# Characterization of Sequence Distributions in Random and Semi-Random Copolymers

## TL;DR

The paper introduces a method to distinguish sequence distributions in random and semi-random copolymers using selective digestion and analysis techniques.

## Contribution

A novel strategy for characterizing copolymer sequences through cleavage and analysis, validated by simulations and experiments.

## Key findings

- P-S copolymers show broader and bimodal fragment distributions compared to random copolymers.
- Monte Carlo simulations align with experimental data, confirming the influence of feed ratios and dispersity.
- The method enables encoding and detecting distinct microstructural features in degradable polyesters.

## Abstract

We report a strategy for analyzing and distinguishing the sequence distributions of random and semirandom poly­(lactic-co-glycolic acid) (PLGA) analogs using selective digestion at cleavable olefin-containing monomer units. Semirandom copolymers were synthesized via a parallel-successive (P-S) approach that enables coarse-grained sequence control by coupling telechelic oligomers of varied composition and length. Following cross-metathesis digestion, the resulting fragment distributions were fractionated and analyzed via NMR, SEC, and MALDI-MS. These postdigestion data directly reflect the microstructural arrangement of the cleavable units in the predigestion copolymers. Monte Carlo simulations were employed to model both random and P-S copolymerizations, offering in silico digestion data that elucidate the influence of oligomer feed ratios and dispersity on the resulting block-length distributions. Experimental and simulated results demonstrate that P-S copolymers exhibit broader and sometimes bimodal fragment distributions compared to their random analogs, validating the method’s capacity to encode and detect distinct microstructural features. This approach provides a scalable, analytically tractable platform for tuning and characterizing sequence distributions in degradable polyesters and potentially other polymer systems where sequence plays a critical role in material properties.