Incorporation of carboxylated pillar[5]arene and strontium(<scp>ii</scp>) into supramolecular coordination complexes of different nuclearities

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Here we describe the inclusion of the minor-groove binding drug pentamidine in its extended conformation into the macrocyclic cavity of water-soluble carboxylated pillar[5]arene. The artificial host−guest system is manifested as an ensemble of three crystalline forms differing in the pillar[5]arene−pentamidine interaction mode, solvation type, and even stoichiometry. The strong hydrogen bonds of various types of amidinium−carboxylate (between pentamidine and pillar[5]arene) and carboxylic− carboxylate (between adjacent pillar[5]arenes) are realized in all complexes, rigidifying the assembly. However, it seems that more subtle effects, such as local solvation/desolvation, a certain degree of flexibility of both the host and guest, and variable protonation/ deprotonation state of the pillar[5]arene substituents, play significant roles in the peculiar crystallization behavior of the system. The snapshots of three crystal structures highlighting various binding geometries and intermolecular interaction modes between the same host and guest present exciting opportunities in terms of more holistic models of the host−guest systems, shifting from focusing our attention on "visible interactions" in one crystal structure to the appreciation of many subtle effects playing a combined role in the host−guest chemistry.

Section: Resultsmentioning

confidence: 55%

Inclusion of Pentamidine in Carboxylated Pillar[5]arene: Late Sequential Crystallization and Diversity of Host–Guest Interactions

Butkiewicz

Kosiorek

Sashuk

et al. 2022

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“…17 In our further solid state structural studies CPA5 has shown its ability to complex viologen derivatives 18 and to form coordination polymers with alkali-earth cations. 19 Recently, we have demonstrated the rich host−guest chemistry of CPA5pentamidine crystal complexes highlighting the role of amidinium-carboxylate hydrogen bonding and cavity inclusion. 20 Despite the thriving interest in the aqueous complexation properties of larger pillar[n]arenes, 21,22 their solid state supramolecular chemistry has remained a mystery.…”

mentioning

confidence: 99%

“…Satisfying our scientific curiosity with a view to design and construct novel supramolecular structures, we managed to crystallize carboxylated pillar[5]arene ( CPA5 ) in the form of inclusion complexes with ethanol and the anesthetic drug tetracaine in 2015 . In our further solid state structural studies CPA5 has shown its ability to complex viologen derivatives and to form coordination polymers with alkali-earth cations . Recently, we have demonstrated the rich host–guest chemistry of CPA5 -pentamidine crystal complexes highlighting the role of amidinium-carboxylate hydrogen bonding and cavity inclusion …”

mentioning

confidence: 99%

Carboxylated Pillar[6]arene Emulates Pillar[5]arene in the Host–Guest Crystal Complexes and Shows Conformational Flexibility in the Solution/Gas Phase

Butkiewicz

Kosiorek

Sashuk

et al. 2022

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Despite the thriving interest in the aqueous complexation properties of carboxylated pillar [6]arene, its solid state supramolecular chemistry has remained a mystery. Here, overcoming challenging crystallogenesis, we report the first crystallographic authentication of carboxylated pillar [6]arene in the form of two host−guest inclusion complexes with methyl viologen and pentamidine.The key to the successful crystallization of carboxylated pillar[6]arene is the mixed ionization state of its 12 carboxylic substituents. The deprotonation of several but not all substituents enables intermolecular hydrogen bonding and, as a result, "gluing" and crystallization of pillar[6]arene complexes with the aid of carboxylic-carboxylate, carboxylic-carboxylic, and amidinium-carboxylate supramolecular synthons. Single crystal X-ray diffraction analysis revealed that upon guest inclusion pillar[6]arene adopts a quasi-pentagonal shape rather than the expected hexagonal shape. The squeezed quasi-pentagonal conformation of the six-membered macrocycle is stabilized by two intramolecular hydrogen bonds between pillar[6]arene substituents. Moreover, the distinctive deviation of the macrocycle from hexagonal shape stays operative in the solution/gas phase as concluded from ion mobility mass spectrometry (IM-MS) studies and theoretical calculations. These results provide the first insight into how to gain control over the conformation of flexible pillar[6]arene with a view of solid state design of more advanced supramolecular host−guest structures.

“…We managed for the first time to trap in the crystal state both pillar[5]arene and pillar[6]arene in the form of host–guest complexes. We have shown that carboxylated pillar[5]arene ( CPA5 ) forms inclusion and exclusion complexes with electron-deficient viologen guests and coordination complexes with metal cations . In the current study, we have chosen two biguanide cationic guests, alexidine ( ALEX ) and phenformin ( PFM ), as partner species to crystallize with CPA5 , as shown in Figure .…”

Section: Introductionmentioning

confidence: 99%

“…We have shown that carboxylated pillar [5]arene (CPA5) forms inclusion and exclusion complexes with electron-deficient viologen guests 16 and coordination complexes with metal cations. 17 In the current study, we have chosen two biguanide cationic guests, alexidine (ALEX) and phenformin (PFM), as partner species to crystallize with CPA5, as shown in Figure 1. Biguanides are important pharmaceutical molecules of the rich palette of activity; they have been used inter alia as antidiabetic, antiseptic, or antimalaria drugs.…”

Section: ■ Introductionmentioning

confidence: 99%

Carboxylated Pillar[5]arene Meets Medicinal Biguanides: Host–Guest Complexes with Alexidine and Phenformin in the Crystal and Solution/Gas Phase

Butkiewicz,

Kosiorek,

Sashuk

et al. 2023

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Here, we discuss crystal and solution/gas-phase complexes of carboxylated pillar [5]arene with two cationic guests, alexidine and phenformin, revealing host−guest and assembly curiosities, the role of hydrogen bonding, and cavity inclusion versus exo-mode binding. We show that the combination of carboxylated pillar[5]arene with bis(biguanidinium) guest alexidine results in the crystallization of open-type supramolecular architecture. This is also the first crystal structure of alexidine ever reported. The crystallization of pillar[5]arene with biguanidinium drug phenformin affects a rare solid-state complex comprising two cavity inclusion modes within the same crystal lattice. The winner in the competition between ethanol molecules and an organic cation (phenformin) for access to the cavity of pillar[5]arene is undecided, visualized as a "snapshot" of these two inclusion possibilities in one crystal structure. Our results demonstrate that carboxylated pillar[n]arenes can be a useful addition to the macrocyclic toolkit for the facilitation of the crystallization of bio(macro)molecules. Moreover, the IM-MS analysis of the precrystallization solutions of pillar[5]arene host and biguanide guests has shown the presence of structures and conformations closely related to those observed in the crystal forms. The most intriguing results obtained for a pillar[5]arene−alexidine complex imply a conformational evolution of the complex over 24 h. The IM-MS analysis complemented by theoretical calculations may be applied to predict and examine the crystallization process of host−guest systems, complementing crystallographic studies.