**4. Strategies to identify and achieve polymorphs and the influence on their properties**

#### **4.1 Identification of polymorphs**

The identification of polymorphism had been, in the vast majority of cases, a matter of chance, but this all changed as a result of the efforts of many scientists in the field. The first tool of recognition was visual observation inasmuch as it was the most affordable and accessible technique. Since it is not a strict approach, however, it is often useful to detect anomalies. In particular, observation of crystalline materials through optical microscopy can allow to differentiate between two crystal *habits* (their characteristic external shape), because this shape is governed by its molecular packing and intermolecular interactions (internal structure). Notwithstanding that more than a century has passed, it is still a routinely used technique, even if optical microscopy is being superseded by Scanning Electron Microscopy (SEM), which allows more accurate surface topology and morphology analysis. The closely related Transmission Electron Microscopy (TEM) was not appropriate for this kind of materials even given its uniqueness. It could collect structural and dynamic data from single crystals in a bulk powder and therefore, have remarkable benefits compared to any other. Unfortunately, the high energy applied to the samples caused strong damages precluding their characterization. Over years, researchers intended to reduce the applied voltage, seeking for this technique to be applicable by minimizing sample damage and improving cameras and detector technologies. This was especially aimed to the study of metal organic frameworks (MOFs), one of the most emerging topics with fundamental need to understand structure-properties relationship. Hence, breakthrough developments

#### *Polymorphism and Supramolecular Isomerism: The Impasse of Coordination Polymers DOI: http://dx.doi.org/10.5772/intechopen.96930*

in characterization techniques as cryogenic-TEM (cryo-TEM) [69] and High-Resolution TEM (HR-TEM) [70] paved the way to structural features at the nanometric scale as well as recent improvements for *in situ* measurements *inter alia* hot stage TEM, liquid cell TEM (LCTEM) [71] or environmental TEM (ETEM) [72] enabled to observe the dynamics of these systems. Advanced 3-dimensional electronic techniques as automated electron diffraction tomography (ADT) [73] and Rotation Electron Diffraction (RED) [74] were able to gather sufficient data for *ab initio* structure elucidation and thus succeeded where conventional diffraction techniques failed [75].

Despite all these advances, the most valuable technique has been and remains, single-crystal X-ray diffraction (SC-XRD). Only neutron diffraction is tantamount, being capable to collect specific and accurate data of atomic positions, bond distances, and angles [76]. Thus, serving as a complementary technique to SC-XRD. However, one must consider the possibility of temperature driven single-crystal to single-crystal transformations since a growing number of examples have been reported in the literature. Careful inspection of temperature effects on the sample is to be required. The generally used condition in SC-XRD is about 100 K which can undergo the phase transformation. If such events are not assured, one could fail at drawing conclusions of property changes from structural differences.

Although SC-XRD provides complete information about atom positions and structural packing, the growth of suitable crystals for structure determination is sometimes a laborious and very time-consuming task or even not attainable. Often, but nowadays less and less, it is not thought to be part of the endeavors of a chemist. That is why structural studies goes hand in hand with Powder X-Ray diffraction (PXRD), which is in many cases more available and can reflect any structural difference between SC-XRD and the bulk powder. But one must not forget that after ensuring no phase transformation, SC-XRD and neutron diffraction are the unique unambiguous techniques while the rest requires to be combined to successfully identify *polymorphism*. Recent advances in diffraction methodologies have enabled to improve PXRD characterization. For instance, variable temperature-PXRD and variable temperature-SC-XRD not only ease to determine differences in crystalline materials but also allow to trace phase transformations being subject to temperature changes.

