Biochemical sensing with macrocyclic receptors

Abstract

Preventive healthcare asks for the development of cheap, precise and non-invasive sensor devices for the early detection of diseases and continuous population screening. The actual techniques used for diagnosis, e.g. MRI and PET, or for biochemical marker sensing, e.g. immunoassays, are not suitable for continuous monitoring since they are expensive and prone to false positive responses. Synthetic supramolecular receptors offer new opportunities for the creation of specific, selective and cheap sensor devices for biological sensing of specific target molecules in complex mixtures of organic substances. The fundamental challenges faced in developing such devices are the precise transfer of the molecular recognition events at the solid-liquid interface and its transduction into a readable signal. In this review we present the progress made so far in turning synthetic macrocyclic hosts, namely cyclodextrins, calixarenes, cucurbiturils and cavitands, into effective biochemical sensors and the strategies utilized to solve the above mentioned issues. The performances of the developed sensing devices based on these receptors in detecting specific biological molecules, drugs and proteins are critically discussed.

Carbon dots-inspired fluorescent cyclodextrins: competitive supramolecular “off–on” (bio)sensors

“…Chromophore-appended cyclodextrins (CDs) are spectroscopically active colourful systems engineered to exploit synergistically the supramolecular hosting capabilities of these glucosebased macrocycles with the optical properties of the affixed chromophores. 1,2 These dual conjugates are valuable photochemical molecular devices of paramount importance that have found increasing applications in many different areas with a heavy emphasis on imaging, drug delivery, and sensing. Among chromophores, fluorophores provide high sensitivity in analytical applications and a low detection limit in optical imaging methods.…”

Carboxylato-pillar[6]arene-based fluorescent indicator displacement assays for the recognition of monoamine neurotransmitters

“…[1][2][3] Articial receptor molecules operating through host-guest interactions capable of selective molecular recognition can be applied in supramolecular analytical systems to detect and quantify the analytes of interest. [4][5][6] Macrocycles, due to their inherent structural nature are ideal hosts for various biomolecules, however, attaching a signaling group to the water soluble derivatives is highly challenging. 7 This can be overcome by using uorescent indicator displacement (FID) assays, exploiting the competitive binding of a uorescent indicator to the macrocycle.…”

“…[21][22][23][24][25] In particular, water soluble pillararenes are prosperous hosts for various guests of biological importance. [26][27][28] Carboxylato-pillar [5]arene forms complexes with viologens (paraquat), 29,30 various amines and basic amino acids 31 that can be exploited to compile FID assays for these analytes. [32][33][34] Cationic, ammonium-containing pillar [5] arene was used as receptor in a FID sensor for various phenols.…”

“…[26][27][28] Carboxylato-pillar [5]arene forms complexes with viologens (paraquat), 29,30 various amines and basic amino acids 31 that can be exploited to compile FID assays for these analytes. [32][33][34] Cationic, ammonium-containing pillar [5] arene was used as receptor in a FID sensor for various phenols. 35 Amongst the higher homologues, carboxylato-pillar [6]arene can also recognise paraquat, 36 furthermore, ammonium-pillar [6] arene forms an exceptionally strong and selective complex with ATP 37 that can be used in nucleotide recognition.…”

Fluorinated Tetraphosphonate Cavitands

“…In view of their applications in biosensing [ 21 ], we selected the tetraphosphonate cavitands (Tiiii) [ 13 ] as the most valuable receptors for the insertion of fluorine probes. Herein, we report two synthetic protocols for the introduction of fluorine atoms into diester phosphonates [ 22 , 23 ] bridged cavitand scaffolds at the lower and upper rim, respectively ( Chart 1 ) and the response of the fluorine probes toward the complexation of sarcosine methyl ester hydrochloride, as a proxy of sarcosine.…”