Ligation Motifs in Zinc-Bound Sulfonamide Drugs Assayed by IR Ion Spectroscopy

Molecules. 2022 May 14;27(10):3144. doi: 10.3390/molecules27103144.

Abstract

The sulfonamide-zinc ion interaction, performing a key role in various biological contexts, is the focus of the present study, with the aim of elucidating ligation motifs in zinc complexes of sulfa drugs, namely sulfadiazine (SDZ) and sulfathiazole (STZ), in a perturbation-free environment. To this end, an approach is exploited based on mass spectrometry coupled with infrared multiple photon dissociation (IRMPD) spectroscopy backed by quantum chemical calculations. IR spectra of Zn(H2O+SDZ-H)+ and Zn(H2O+STZ-H)+ ions are consistent with a three-coordinate zinc complex, where ZnOH+ binds to the uncharged sulfonamide via N(heterocycle) and O(sulfonyl) donor atoms. Alternative prototropic isomers Zn(OH2)(SDZ-H)+ and Zn(OH2)(STZ-H)+ lie 63 and 26 kJ mol-1 higher in free energy, respectively, relative to the ground state Zn(OH)(SDZ)+ and Zn(OH)(STZ)+ species and do not contribute to any significant extent in the sampled population.

Keywords: DFT calculations; FTICR mass spectrometry; IRMPD spectroscopy; metal complexes; structure determination; sulfadiazine; sulfathiazole; sulfonamide antibiotics; zinc coordination.

MeSH terms

  • Ions
  • Spectrophotometry, Infrared
  • Sulfanilamide
  • Sulfonamides*
  • Zinc* / chemistry

Substances

  • Ions
  • Sulfonamides
  • Sulfanilamide
  • Zinc

Grants and funding

This research was funded by Sapienza Università di Roma (grant number RM120172A92B25D8) and by the EU Horizon 2020 Programme (CALIPSOPlus and EU_FT-ICR_MS, under grant numbers 730872 and 731077, respectively).