Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors

abstract

A novel strategy for the recognition of anions in water using charge-neutral a-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, wealdy hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent a-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple sigma-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known a-hole receptors, including cationic systems (beta(2) up to 1.68 X 10(11) M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.

keywords

SOLID-STATE; AQUEOUS-SOLUTION; CHIRAL HALOGEN; FLUORIDE; BINDING; MOLECULES; INCLUSION; PEPTIDES; ROTAXANE; AFFINITY

subject category

Chemistry

authors

Borissov, A; Marques, I; Lim, JYC; Felix, V; Smith, MD; Beer, PD

Groups

G6 - Virtual Materials and Artificial Intelligence

Projects

Anion transmembrane transport promoted by drug-like molecules: building a library of anion carriers inspired in Ataluren (PTC124) (PTDC/QEQ-SUP/4283/2014)

CICECO - Aveiro Institute of Materials (UID/CTM/50011/2013)

acknowledgements

A.B. is grateful to the EPSRC Centre for Doctoral Training in Synthesis for Biology and Medicine (EP/L015838/1) for a studentship, generously supported by AstraZeneca, Diamond Light Source, Defence Science and Technology Laboratory, Evotec, GlaxoSmithKline, Janssen, Novartis, Pfizer, Syngenta, Takeda, UCB, and Vertex. J.Y.C.L. thanks the Agency for Science, Technology and Research (A*STAR), Singapore, for postgraduate funding. V.F. acknowledges support from project PTDC/QEQ-SUP/4283/2014 (POCI-01-0145-FEDER-016895) and CICECO - Aveiro Institute of Materials (UID/CTM/50011/2013), financed by National Funds through the FCT/MEC and cofinanced by QREN-FEDER through COMPETE under the PT2020 Partnership Agreement. I.M. is grateful for a postdoctoral grant (BPD/UI98/6065/2018) under project pAGE (reference Centro-01-0145-FEDER-000003).