Cucurbit[5]uril derivatives as oxygen carriers

Abstract

Cucurbituril derivatives as oxygen carriers Cucurbit[n]urils are rigid cage-molecules of pumpkin-like shape, made of nglycoluril units, able to bind mainly neutral molecules and cations. In this work, we investigate the binding of three cucurbit[5]uril derivatives with dioxygen O2 and show that one of them, namely per-hydroxylated cucurbit[5]uril, (OH)10CB[5], is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. As cucurbit[n]urils studied up to now reveal low toxicity, per-hydroxylated cucurbit[5]uril appears as a promising precursor to design a host able to transport O2 in a haemoglobin substitute solution.

Challenges and Opportunities of Functionalized Cucurbiturils for Biomedical Applications

“…• CB[5]-(OH) 10 has shown a great potential for oxygen transport which could open the way to a potent artificial hemoglobin. 60 It would now be interesting to check its toxicity in detail and investigate this behavior in vivo.…”

“…The modest size of the CB[5] cavity is suitable to include several gas molecules, such as N 2 , O 2 , Ar, NO, or CO 2 as documented for decamethyl-CB[5] ( CB­[5]-(Me) 10 ) in the solid state . Later, Huber and co-workers showed that per-hydroxylated-CB[5] ( CB­[5]-(OH) 10 , Figure ) could bind O 2 at 37 °C and in the presence of NaCl at a concentration relevant in blood (but not CB­[5]-(Me) 10 ) . Even if toxicology studies are required to confirm the relevance of CB­[5]-(OH) 10 to transport oxygen in biological media, these results are promising enough to envision its use as a substitute to hemoglobin.…”

“…The protocols now available, even if still far from perfect (yields for monofunctional compounds and purification methods can, and should, be improved), have enabled preparation of a myriad of CB derivatives having shown a plethora of interesting properties. More specifically: CB­[5]-(OH) 10 has shown a great potential for oxygen transport which could open the way to a potent artificial hemoglobin . It would now be interesting to check its toxicity in detail and investigate this behavior in vivo.…”

Supramolecular chemistry of substituted cucurbit[n]urils

“…Huber et al recently investigated the binding of three substituted Q [5]s with dioxygen O 2 . 141 The study revealed that the (HO) 10 Q [5] is able to significantly bind dioxygen gas at physiological temperature, even in the presence of sodium chloride at the concentration of injectable solution in blood. The study suggests the potential utility of (HO) 10 Q [5] as a precursor host to transport O 2 in a hemoglobin substitute solution.…”

The Cyclobutanocucurbit[5–8]uril Family: Electronegative Cavities in Contrast to Classical Cucurbituril while the Electropositive Outer Surface Acts as a Crystal Packing Driver

“…In solution, it was previously observed that equatorial substitution has an effect upon the binding affinities of various molecular guests, where affinities can increase or decrease relative to the same guest molecule [ 20 , 21 , 22 , 29 , 30 , 31 , 32 ]. In the case of partially substituted derivatives such as Me 4 Q[6] and Me 4 Q[8] ( Figure 1 , bottom), a distortion in the cavity can partly explain a change in the binding affinity, which is also dependent upon the guest’s shape [ 20 , 21 , 22 , 31 ], whereas, with full substitution, the Q cavities are spheroidal and effects upon binding affinities in solutions can best be explained by electronic changes, the degree of Q structure rigidity, and variations in diameters of the portals and cavities.…”