TABLE 2.

Techniques and their analytical strengths and weaknesses in the context of analysing CDSA structures and intermediates.

Technique	Sample type	Strength	Weakness
NMR	Liquid, solid	Can measure intermolecular environments	Relies on presence of spin active nuclei
		Can be applied dynamically	Overlapping signals present assignment challenges
		Certain methods, e.g NOESY, can provide intermolecular structural information	Difficulties with radicals
DOSY NMR	Liquid, solution	Excellent for determining size of molecules within mixtures.	Relies on presence of spin active nuclei
		Can be layered over other NMR experiments.	Can struggle with larger molecules that diffuse slowly Can be affected by exchange processes
DLS	Solution or suspension	Can accurately measure the size and shape of macromolecules and supramolecules	Struggles to discern structurally similar molecules (monomers, dimers)
		Can study interactions between analytes	Structures formed in short timescale obscured by larger ones
TEM	Ultrathin solid	Allows direct structural characterisation	Samples must be “electron transparent”
			Sample preparation can be challenging
			Not dynamic
TGA	Solid or liquid	Can give insight into the thermodynamic driving forces of self- assembly	Structural information obtained is limited
UV-Vis spectroscopy	Solution	Effective for measuring transition elements and conjugated organic molecules	Limited available structural information
		Characteristic absorbances reveal (supra)molecular changes	All molecules in solution can give signal, leading to overlapping signals
		Fast measurement allows dynamic measurements and reaction monitoring	Target species must be spectroscopically active
ITC	Solution	Quantitative measure of binding affinities and thermodynamics	Measures equilibrium conditions, not suited to non-equilibrium systems
			Cannot distinguish individual components from less specific contributions of bulk solution
X-ray Crystallography	Crystalline solid	Can obtain full structure, including isomerism	Dependant on successful crystallisation
		Self-assembled structures can be preserved in crystal	Does not capture dynamic process
		Information about bonding
ESI-MS or MALDI-MS	Solid, liquid, gas	Empirical formulas and charge states easily distinguished	Target species must be ionisable/carry a charge
		Structural information through MSn	Artifacts due to ionisation process
		Time scale dynamic range (milliseconds – hours) allows for dynamics and reaction monitoring	Cannot decern all isomers
		Dynamic range of masses allows simultaneous monitoring of reactant and product	Isobaric interferences
		Fragile species can be detected
		Can be automated, high throughput
IMS	Solid, liquid, gas	In addition to advantages for MS, can filter isomers and isobars	Target species must be ionisable/carry a charge
		Structural identification via collisional cross section (Ω or CCS)	Fragile species can be fragmented