Tipos de mecanismos de amparo

One of the most important considerations when performing HT experiments are which analytical methods are best to process such large volumes of data. To analyse and characterise materials which are synthesised through HT, it is important to avoid any time-consuming analysis which wouldn’t reveal anything significant. Infra-red (IR) measurements can indicate the presence of a functional group, for example, formation of an imine bond. However, IR rarely provides any direct structural information, which is of paramount importance for supramolecular systems, as it is not always clear what the reaction outcome is. For example, although IR data could indicate the formation of an imine bond with a sharp C=N stretch at 1656 - 1742 cm-1_, this wouldn’t be able to confirm whether the molecule synthesised was a cage or macrocycle, or whether the reaction had gone to completion.

Comparatively, nuclear magnetic resonance spectroscopy (NMR) can provide this information, and a 1_{H NMR would only take an average of 16} minutes, but the structure of the complex would need to be inferred from the NMR spectra. Solution-based NMR can be used to elucidate some structural information, however this can be limited by highly symmetrical materials.231_H NMR determines proton ‘environments’, showing a peak at the corresponding frequency of the nucleus. Therefore, in highly symmetrical molecules, the chemical environments can be determined but the relative structure would be difficult to accurately predict. In these cases, SCXRD can be used for accurate structural determination. It has been shown that for various isomers of fullerene, 13_{C NMR can be used for accurate identification however other} complimentary spectroscopic techniques were required for full confirmation.24

Solid state NMR, using magic angle spin (MAS) can be also be employed, rather than solution based in order to determine structural

100

information. This technique can be used to compliment X-ray data, as opposed to replacing it.25 _{Published in 2017 is an example of using kinetic solid state} NMR to show that tubular cages TCC2 and TCC3 could be used as molecular rotors.26 _{Furthermore, NMR can be used to show where in a solid structure} gases can occupy the cages, and henceforth preferential conditions for gas sorption.27 _{The Warmuth group has also published a number of organic cages,} which have all been characterised using 1D and 2D NMR, with conclusions verified by GPC and MALDI-TOF, as well as computational data.28–30

NMR is an incredibly useful spectroscopic tool for both crystalline and amorphous samples, particularly for kinetic or sorption studies. Nonetheless, we showed in Chapter 2 that it was not possible to determine between

TCC1[3+6] and TCC1[6+12] using 1_{H NMR.}31 _{Mastalerz group synthesised a large} organic cage, with the main information obtained from the 1_{H NMR spectra} that the cage had formed the correct stoichiometry, 2:3, and the predicted symmetry of the reaction product.32 _{Other cage structures have also relied} heavily on crystal structures when they have the same stoichiometric ratio to determine the difference between the two different products.33

Interpreting NMR data can be challenging, particularly when assessing more complex structures such as interlocked cages.34 _{Interlocked structures} can prove challenging to analyse by NMR data, due to the interactions through space, which can cause shielding and, hence, change the frequency of the chemical shifts.35 _{Previous studies into interlocked systems have used other} methods for the identification of these interlocked species, predominantly crystallography, and NMR as a tool for verification.36

Examples of utilising NMR for structural identification include the ‘Star of David’ catenane, which relied heavily on the X-ray crystal structure, as well as comparing the NMR spectra of the starting materials and partially reacted reagents.37 _{Interlocked cages are also reliant on 2D NMR, for example} Heteronuclear single-quantum correlation spectroscopy (HSQC). A triply interlocked covalent cage, involving two equivalents of Covalent Cage 1 (CC1) utilised 2D NMR spectroscopy to provide further information of the through- space interactions between the two cages.38 _{Fujita et al. also demonstrated}

101

NMR as a useful tool to follow an interlocking reaction, however an X-ray structure was again required in order to determine the structure accurately.39

These limitations of NMR for determining the structure mean other approaches need to be considered. Currently, there are existing methods which can be used which involve minimal human-interactions and rely on robotics and software to solve crystal structures. Synchotrons can be used for high-throughput studies, with fast collection times and high energy X-rays, enabling better data collections for smaller crystals.40 _{Current technology at} Diamond Light Source (DLS) is introducing automated sample changing of crystals using robotics and single crystals cooled in N2.41–44

In order to get a complete picture of the atomic structure for supramolecular complexes, the most efficient and accurate method is to use (SCXRD). However, crystallography can be a time-consuming process, as is requires the growth of a single crystal. Single crystal growth can take anything from days to weeks, and is dependent on two important factors in crystallisations; nucleation and crystal growth.45 _{The two are independent of} one another, but crystal growth is reliant on nucleation.46,47 _{Nucleation is reliant} on a number of conditions such as temperature, the concentration of the solution, or the presence of impurities as nucleation is a thermodynamic process.48 _{Once nucleation has occurred, crystal growth can follow, as the} nuclei agglomerate and form a larger crystalline structure.49

As the intermolecular interactions between POCs are non-covalent, they are non-directional and weaker than directional covalent organic or metal- organics used to synthesise other porous molecular materials, crystal growth can also be challenging.50,51 _{A recent study has shown that crystal growth of}

CC3 was dependent upon the synthesis time, as shown in Figure 1.52 _{In this} particular case, three distinct growth stages were identified; 1) rapid crystal growth stage favoured by slow synthesis times; 2) intermediate synthesis times resulted in increased amounts of crystal fragmentation and redissolution; and finally, 3) with longer synthesis times regrowth begins and larger crystals can be found again which corresponds to Ostwald ripening.53

102

This study has highlighted the impact that one variable, synthesis time, has on the crystal growth of one particular POC. However, this material, by comparison to other POCs, has a relatively short growth time (approximately 4 days), whereas some systems can take weeks or even longer. For microcrystalline materials, PXRD can be employed, however for SCXRD a larger crystal is required.54 _{Therefore, the main limit to obtain a single crystal} structure, is the growth of a well-ordered single crystal which is large enough for a data collection, producing an accurate model.

Figure 1 Chart showing the effect synthesis time has on the crystal growth of CC3, indicating the optimal synthetic time for large crystals is 18 hours.

Reprinted with permission from J. Lucero et al., Cryst. Growth Des., 2018, 18, 921–927. Copyright 2018 American Chemical Society.