A molecular communication channel consisting of a single reversible chain of hydrogen bonds in a conformationally flexible oligomer

Abstract

Summary Communication of information through the global switching of conformation in synthetic molecules has hitherto entailed the inversion of chirality. Here, we report a class of oligomer through which information may be communicated through a global reversal of polarity. Ethylene-bridged oligoureas are constitutionally symmetrical, conformationally flexible molecules organized by a single chain of hydrogen bonds running the full length of the oligomer. NMR reveals that this hydrogen-bonded chain may undergo a coherent reversal of directionality. The directional uniformity of the hydrogen-bond chain allows it to act as a channel for the spatial communication of information on a molecular scale. A binding site at the terminus of an oligomer detects local information about changes in pH or anion concentration and transmits that information—in the form of a directionality switch in the hydrogen-bond chain—to a remote polarity-sensitive fluorophore. This propagation of polarity-encoded information provides a new mechanism for molecular communication.

Reversible Capture and Release of a Ligand Mediated by a Long-Range Relayed Polarity Switch in a Urea Oligomer

“…A 1:1 binding model gave binding constants of 1490 ± 82 M –1 (for 1 ) and 311 ± 21 M –1 (for 2 ), 28 showing that 1 binds the phosphine oxide almost 5 times more strongly than 2 . The BTMP urea is itself a powerful hydrogen bond donor, 20 but these results demonstrate that the even more strongly hydrogen-bond-donating thiourea in 1 can override the BTMP urea’s hydrogen-bonding preference.…”

“…Communication devices of this type are commonplace in biology, − and analogous spatial molecular communication has been achieved in synthetic molecules by induction of conformational changes at the terminus of an oligomeric structure. − Examples have involved communication of chirality through contiguous atropisomeric axes or the screw-sense preference of a helix or communication of polarity through a flexible chain of hydrogen bonds. , Without exception, such synthetic communication devices either exploit intra molecular interactions , or undergo irreversible change through chemical reaction, ,, precluding more general and reversible chemical function. To date, there is no artificial molecular communication device that allows continuous remote control of inter molecular interactions commonly seen in biology.…”

“…We chose as this terminal binding site an electron-deficient N,N′-disubstituted urea function (Ar = 3,5-bis­(trifluoro­methyl)­phenyl, abbreviated as “BTMP urea”) . To establish the ability of induced hydrogen bond polarity to govern the local conformation of the BTMP ureaand hence its availability for ligand bindingoligomers 1 and 2 were synthesized (Figure a) in which each polarity-controlling group (the thiourea hydrogen bond donor in 1 and the N , N ′-dimethylurea hydrogen bond acceptor in 2 ) is separated from the BTMP urea by a hydrogen-bonded chain of three trisubstituted ureas . We expected these molecules to maximize the stability of their hydrogen-bonded network by adopting hydrogen-bonding patterns of opposite directionality.…”

Dissecting Solvent Effects on Hydrogen Bonding

“…Several synthetic systems have repurposed biological H‐bonding motifs, but controlling and predicting the behavior of de novo H‐bonding systems in competitive solvents is more difficult. This situation has been highlighted in medicinal chemistry, [13–16] the construction of H‐bonding chains, [17–23] and sugar binding [24–28] in competitive solvents. Therefore, it remains desirable to quantify individual H‐bonds in competitive solvents to better understand their behavior.…”

Isotope Ratio Encoding of Sequence-Defined Oligomers

“…Furthermore, proteins engage in all kinds of recognition and chemical manipulations that constantly convey information through, for example, signaling cascades or allosteric transitions. The level of performance of biopolymers has quite understandably represented a huge source of inspiration for chemists to develop artificial systems capable of some sort of translation − or to transport the information associated with a chemical signal through concerted conformational changes. , …”