Carborane Guests for Cucurbit[7]uril Facilitate Strong Binding and On-Demand Removal

Abstract

High affinity guests have been reported for the macrocyclic host cucurbit[7]uril (CB[7]), enabling widespread applications, but preventing CB[7] materials from being returned to their guest-free state for reuse. Here we present polyhedral boron clusters (carboranes) as strongly-binding, yet easily removable, guests for CB[7]. Aided by a Pd-catalyzed coupling of an azide anion, we prepared boron-functionalized 9-amino and 9-ammonium modified ortho-carboranes that bind to CB[7] with a Ka=10 10 M-1. Upon treatment with base, the orthocarboranes readily undergo deboronation to yield anionic nido-carborane, a poor guest of CB[7], facilitating recovery of guest-free CB[7]. We showcase the utility of the modified ortho-carborane guest by recycling a CB[7]functionalized resin. With this report, we introduce stimuli-responsive decomplexation as an additional consideration in the design of high affinity host-guest complexes. Molecular recognition is ubiquitous within the natural world with the genetic code, enzymes, and immune systems all reliant on non-covalent interactions between biomolecules. 1,2 These phenomena have inspired chemists to develop host-guest complexes in hopes of achieving comparable degrees of specificity for applications in functional materials, 3 sensors, 4 biological assays, 5 and therapeutics. 6-9 Much of the early molecular recognition work involved crown ether, cyclophane, and cyclodextrin hosts that exhibit modest binding affinities (Ka<10 5 M-1). 10 More recently, there has been a focus on the development of high affinity (Ka>10 10 M-1) host-guest complexes that rival the binding affinities of Nature's best molecular recognition systems: antibody-antigens and (strept)avidin-biotin. 11 High binding affinity complexes

Expanding the Scope of Palladium-Catalyzed B – N Cross- Coupling Chemistry in Carboranes

“…Notably, compared with reported crystal structure of carboranyl azide with the azide group on the carbon vertex of o-carborane, 17 The asymmetric stretching frequency of the azide group in 1a (2124 cm -1 ) compares well with that reported for 2a (2121 cm -1 ). 14 Xie and co-workers previously reported a stretching frequency of 2149 cm -1 for the synthesized 3-N3-o-carborane. 12b This appreciable difference in azide stretches based on vertex-attachment stands in contrast to analogous aryl systems in which it has been noted that the electronic landscape of the aryl ring has little measurable effect on the azide IR stretching and bending frequencies.…”

“…12 In 2016, our group discovered B-bromocarboranes -previously assumed to be unreactive cross-coupling substrates -can act as competent electrophiles in Pd-catalyzed cross-coupling chemistry, leading to successful substitutions at various B-based vertices from the corresponding brominated carboranes. 13 Capitalizing on this discovery, we recently syn- thesized 9-azido-ortho-carborane from the corresponding brominated precursor; 14 notably, while this chemistry aligns with the apparent generality of other cross-coupling reactions involving B-bromocarborane electrophiles, 7 to our knowledge an analogous Pd-catalyzed cross-coupling strategy to synthesize aryl azides from aryl (pseudo)halide electrophiles has not been disclosed. Importantly, this product could ultimately be reduced to the free amine under acidic conditions, constituting the first synthesis of primary amine derivative at B(9) of o-carborane.…”

Access to cationic polyhedral carboranes via dynamic cage surgery with N-heterocyclic carbenes

“…On the contrary, o-2 and m-2 were unexpectedly converted into their corresponding hydrochlorides o-2a and m-2a, which is, to the best of our knowledge, the first example of a proton capture by a neutral borane cage leading to the formation of a cation without any changes in the functional groups. Such a reactivity is known for of amino, sulfido or phosphino based exoskeletal functional groups protonation or quaternization [30][31][32] . In this respect, there is only one example of the substitution of sulfide groups in bis-dialkylsulfidododecahydrodecaborane with hydrogen halogenides 45 .…”

“…At the same time, the number of the SEPs for monocationic clusters is likely to be different, n + 0.5 for closo up to n + 3.5 for hypho, but the cationic clusters are still elusive, except for closo-B 12 (3-methylbutyl) 12 + radical cation published very recently by Spokoyny 29 . There is a big number of cationic boranes, however, the positive charge is predominantly located on a functional group connected to the parent borane (Me 2 S 30 , phosphonium 31 and ammonium 32 ), not in the borane cage itself.…”

Quantitative Heterodimerization of Aromatic Peptides through Host-Enhanced Polar–π Interactions for On-Resin Recognition

“…Two series of tripeptides (GGX, GXG), containing aromatic amino acids either at the C termini or in the middle of the chain, were synthesized to investigate diversity of the second guest and its distance away from the positive charge, Chart S1. After elucidating the thermodynamics of the system, we applied this heterodimerization approach to achieve on-resin recognition and isolation [29] of aromatic peptides from a peptide mixture exhibiting high efficiency and selectivity, Figure 1c.…”