Method development in interaction polymer chromatography

Highlights

• IPC methods can determine the chemical composition distribution of macromolecules.

• A large variety of IPC techniques are currently available (GPEC, TGIC, LCCC, etc.).

• Principles of operation and rational method development are explored here.

Abstract

Interaction polymer chromatography (IPC) is an umbrella term covering a large variety of primarily enthalpically-dominated macromolecular separation methods. These include temperature-gradient interaction chromatography, interactive gradient polymer elution chromatography (GPEC), barrier methods, etc. Also included are methods such as liquid chromatography at the critical conditions and GPEC in traditional precipitation-redissolution mode. IPC techniques are employed to determine the chemical composition distribution of copolymers, to separate multicomponent polymeric samples according to their chemical constituents, to determine the tacticity and end-group distribution of polymers, and to determine the chemical composition and molar mass distributions of select blocks in block copolymers. These are all properties which greatly affect the processing and end-use behavior of macromolecules. While extremely powerful, IPC methods are rarely employed outside academic and select industrial laboratories. This is generally because most published methods are “bespoke” ones, applicable only to the particular polymer being examined; as such, potential practitioners are faced with a lack of inductive information regarding how to develop IPC separations in non-empirical fashion. The aim of the present review is to distill from the literature and the author's experience the necessary fundamental macromolecular and chromatographic information so that those interested in doing so may develop IPC methods for their particular analytes of interest, regardless of what these analytes may be, with as little trial-and-error as possible. While much remains to be determined in this area, especially, for most techniques, as regards the role of temperature and how to fine-tune this critical parameter, and while a need for IPC columns designed specifically for large-molecule separations remains apparent, it is hoped that the present review will help place IPC methods in the hands of a more general, yet simultaneously more applied audience.

Introduction

A quick look around us should suffice to demonstrate that polymers, both natural and synthetic, form an integral part of our existence. From providing comfort (e.g., polyurethane foam cushions, cotton and nylon clothing) and safety (e.g., poly(vinyl butyral) interlayer for windshields and hurricane-resistant windows) to their roles in life-saving technologies e.g., acrylate copolymers in nonbiodegradable stent coatings and lactic acid copolymers in biodegradable ones, silicone or polyurethane-based shunts), polymers and polymeric-based materials are ubiquitous and our reliance upon them continues to increase.

To characterize the distribution of chain lengths, and accompanying molar mass distribution (MMD), of polymers, size-exclusion chromatography (SEC) has emerged over the last half-century as the premier method by which to do so [[1], [2], [3], [4]]. Coupled to a variety and, oftentimes, multiplicity of detection methods, SEC has also shown itself capable of providing information related to average changes in branching, chemical composition, sequence length, and conformation as a function of molar mass (M). For polymers not amenable to SEC analysis because of their large size and concomitant chain fragility, other, gentler techniques have emerged to fill the void, such as hydrodynamic chromatography (HDC) and flow field-flow fractionation (FlFFF) [[5], [6], [7]]. All these so-called size-based methods (SEC, HDC, FlFFF) possess the commonality of separating analytes by their size in solution, i.e., by differences in the hydrodynamic or solvodynamic volume of macromolecules at a given set of solvent and temperature conditions. This commonality is also responsible for one of the shortfalls of size-based methods: Within a given sample, analytes which differ from each other in topology (architecture – e.g., branching – or conformation) or in chemical composition (monomeric ratio or monomeric sequence) can occupy the same hydrodynamic volume as each other, resulting in their coelution within a given separation slice.

Addressing the aforementioned shortcomings of the size-based methods, in which separation is primarily entropy-controlled, is a group of techniques which fall under the umbrella term Interaction Polymer Chromatography (IPC) and in which separation is primarily driven by enthalpic forces. These techniques, which include methods such as gradient polymer elution chromatography (GPEC, both traditional and interactive), solvent gradient interaction chromatography (SGIC), temperature gradient interaction chromatography (TGIC), and various so-called “barrier” methods, have the ability to separate polymers according to chemical composition, inter alia. They can thus provide, on their own, the chemical composition distribution (CCD) of copolymers and, as the first dimension in a two-dimensional liquid chromatography (2D-LC) set-up with SEC as the second dimension, the combined CCD × MMD of copolymers and blends (henceforth, when SEC is mentioned other size-based methods are implied, unless otherwise noted).

It is these IPC techniques which are the topic of this review. We examine here their mechanisms of separation and their limitations and focus primarily on rational approaches to method development in IPC. It is the latter, especially, that has suffered from a dearth of information. Published methods appear to be mostly “bespoke,” i.e., developed for a particular sample, primarily using empirical approaches with limited, if any, inductive value to those attempting to adapt the methods to, or to design protocols for, polymers other than the specific ones discussed in a particular publication. Those fundamental books which have been published on the topic [[8], [9], [10], [11]], while an invaluable addition to any polymer chromatographer's library, are both out-of-print and quite dated as regards examples and current developments.

We include here a discussion of SEC “gradient” methods, part of the family of “barrier” techniques and a relatively novel addition to the IPC family. We discuss also liquid chromatography at the critical condition (LCCC), a technique which capitalizes upon the possibility of a balance between entropic and enthalpic forces during a separation, and which yields compositional information akin to that obtained via the enthalpically-dominated IPC methods.

For readers interested in the historical development of the various macromolecular separation techniques, development of SEC is covered in chapter 1 of [1] and in Ref. [4], of HDC in Ref. [6], and of flow and related FFF methods in Refs. [12]. As regards IPC, a nice, recent introduction can be found in Ref. [13]; more details regarding development primacy of the various IPC methods can be found in several of the book chapters by Berek, most notably in Refs. [14].