TY - JOUR
T1 - Solid-phase synthesis and evaluation of tumour-targeting phenylboronate-based MRI contrast agents
AU - Martinelli, Jonathan
AU - Jiménez-Juárez, Rogelio
AU - Alberti, Diego
AU - Geninatti Crich, Simonetta
AU - Djanashvili, Kristina
PY - 2020
Y1 - 2020
N2 - Paramagnetic macrocycles functionalized with phenylboronic moieties have proven to be interesting for MRI applications based on their ability to recognize cancer cells and generate local contrast. However, full use of the potential of this class of compounds is hampered by laborious and inefficient synthetic and, especially, purification procedures. The amphiphilic character of water-soluble phenylboronates renders them difficult compounds to be prepared through conventional solution synthesis due to the tendency to aggregate and form adducts with other nucleophiles. The new strategy described herein exploits the advantage of solid-phase synthesis with the application of DEAM-PS resin for anchorage and the subsequent simplified derivatization of boronates. GdDOTA-EN-PBA and its fluorinated analogue GdDOTA-EN-F2PBA were synthesized in a much easier, faster and economically convenient way to achieve good yields and purity. Furthermore, the effect of electron-withdrawing fluorine atoms on the aromatic ring of the latter compound was investigated by comparing the physico-chemical properties of both compounds as well as their binding affinity towards melanoma cancer cells.
AB - Paramagnetic macrocycles functionalized with phenylboronic moieties have proven to be interesting for MRI applications based on their ability to recognize cancer cells and generate local contrast. However, full use of the potential of this class of compounds is hampered by laborious and inefficient synthetic and, especially, purification procedures. The amphiphilic character of water-soluble phenylboronates renders them difficult compounds to be prepared through conventional solution synthesis due to the tendency to aggregate and form adducts with other nucleophiles. The new strategy described herein exploits the advantage of solid-phase synthesis with the application of DEAM-PS resin for anchorage and the subsequent simplified derivatization of boronates. GdDOTA-EN-PBA and its fluorinated analogue GdDOTA-EN-F2PBA were synthesized in a much easier, faster and economically convenient way to achieve good yields and purity. Furthermore, the effect of electron-withdrawing fluorine atoms on the aromatic ring of the latter compound was investigated by comparing the physico-chemical properties of both compounds as well as their binding affinity towards melanoma cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=85092944628&partnerID=8YFLogxK
U2 - 10.1039/d0ob01552k
DO - 10.1039/d0ob01552k
M3 - Article
C2 - 33000853
AN - SCOPUS:85092944628
SN - 1477-0520
VL - 18
SP - 7899
EP - 7906
JO - Organic & Biomolecular Chemistry
JF - Organic & Biomolecular Chemistry
IS - 39
ER -