Solid-state spectroscopic techniques are also a complementary tool during the identification of structural differences. Sometimes these changes are not evident but, in many cases, subtle structure modifications are reflected in the spectra. The most marked differences observable by Fourier Transformation Infrared Spectroscopy-Attenuated Total Reflectance (FTIR-ATR) [77] or Raman spectroscopies [78] usually appears in the fingerprint region since it is unique for a substance. In the case of polar molecules, transitions associated with rotation can be measured in absorption or emission by microwave or far infrared spectroscopies [79]. Also solid-state Nuclear Magnetic Resonance (SS-NMR) [80] as well as solid-state Ultraviolet–Visible absorption (SS-UV–Vis) [81] and fluorescence [82] have proven to be fruitful techniques to identify polymorphism and phase transformations. The recording of SS-NMR data can be improved by using Schaefer and Stejskal [83] experiments, in which high power heteronuclear decoupling, cross polarization (CP) and magic-angle spinning (MAS) are combined. Careful attention should be paid during MAS since the required high spinning rates generate mechanical stress and local heating, thus favoring conditions for transformations. *Isotopomeric polymorphs* [84] have also been identified, albeit in a lesser extent.

Solid-state Electron spin resonance (ESR) also known as Electron Paramagnetic Resonance (EPR) can be used only for materials containing paramagnetic metal

ions or structures in which those metal ions have been embedded. Copper(II) but also cobalt(II) are the archetypal metals for this technique and there already exist examples incorporating Cu(II) into the structures of templated materials [85]. More sophisticated variations include variable-temperature magnetic-susceptibility and variable-temperature solid-state EPR measurements. An increasingly common strategy combines them in the study of single-ion magnets (SIMs), a type of single-molecule magnets (SMMs). This EPR analysis is not easily available since it is preferably implemented with a synchrotron radiation source [86]. The magnetic evaluation of SIMs is performed in solid state so the structural differences between polymorphic forms promoted by conformational changes could lead to a dramatic alteration of the magnetic properties [87]. This effect is marked in Clathrochelates, a special class of structurally rigid cage metal complexes [88].

Last but not least, thermoanalytical techniques *inter alia* hot stage microscopy (also known as thermal microscopy), Thermogravimetric analysis (TGA), Differential Thermal Analysis (DTA) and Differential Scanning Calorimetry (DSC), are widely used to characterize both polymorphism as well as phase transformation phenomena. They are usually combined to maximize the efficiency of the data collection as TG-DTA or DSC-TGA, among others.

During hot stage microscopy, the sample is subjected to heating and cooling processes under polarized light. It provides *m.p.* data as well as, if it occurs, the reversible or irreversible character of the transition. TGA method is used to determine the thermal stability of the products and as previously mentioned, it is commonly combined with DTA. By the use of a thermobalance, it is capable to measure weight losses during temperature changes. It is especially useful to determine desolvation temperatures and thermal stability ranges but it is less accurate to quantify these transitions. The most appropriate technique to track phase transformations with quantitative data is DSC.

DSC is routinely used to measure the difference in the amount of heat required to increase the temperature of the sample respect to a reference. It is divided into power compensation DSC and heat-flux DSC methods. The quantification of the ∆*HtB A* , <sup>↔</sup> enables to identify its exo- or endothermic character, as well as the determination of reversible or not transitions provides essential data about the *enantiotropic* or *monotropic* behavior. DSC has not been deeply exploited yet for metal–organic materials but this practice is inevitably set to change. In particular, it is increasingly used in the study of breathing metal–organic frameworks (MOFs) [89] or solid-state phase transformations in Zeolitic imidazolate frameworks (ZIFs) [90].

Evidence of *polymorphism* can also be confirmed by nanoindentation or by optical properties as refractive index (*n*) or the identification of an interference figure caused by birefringence, which is the presence of different *n* and mainly depends on crystallographic orientations [91]. Once *polymorphism* has been identified and characterized, the proper conditions to isolate or to only reach one polymorphic form are to be established, avoiding the presence of mixtures and undesired products.

