Non-Covalent Interactions Behind the Anion Recognition: Bonding

Situation in Metalated Calixarene Hosts

Alexandre O. Ortolan1*, Ina Østrøm1, Giovanni F. Caramori1, Renato L. T. Parreira2,
Alvaro Muñoz-Castro3, F. Matthias Bickelhaupt4,5
1
Universidade Federal de Santa Catarina, Florianópolis, Brazil. 2 Universidade de Franca,
Franca, Brazil. 3 Universidad Autonoma de Chile, Santiago, Chile. 4 Vrije Universiteit
Amsterdam, Amsterdam, The Netherlands. 5 Radboud University, Nijmegen, The
Netherlands.

alexandre.osmar@posgrad.ufsc.br

Introduction

Non-covalent interactions (NCI) are the primary forces involved in the

recognition, transport, and regulation of many events in biological systems.1 Although
the critical role of anionic molecules is well known, the chemistry of anion receptors is
still a growing area.2 For instance, the anion–π interactions in a series of heterocalixarenes
hosts were recently addressed by us.3,4 In this connection, Atwood and co-workers5
reported the synthesis and characterization of a series of macrocyclic complexes based on
calix[4]-arene and its derivatives, water-soluble and air-stable, possessing an inner
hydrophobic cavity suitable to incorporate anionic species via noncovalent interactions.5,6
Their host capability was confirmed by X-ray crystallography in recognizing BF4-, SO42-,
and I-.6 Based on these host-guest complexes (Fig. 1A) we performed a comprehensive
electronic-structure analysis of the physical nature of the noncovalent interactions
involved in anion recognition in metalated calix[4]arene hosts at DFT-D level of theory.7

Computational Methodology

All calculations were performed at ZORA-BP86-D3(BJ)/TZ2P level of theory at

ADF 2016 software.7 The non-covalent interactions were investigated by employing
Kohn-Sham molecular orbital (KS-MO) theory in conjunction with a canonical energy
decomposition analysis (EDA).8 To give support to the KS-MO/EDA analysis, the
molecular electrostatic potential maps (MEPs), the Hirshfeld and NPA charge analysis,
and the ion-dipole contribution to the electrostatic energy term were also computed at the
same level of theory.7

Results and Discussion

Our results reveal that the anion–π interactions are strengthened and can be
efficiently tuned through the proper choice of the exo-coordinating metal fragment to the
host’s arene moieties. Furthermore, the guest’s steric fit in the host framework is a
selective and crucial criterion for the anion recognition. The fit of small anions occurs


with less geometrical deformation of the host cavity and thus less destabilizing
deformation strain upon accommodating the anion. Our quantitative analyses of the
bonding mechanism reveal the most stable host-guest situation occurs in ruthenium
complexed hosts, followed by technetium and molybdenum macrocyclic receptors (Fig.
1B). The coordinated metals provide a substantial electrostatic stabilization to anion
recognition, making the calixarene cavity a more electron deficient and turning it into a
stronger π-acid. The interaction is further reinforced by donor-acceptor interactions
between the guest’s HOMO and the empty π*-type orbitals in the calixarene bowl (Fig.
1C).

A B Cl-
C
Mo0 Br -

Tc+ I-
perspective
Ru2+

Host-guest systems metals BF4-

upper view lower view guests
guest host-guest host

Figure 1. Optimized host-guest structures (A), employed metals and anions guests (B), and orbital-
interaction diagram based on Kohn-Sham MO analysis (C).

Conclusions

Our results highlight the enormous anion-recognition capability of organometallic

calixarenes. We envisage that this will encourage attempts to rationally design and
synthesize highly selective hosts.

Acknowledgments
AOO and GFC thanks CNPq (grants 142339/2015-6 and 311963/2017-0), IØ and
RLTP thanks CAPES (grants 1732086 and 88881.068346/2014-01). RLTP thanks
FAPESP (grant 2011/07623-8). AMC thanks FONDECYT (grant 1180683). FMB thanks
NWO.
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