Investigation of Parameters that Affect Resin Swelling in Green Solvents

Abstract

The influence of various physical and chemical factors on the swelling of polystyrene and PEG based resins in greener organic solvents has been systematically investigated. In general, chemical factors: the nature of the functionality/linker and the degree of loading were found to have a far larger influence on the swelling of the resins than physical parameters such as bead size. The results are interpreted in terms of Hansen solubility parameters for the solvents and there is evidence that some solvents interact with the polymeric core of a resin whilst others interact with the functionality. The results are extended to a study of the changes in resin swelling observed during both deprotection and chain elongation reactions during solid phase peptide synthesis.

Harnessing polarity and viscosity to identify green binary solvent mixtures as viable alternatives to DMF in solid-phase peptide synthesis

“…resin loading, cross-link density, mesh size, molecular and supramolecular properties of resin-loaded peptide, as well as the type of sidechain protection groups. 54 Nevertheless, the peptidyl resin generally showed reduced swelling compared to its corresponding starting resin and this phenomenon became more pronounced with increasing peptide length. The swelling propensity and response characteristics of the shortest and longest tested resinbound peptides (8-mer Octreotide-2-CTR and 58-mer Aprotinin-Wang respectively) in selected neat solvents and binary mixtures is illustrated in Fig.…”

“…To this end, several research groups have recently reported resin swelling experiments and SPPS using various alternative green solvents and their binary mixtures. 11,22,38,[54][55][56][57] In particular, Magtaan et al demonstrated correlation between volumetric and optical microscopybased methods on a range of resins using green solvents to aid the selection of suitable resin-solvent combinations. 57 Moreover, Ran et al used the Hansen solubility parameter in practice (HSPiP) software for predicting the resin swelling capacity in various green solvents and reported that binary mixtures of green solvents not only exceeded the performance of their individual component but also could be judiciously fine-tuned to mimic the swelling properties of DMF.…”

Flow-Based Fmoc-SPPS Preparation and SAR Study of Cathelicidin-PY Reveals Selective Antimicrobial Activity

“…However, upon continuing the synthesis to cathelicidin-PY 10−29 and to completion, the RP-HPLC chromatogram became increasingly complex, failing to afford the final 29-mer ( Figure 3 b,c). The high substitution resin (1.26 mmolg −1 ) may have contributed to steric hinderance and intra- and intermolecular aggregation, ultimately resulting in the failed synthesis [ 48 ]. Somewhat surprised by this failure, we attempted automated synthesis at room temperature with increased coupling times from 5 min to 1 h and otherwise identical conditions ( Scheme 1 b).…”

“…With the need to perform an additional synthetic step (disulfide cyclisation) and the desire to prepare multiple analogues, we were unsatisfied with this result. We speculated that the poor performance of both microwave and room temperature synthesis could be attributed to the high resin substitution rate of the relatively poor swelling 1% DVB cross-linked PS resin [ 48 ]. Thus, AM-PS (1.26 mmolg −1 ) resin was substituted for polyethylene glycol (PEG) grafted resin, TentaGel HL NH 2 resin, which has greater swelling capacity and is loaded at a lower substitution rate (0.48 mmolg −1 ).…”

In situ Fmoc removal – a sustainable solid-phase peptide synthesis approach

“…Given the definition of green chemistry by Paul Anastas in 1991, “Green Chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances”, 9 many academic and industrial groups have studied the replacement of N , N ′-dimethylformamide (DMF) and N -methylpyrrolidone (NMP), solvents of choice in SPPS, by green solvents. 10–23 However, few efforts have been devoted to solvent reduction by this strategy.…”