Fig. 5: Post ClickZip synthesis.
From: Ultra-inert lanthanide chelates as mass tags for multiplexed bioanalysis
Demonstration of the high robustness of ClickZip chelates with possible derivatization of its core or surface. No leak of LnIII ion was observed during any of these transformations. Yields refer to isolated compounds (except for the case of BocCys{Lu} where conversion is given instead). A Examples of core modifications (full structures). In addition to their unusually high stability in strong acids, ClickZip chelates can withstand other harsh conditions, even when its {Ln} core undergoes chemical transformation. Prolonged heating of Ph{Lu} with the excess ( > 30 equiv.) of strong base DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in D2O allowed exchange of all acidic carbon-bound hydrogen atoms for deuterium ( > 95% H to D exchange after single evaporation/D2O resupply cycle) without loss of the LuIII ions. Similarly, when a large excess of strong reducing agent ( > 1000 equiv. of NaBH4) was applied to Ph{Lu} in MeOH, quantitative reduction of one of the pyridine rings was achieved, yet no LuIII ions were found to escape from the cage during the process. B Examples of surface modifications (symbol structures). The ClickZip core is so benign that its presence can be ignored when performing surface modifications. For example, the Cl{Ln} was found to be a versatile precursor for the introduction of a wide range of functional groups (COOH, NH2, N3 and amino-acid) onto the ClickZip chelate, though it showed unexpected de-chlorination in presence of formate, which should be avoided (Supplementary Fig. 23). Conditions: (i) 4-(carboxymethyl)phenylboronic acid pinacol ester, XPhos Pd G2 (cat.), K3PO4, DMF, H2O, 80 °C; (ii) N-Boc-cysteine, DIPEA, DMSO, RT; (iii) NaN3, DMSO, 80 °C; (iv) propargyl amine, CuSO4 (cat.), sodium ascorbate, MES/NaOH buffer (pH = 5.2), H2O, RT; (v) 2-(4-boronophenyl)acetic acid, XPhos Pd G2 (cat.), K3PO4, DMF, H2O, 80 °C.
