Chloroacetyl-Arg(NO
2
)-OMe (4a),
a Representative Experimental Procedure:
N-chloroacetyl-Gly-Arg(NO2)-OMe
(3a; 139 mg, 0.38 mmol) and N-chloroacetyl-Arg(NO2)-OMe
(4a; 117 mg, 0.38 mmol) and were added
to separate solutions of TACN (7a; 16 mg,
0.13 mmol) and DIPEA (66 µL, 0.38 mmol) in MeCN (1.8 mL)
and DMF (200 µL). The mixtures were stirred for 24 h at
70 ˚C, MeCN was evaporated, the residues were dissolved
in MeOH-H2O (1.5 mL each) and were subjected
to semi-preparative HPLC purification. The fractions containing
the products were concentrated to afford the products as colorless
solids. NOTAM-Gly-Arg(NO2)-OMe (7b):
yield: 104 mg (74%). HPLC (method A): t
R = 5.5
min. ¹H NMR (DMSO-d
6): δ = 8.46
(br s, D2O exch., 5 H), 7.91 (br s, D2O exch.,
5 H), 4.27 (m, 3 H), 3.80 (m, 6 H), 3.62 (m, 15 H), 3.09 (m, 18
H), 1.61 (m, 12 H). HRMS (ESI): m/z [M + H]+ calcd
for C39H70N21O18: 1120.5208;
found: 1120.5176. NOTAM-Arg(NO2)-OMe (7c):
yield: 87 mg (73%). HPLC (method A): t
R = 5.6
min. ¹H NMR (DMSO-d
6): δ = 8.56
(br m, D2O exch., 6 H), 7.91 (br s, D2O exch.,
6 H), 4.29 (m, 3 H), 3.63 (s, 9 H), 3.59 (m, 6 H), 3.03 (m, 18 H),
1.64 (m, 12 H). HRMS (ESI): m/z [M + H]+ calcd
for C33H61N18O15: 949.4564;
found: 949.4559.
14
Tamanini E.
Flavin K.
Motevalli M.
Piperno S.
Gheber LA.
Todd MH.
Watkinson M.
Inorg.
Chem.
2010,
49:
3489
15 Initial attempts to metallate 7b and 7c under
the previously established reaction conditions of heating an aqueous solution
of Ga(NO3)3 at pH 3 (ref. 11) showed the reaction
to be sluggish. After 18 h of reaction, the metallation was found to
be ca. 10% complete by UPLC HRMS analysis. Considering
the short half-lives of some radioactive isotopes of gallium, further
optimization of the reaction conditions is mandated.
