We report on the eligibility of tetraphosphonate resorcinarene cavitands for the molecular recognition of amino acids. We determined the crystal structure of 13 complexes of the tetraphosphonate cavitand Tiiii[H, CH3, CH3] with amino acids. 1H NMR and 31P NMR experiments and ITC analysis were performed to probe the binding between cavitand Tiiii[C3H7, CH3, C2H5] or the water-soluble counterpart Tiiii[C3H6Py+Cl-, CH3, C2H5] and a selection of representative amino acids. The reported studies and results allowed us (i) to highlight the noncovalent interactions involved in the binding event in each case; (ii) to investigate the ability of tetraphosphonate cavitand receptors to discriminate between the different amino acids; (iii) to calculate the Ka values of the different complexes formed and evaluate the thermodynamic parameters of the complexation process, dissecting the entropic and enthalpic contributions; and (iv) to determine the solvent influence on the complexation selectivity. By moving from methanol to water, the complexation changed from entropy driven to entropy opposed, leading to a drop of almost three orders in the magnitude of the Ka. However, this reduction in binding affinity is associated with a dramatic increase in selectivity, since in aqueous solutions only N-methylated amino acids are effectively recognized. The thermodynamic profile of the binding does not change in PBS solution. The pivotal role played by cation−π interactions is demonstrated by the linear correlation found between the log Ka in methanol solution and the depth of +N–CH3 cavity inclusion in the molecular structures. These findings are relevant for the potential use of phosphonate cavitands as synthetic receptors for the detection of epigenetic modifications of histones in physiological media.

The Origin of Selectivity in the Complexation of N-Methyl Amino Acids by Tetraphosphonate Cavitands

BRANCATELLI, GIOVANNA;GEREMIA, SILVANO;
2016-01-01

Abstract

We report on the eligibility of tetraphosphonate resorcinarene cavitands for the molecular recognition of amino acids. We determined the crystal structure of 13 complexes of the tetraphosphonate cavitand Tiiii[H, CH3, CH3] with amino acids. 1H NMR and 31P NMR experiments and ITC analysis were performed to probe the binding between cavitand Tiiii[C3H7, CH3, C2H5] or the water-soluble counterpart Tiiii[C3H6Py+Cl-, CH3, C2H5] and a selection of representative amino acids. The reported studies and results allowed us (i) to highlight the noncovalent interactions involved in the binding event in each case; (ii) to investigate the ability of tetraphosphonate cavitand receptors to discriminate between the different amino acids; (iii) to calculate the Ka values of the different complexes formed and evaluate the thermodynamic parameters of the complexation process, dissecting the entropic and enthalpic contributions; and (iv) to determine the solvent influence on the complexation selectivity. By moving from methanol to water, the complexation changed from entropy driven to entropy opposed, leading to a drop of almost three orders in the magnitude of the Ka. However, this reduction in binding affinity is associated with a dramatic increase in selectivity, since in aqueous solutions only N-methylated amino acids are effectively recognized. The thermodynamic profile of the binding does not change in PBS solution. The pivotal role played by cation−π interactions is demonstrated by the linear correlation found between the log Ka in methanol solution and the depth of +N–CH3 cavity inclusion in the molecular structures. These findings are relevant for the potential use of phosphonate cavitands as synthetic receptors for the detection of epigenetic modifications of histones in physiological media.
File in questo prodotto:
File Dimensione Formato  
jacs%2E6b04372.pdf

Accesso chiuso

Tipologia: Documento in Versione Editoriale
Licenza: Digital Rights Management non definito
Dimensione 2.85 MB
Formato Adobe PDF
2.85 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
2889724_jacs.6b04372-PostPrint.pdf

accesso aperto

Descrizione: Post Print VQR3
Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 3.38 MB
Formato Adobe PDF
3.38 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/2889724
Citazioni
  • ???jsp.display-item.citation.pmc??? 17
  • Scopus 62
  • ???jsp.display-item.citation.isi??? 62
social impact