Regioselective long-range proton transfer in new rifamycin antibiotics: a process in which crown ethers act as stronger Brønsted bases than amines

Chemphyschem. 2015 Apr 7;16(5):938-42. doi: 10.1002/cphc.201402892. Epub 2015 Jan 29.

Abstract

Water-mediated proton transfer in six new derivatives of 3-formylrifamycin SV that contain crown, aza-crown, and benzo-crown ether rings were investigated by FTIR and NMR spectroscopy. (1)H-(1)H COSY couplings provide evidence for the formation of zwitterionic structures of the aza-crown and crown ether derivatives of rifamycin, in which a proton from one of the phenolic groups is transferred to tertiary and secondary nitrogen atoms. The increased intensity of the continuous absorption in the mid-infrared region together with the NMR data indicate proton transfer from the phenol group of the rifamycin core to the cavity of the benzo-crown ether ring. This proton transfer is achieved by formation of hydronium (H3O(+)) or Zundel ions (H5O2(+)), which form intermolecular hydrogen bonds with the oxygen atoms of the crown ether. DFT calculations are in agreement with the spectroscopic data and allow visualization of the structures of all new rifamycin derivatives, characterized by different intramolecular protonation sites.

Keywords: NMR spectroscopy; Zundel cation; density functional calculations; proton transfer; rifamycins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Anti-Bacterial Agents / chemistry*
  • Crown Ethers / chemistry*
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Protons
  • Rifamycins / chemistry*
  • Spectroscopy, Fourier Transform Infrared
  • Stereoisomerism

Substances

  • Amines
  • Anti-Bacterial Agents
  • Crown Ethers
  • Protons
  • Rifamycins
  • rifamycin SV