Drew A. Fowler

Controlling the Self‐Assembly of Metal‐Seamed Organic Nanocapsules

The advent of modern molecular characterization techniques in the mid 20th century brought about a renaissance in our understanding of life s many processes. Notably, the structural determination of large biomolecules through the development of techniques such as NMR spectroscopy and X-ray diffraction (XRD) has given scientists valuable insight into the inner workings of cells. Many of these molecules are highly symmetrical, multicomponent entities, though determining the processes by which they assemble has been a difficult task. The biosynthesis of DNA, for example, came much later than its structural characterization by Watson and Crick. It is exactly this knowledge, however, that allows one to control the system. Supramolecular chemists have likewise endeavored to control the self-assembly processes in multicomponent entities. Although simpler than many biomolecules, the size and complexity of the macromolecules that embody this field largely preclude the use of standard mechanistic analyses that are applicable to smaller compounds. Our work has focused on metal-seamed pyrogallol[4]arene (PgC) nanocapsules. Forming rapidly through selfassembly, these large entities are composed of 2 or 6 macrocyclic units that act as chelates through their upper rims for 8, 12, or 24 metal ions (Figure 1). It is important to note that the 6-macrocycle, 24-metal ion hexameric nanocapsule results from the remarkable self-assembly of 30 entities. The dimeric or hexameric capsules are highly sym-

Ferrocene Species Included within a Pyrogallol[4]arene Tube

Research in host–guest complexes with ferrocene as a guest continues to attract attention. Macrocyclic hosts spanning from curcubiturils and cyclodextrins to resorcinarenes have been used to both encapsulate ferrocene and use as a component in nanometric frameworks. C-alkylpyrogallol[4]arenes (PgCs) are bowl-shaped compounds that are commonly used as building blocks in the construction of larger entities, such as capsules and nanotubes. Our work with C-methyl and C-heptylpyrogallol[4]arene has likewise shown that these compounds can function as hosts for ferrocene. The host–guest complex thus formed is a dimeric capsule with the enclosed and highly ordered ferrocene located between two PgC hemispheres. In addition to such capsular motifs, the conical shape of the calixarenes, resorcinarenes, and pyrogallolarenes can likewise lead to the formation of tubular solid-state structures. These often incorporate large nonsolvent molecules as part of the tubular framework. An excellent example of a PgC-based tubular framework that accommodates large nonsolvent molecules is the host–guest complex of Chexylpyrogallol[4]arene (PgC6) with pyrene. [9] In this complex, tetramers of PgC6 associate with one another through hydrogen bonding, whereas the pyrene molecules intercalate between the C-hexyl pendant arms of the PgC. This leads to two distinct regions within the structure: a hydrophilic tube that encloses guest solvents along with a hydrophilic tube that accommodates the pyrene. Herein, we describe a second host–guest complex of C-methylpyrogallol[4]arene (PgC1) and ferrocene that conforms to a tubular structural motif. In contrast to the capsular motif, a tubular hydrophobic cavity, rather than a capsular cage, is responsible for incarceration of the guest, whereas the hydroxyls of the PgC1 complexes along with polar solvent molecules form the long-range hydrogen-bonding superstructure. Slow changes in concentration of a PgC1 and ferrocene solution caused by evaporation led to the crystallization of this unique architecture. Methanolic solutions containing various ratios of PgC1 to ferrocene (with the concentration of ferrocene set at 10 3 molL ) were allowed to evaporate until crystallization was evident. At a 1:1 PgC1/ferrocene ratio, crystals of the previously reported dimeric product were the sole product. However, at ferrocene ratios of 6:1 or higher, two different crystal habits formed were found, with green needle-like crystals accompanying the dark blue prisms of the ferrocene dimer. X-ray diffraction analysis of the single crystal showed the dark green needles to be a novel tubular motif 1 featuring ferrocene “beads” in a hydrophobic cylinder of repeating trimers of PgC1. The tubular structure 1 (Figure 1) displays a complicated hydrogen-bonding arrangement of PgC1 complexes. Each tube consists of alternating units of 3 PgC1 complexes rotated by 608 relative to one another along the crystallographic C axis and a single ferrocene guest. The overall structure thus closely resembles a family of resorcinarene-based nanotubes described by Rissannen et al. However, in contrast to both the resorcinarene tubes and our previously reported

Cocrystallization of C-butyl pyrogallol[4]arene and C-propan-3-ol pyrogallol[4]arene with gabapentin

The single crystal X-ray diffraction structures for three cocrystals of C-butyl pyrogallol[4]arene and C-propan-3-ol pyrogallol[4]arene with the pharmaceutical gabapentin are described. The variation of solvent conditions and functionalities of the pyrogallol[4]arene tails demonstrates how these calixarene-like molecules can be used in the design of cocrystals with target molecules.

