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 |