Diffusion process of amino acids in polymer supports for solid‐phase peptide synthesis as studied by pulsed‐field‐gradient spin‐echo proton nuclear magnetic resonance

The diffusion coefficient (D) values oftert‐butyloxycarbonyl‐glycine,tert‐butyloxycarbonyl‐L‐tryptophan,tert‐butyloxycarbonyl‐L‐phenylalanine (Boc‐Phe), and 9‐fluorenylmethoxycarbonyl‐L‐phenylalanine in Merrifield polystyrene (MPS) gels, poly(ethylene glycol)‐grafted polystyrene (PEG–PS) gels, and crosslinked ethoxylate acrylate (CLEAR) gels, as used in solid‐phase peptide synthesis, were determined by the pulsed‐field‐gradient spin‐echo1H‐NMR method. From these experimental results, it was found that the amino acids in MPS gels, PEG–PS gels, and CLEAR gels withN,N‐dimethylformamide‐d7(DMF‐d7) as a solvent had multidiffusion components within a measurement timescale of 10 ms. TheDvalue of Boc‐Phe in polystyrene gels (1% divinylbenzene crosslinked) with tetrahydrofuran‐d8was much larger than that in the same gels with DMF‐d7. Furthermore, the required time in which an amino acid transferred from a reactive site to a reactive site was estimated, within which the solvents and amino acids in the polymer supports diffused in the swollen beads.