Zinc-seamed pyrogallol[4]arene dimers as structural components in a two-dimensional MOF

The synthesis of a two-dimensional (2D) metal–organic framework (MOF) is described wherein Zn-seamed pyrogallol[4]arene (PgCx) nanocapsules are utilized as supramolecular building blocks with 4,4′-bipyridine (bpy) linkers. The choice of linker and of crystallization solvent (DMSO) was guided by electronic structure calculations on the zinc model complexes Zn(C2H3O2)2L, which showed that bpy and DMSO have similar Zn–L binding strengths and that there is little drop-off in binding strength when bpy is bound to a second Zn(C2H3O2)2 moiety. The MOF features unusual coordination geometries at the zinc centres along the nanocapsular periphery when compared to previous examples of zinc-seamed nanocapsules. The change in coordination geometry leads to a compulsory change in the internal volume of the nanocapsule as well as the behaviour of the encapsulated guest molecule. There are also several well defined voids and channels within the structure.

Illuminating host–guest cocrystallization between pyrogallol[4]arenes and the ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate

The host–guest complexes of seven unique cocrystals containing pyrogallol[4]arenes and the ionic liquid 1-ethyl-3-methylimidazolium ethylsulfate are fully described. The investigation of these cocrystals is directed at expanding the control of the solid-state structures of these unique host–guest assemblies. The effects of varying conditions such as solvent choice and aliphatic tail length appended on the host macrocycle are explored and shed new light on the resultant supramolecular structures.

Spectroscopic investigations of pyrene butanol encapsulated in C-hexylpyrogallol[4]arene nanocapsules

Pyrogallol[4]arenes self-assemble to form stable hydrogen-bonded nanocapsules that have many unique properties making them potentially suitable for diverse applications, such as molecular transporters and nanoreactors. However, little is known about the host–guest behaviour of these materials. Utilizing nanoenvironment-dependent properties of the fluorescent reporter molecule, pyrene butanol (PBOH), the encapsulating abilities of the hexameric C-hexylpyrogallol[4]arene (PgC6) nanocages are further explored. Solution-state, spectroscopic and spectrofluorometric investigations and solid-state, single-crystal X-ray diffraction studies are in agreement and indicate an ordered inner phase. Up to two PBOH guest molecules are sequestered within the nanocapsule along with encapsulation solvent. The nature of the PBOH–PgC6 complex is found to change with time, as indicated by fluorophore leaching. These research findings provide additional insight into the encapsulation capabilities of PgCn nanocapsules.

Cocrystallization of pyrogallol[4]arenes with 1-(2-pyridylazo)-2-naphthol

Cocrystallizations of pyrogallol[4]arenes and 1-(2-pyridylazo)-2-naphthol (PAN) are investigated herein in order to determine the effect of aliphatic tail-length and solvent on crystal packing, probe orientation, and pyrogallol[4]arene bowl-shape. It is seen that solvent affects the final ratio of PAN to pyrogallol[4]arene, while aliphatic tail-length influences the crystal packing, C–H⋯π interactions, and overall hydrogen bonding. With an aliphatic tail-length of one carbon atom, there is an atypical bilayer structure. As the aliphatic tail-length increases, the resulting cocrystals have the characteristic bilayer structure as well as an increased number of C–H⋯π interactions and decreased hydrogen bonding with the PAN molecules.

Establishing trends based on solvent system changes in cocrystals containing pyrogallol[4]arenes and fluorescent probes rhodamine B and pyronin Y

Cocrystal systems containing pyrogallol[4]arene molecules of various aliphatic tail lengths, the fluorescent probe rhodamine B, and a variety of solvents are examined and discussed. Additionally, two pyronin Y cocrystals of C-methylpyrogallol[4]arene in methanol and C-ethylpyrogallol[4]arene in ethanol are crystallized and analyzed. For both the pyronin Y and rhodamine B cocrystals, solvent and aliphatic chain length have an effect on the packing, bowl shape of the pyrogallol[4]arene, probe complexation, and hydrogen bonding schemes. With pyronin Y cocrystals of C-methylpyrogallol[4]arene form a tube-like structure, with pyronin Y molecules in the centre of the tube while cocrystals of C-ethylpryogallol[4]arene form a bilayer-type structure.

Conversion of Pregabalin to 4-Isobutylpyrrolidone-2

Solid-state studies of C-butyl-resorcin[4]arene with pregabalin (Lyrica, Nervalin) in nitrobenzene yielded a cocrystal of C-butyl-resorcin[4]arene with 4-isobutylpyrrolidone-2. A combined experimental and quantum chemical investigation was implemented to further our understanding of the factors affecting the conversion process.

Erratum to “Conversion of Pregabalin to 4-Isobutylpyrrolidone-2”

Erratum to “Conversion of Pregabalin to 4-Isobutylpyrrolidone-2” Amanda M. Drachnik, Harshita Kumari, Collin M. Mayhan, Drew A. Fowler, Wei G. Wycoff, Charles L. Barnes, John E. Adams, Carol A. Deakyne, Jerry L. Atwood [J Pharm Sci 2017;106(10):3095-3102] The authors wish to include 3 corresponding authors: Correspondence to: Jerry L. Atwood (Telephone: 573-882-9606); Carol A. Deakyne (Telephone: 573-882-1347); Harshita Kumari (Telephone: 513-558-1872). E-mail addresses: AtwoodJ@missouri.edu (J. Atwood), DeakyneC@missouri.edu (C. Deakyne), kumariha@ucmail.uc.edu (H. Kumari).