#### **4.2 Screening and isolation of polymorphic forms**

There are significant factors determining the formation of polymorphs *inter alia* molecular structure, chemical composition, energetic differences and experimental conditions (solvent, additives, pH, temperature and pressure). What should be clear is that the different polymorphic forms of a given structure can be selectively reach either by crystallization from the melt or solution, or by solid-state transformation. Crystallization approach has been the most widely studied heretofore but awareness of hitherto ignored solid-state transformations has led to value their tantamount importance. The solution-mediated approach is based on the proper

#### *Polymorphism and Supramolecular Isomerism: The Impasse of Coordination Polymers DOI: http://dx.doi.org/10.5772/intechopen.96930*

adjustment of the crystallization process and involves much more control of the polymorphs forming conditions. Instead, the advances in solid-state characterization techniques have triggered a significant increase of polymorphism studies allowing traceability of such conversions. This is especially the case of *coordination polymers* and MOFs, optimal materials for polymorphism study because of their flexibility and capability to accommodate structural modifications without the breaking of bonds.

The first step in polymorphs screening is to determine the phase space of a substance and the boundaries of stability for the different forms as well as identifying, if it is the case, interconversion. Defining the most stable phase is recommended since, unless modulating external factors dictate otherwise, that form would be the result. The occurrence of polymorphs and their transformations are confined to what is known as *occurrence domains* that encompass all the conditions in which the targeted crystal forms originate. Early studies carried out by Sato [92] on stearic acid delved deeply into the dependence of temperature and supersaturation on solvent polarity. Is in those regions with *domain* overlap where polymorphic transformations can occur, bearing in mind that the *domain* is not unique for one crystallographic form.

The many attempts to control the formation of a desired form have supplied us of a vast number of methods to selectively achieve it through crystallization or solid-state phase transformation. Most of the old and recent methods have been compiled in **Figure 4**. Further details about fundamental crystallization methods are found in Hulliger's review [93].

Over all of the difficulties of achieving isolated polymorphs, to identify the conditions to reach isolated forms is an essential task. When dealing with a polymorphic mixture scenario, the initial way of facing it, is the use of common crystallization methods as those mentioned before. However, crystallization of less stable forms is often intricated and therefore, it requires the design of more robust strategies *inter alia* high-pressure crystallization, spray-drying, crystallization from a melt or crystallization from a quenched amorphous phase. They give sometimes

#### **Figure 4.**

*Classification of the different methods to achieve polymorphic forms by crystallization or transformation.*

satisfactory results, but their major drawback is the lack of control in the formation of a single product. Hence, the use of additives and substrates was implemented as template though a limited triumph, considering that only thermodynamic aspects are contemplated and kinetic factors have a determinant role in nucleation. Subsequent methods as application of external fields, surface templating, selective nucleation by supersaturation control and nucleation temperature or seeding experiments emerged, but there is still a need for their improvement.

It is nevertheless important to note again that MOF materials are themselves appropriate candidates for filing structural modifications, since the predefined preferences of the organic linkers combined with those of the metal ions result in a restricted range of potential structures. This is strongly reflected in the common formation of isostructural products although they combine different linkers and metal ions. Such a controllable way of structure design is therefore adequate to identify new strategies for the isolation of different crystalline phases. Currently, throughout all the advances in MOFs design, *polymorphism* and *isomerism* awareness has driven the seeking of selective crystalline phase formation methods. For instance, in the case of mixed-metal MOFs, in which the addition of more than one metal ion disrupts the predefined structural formation, the selective phase formation has been achieved by the incorporation of guiding organic linkers or even metal ions to template the structural assembly. There was already consciousness of *polymorphism* and *isomorphism* in chromium(III) terephthalate MOFs [94], but


#### **Figure 5.**

*Properties likely to be altered by polymorphic modifications.*

the strategies to reach them were lacking. In 2018, Bureekaew [95] controlled the formation of this family of MOFs by using iron(III) metal-cationic competition, which served as *modulator* during crystallization. Likewise, Užarevic [85] demonstrated a rapid and selective way of controlling *polymorphism* in this family of MOFs by a mechanochemical approach using additives.
