Impact of Varying the Phenylboronic Acid Position within Macrocyclic Eu(III) Complexes on the Recognition of Adenosine Monophosphate

The selective recognition of anions in water by artificial receptors remains a significant research challenge. The creation of a receptor selective for adenosine monophosphate (AMP) is particularly difficult due to...

The aqueous phase was extracted with dichloromethane (3 × 10 mL) and the combined organic phases were dried (MgSO4), filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (silica gel; 20 -60% EtOAc/petroleum ether) to give the desired aldehyde 2 (1.00 g, 89%) as an off-white solid. 1

8-((2-Iodobenzyl)oxy)quinolin-2-yl)methanol (3o)
To a solution of aldehyde 2o (0.500 g, 1.28 mmol) in methanol (20 mL), was added sodium borohydride (0.150 g, 3.85 mmol) and the reaction mixture was stirred at 40 °C for 24 hours. The reaction was quenched with deionised water (3 mL) and the solvent was removed under reduced pressure. The crude material was partitioned between dichloromethane (20 mL) and saturated sodium chloride solution (10 mL). The aqueous layer was extracted with dichloromethane (3 × 15 mL) and the organic layers were combined, dried (MgSO4) and concentrated under reduced pressure to give the desired alcohol 5 (0.490 g, 98%) as a white solid. 1 To a solution of alcohol 3o (100 mg, 256 µmol) and triethylamine (54 mL, 384 µmol) in anhydrous acetonitrile (5 mL) was added methanesulfonyl chloride (22 mL, 282 mmol). The resulting orange reaction mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane (10 mL) and saturated sodium chloride solution (10 mL). The aqueous layer was extracted with dichloromethane (3 × 15 mL) and the organic layers were combined, dried (MgSO4), filtered and evaporated under reduced pressure to give the desired mesylate ester 4o (118 mg, 98%) as a yellow oil, which was used immediately in the next step. 1

8-((4-Iodobenzyl)oxy)quinoline-2-carbaldehyde (2p)
To a solution of 1 (0.500 g, 2.89 mmol) and potassium carbonate (0.599 g, 4.33 mmol) in anhydrous acetonitrile (15 mL) was added 4-iodobenzyl bromide (1.03 g, 2.95 mmol). The reaction mixture was stirred at room temperature for 24 hours. The resulting orange solution was centrifugated at 120 rpm for 3 minutes. The solution was decanted, and the solid pellet was washed twice with dichloromethane (3 × 15 mL). The solvent was evaporated under reduced pressure and the resulting residue was partitioned between dichloromethane and saturated aqueous sodium chloride. The aqueous phase was extracted with dichloromethane (3 × 10 mL) and the combined organic layers were dried (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (silica gel; 25 -60% EtOAc/petroleum ether) to give the desired compound 2p as a white solid (1.01 g, 82%). 1

(8-((4-Iodobenzyl)oxy)quinolin-2-yl)methanol (3p)
To a solution of aldehyde 3p (0.500 g, 1.28 mmol) in methanol (20 mL), was added sodium borohydride (60 mg, 1.60 mmol) and the reaction mixture was stirred at 30 °C for 24 hours. The solvent was removed under reduced pressure and the resulting residue was partitioned between dichloromethane (20 mL) and saturated aqueous sodium chloride (10 S7 mL). The aqueous layer was extracted with dichloromethane (3 × 20 mL) and the organic layers were combined, dried (MgSO4) and concentrated under reduced pressure to give the desired alcohol 7 as a white solid (0.445 g, 89%). 1 13   To a solution of alcohol 3p (100 mg, 0.26 mmol) and triethylamine (55 mL, 0.38 mmol) in anhydrous acetonitrile (5 mL) was added methanesulfonyl chloride (22 mL, 0.28 mmol) and the orange mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure and the residue was partitioned between dichloromethane (15 mL) and saturated aqueous sodium chloride (10 mL). The aqueous layer was extracted with dichloromethane (3 × 10 mL) and the organic layers were combined, dried (MgSO4) and concentrated under reduced pressure to give mesylate ester 4p as a yellow solid (103 mg, 85%), which was used immediately in the next step.

[Eu.pI][Cl]
The deprotected ligand 5p (20 mg, 30 µmol) was dissolved in water (5 mL) and the pH adjusted to pH 7.5 using 0.3 M NaOH solution. EuCl3.6H2O (11 mg, 30 µmol) was added and the pH was readjusted to 7.5. The solution was stirred at S8 95%) as a yellow solid, which was used in the next step without further purification.