Filamins are essential, evolutionary conserved, modular, multi-domain, actin-binding proteins that organize the actin cytoskeleton and maintain extracellular matrix connections by anchoring actin filaments to transmembrane receptors. By crosslinking and anchoring actin filaments, filamins stabilize the plasma membrane, provide cellular cortical rigidity and contribute to the mechanical stability of the plasma membrane and the cell cortex. In addition to actin, filamins interact with over 90 other binding partners including intracellular signaling molecules, receptors, ion channels, transcriptions factors and cytoskeletal and adhesion proteins. Thus, filamins scaffold a wide range of signaling pathways and are implicated in the regulation of a diverse array of cellular functions including motility, maintenance of cell shape and differentiation. Here, we review emerging structural and functional evidence that filamins are mechanosensors and/or mechanotransducers, playing essential roles in helping cells to detect and respond to physical forces in their local environment.

The halogen‐bonding interaction is one of the rising stars in supramolecular chemistry. Although other weak interactions and their influence on the structure and chemistry of various molecules, complexes and materials have been investigated thoroughly, the field of halogen bonding is still quite unexplored and its impact on chemistry in general is yet to be fully revealed. In principle, every Y–X bond (Y = electron‐withdrawing atom or moiety, X = halogen atom) can act as a halogen‐bond donor when the halogen is polarized enough by Y. Perfluorohalocarbons are iconic halogen‐bond donor molecules in which Y is a perfluorinated aryl or alkyl moiety and X is either iodine or bromine. In this article, alternative halogen‐bond motifs such as X2···A and Ar–X···A [A = Lewis basic halogen‐bond‐accepting atom of a molecule or ion; Ar = neutral or charged (hetero)aromatic system] are reviewed. In addition, haloalkenes, haloalkynes, N‐haloamides and other non‐metallic halogen‐bond donors and their respective halogen‐bonded structures will also be described. Although purely organic halogen‐bonding motifs are very prominent, the role of metal complexes in halogen bonding is becoming increasingly evident as well, which is also reflected in this review. Finally, halogen bonding in solution is briefly highlighted. Contemporary research is proving that halogen bonding is more than a solid‐state phenomenon and is now a well‐recognized weak interaction in chemistry.

A new (-)N-X(+)(-)O-N(+) paradigm for halogen bonding is established by using an oxygen atom as an unusual halogen bond acceptor. The strategy yielded extremely strong halogen bonded complexes with very high association constants characterized in either CDCl3 or acetone-d6 solution by (1)H NMR titrations and in the solid-state by single crystal X-ray analysis. The obtained halogen bond interactions, RXB, in the solid-state are found to be in the order of strong hydrogen bonds, viz. RXB ≈ RHB.

A study of the strong N−X⋅⋅⋅−O−N+ (X=I, Br) halogen bonding interactions reports 2×27 donor×acceptor complexes of N‐halosaccharins and pyridine N‐oxides (PyNO). DFT calculations were used to investigate the X⋅⋅⋅O halogen bond (XB) interaction energies in 54 complexes. A simplified computationally fast electrostatic model was developed for predicting the X⋅⋅⋅O XBs. The XB interaction energies vary from −47.5 to −120.3 kJ mol−1; the strongest N−I⋅⋅⋅−O−N+ XBs approaching those of 3‐center‐4‐electron [N−I−N]+ halogen‐bonded systems (ca. 160 kJ mol−1). 1H NMR association constants (KXB) determined in CDCl3 and [D6]acetone vary from 2.0×100 to >108 m−1 and correlate well with the calculated donor×acceptor complexation enthalpies found between −38.4 and −77.5 kJ mol−1. In X‐ray crystal structures, the N‐iodosaccharin‐PyNO complexes manifest short interaction ratios (RXB) between 0.65–0.67 for the N−I⋅⋅⋅−O−N+ halogen bond.

A simple 18-crown-6-based bis-urea receptor R(1) was synthesized in three steps from a commercial starting material. The receptor's behavior toward anions, cations, and ion pairs was studied in solution with (1)H NMR, in solid state with single-crystal X-ray diffraction, and in gas phase with mass spectrometry. In 4:1 CDCl3/dimethyl sulfoxide solution the receptor's binding preference of halide anions is I(-) < Br(-) < Cl(-) following the trend of the hydrogen-bonding acceptor ability of the anions. The receptor shows a remarkable positive cooperativity toward halide anions Cl(-), Br(-), and I(-) when complexed with Na(+), K(+), or Rb(+). The solid-state binding modes of R(1) with alkali and ammonium halides or oxyanions were confirmed by the X-ray structures of R(1) with KF, KCl, KBr, KI, RbCl, NH4Cl, NH4Br, KAcO, K2CO3, and K2SO4. They clearly present two different binding modes, either as separated or contact ion pairs depending on the nature and size of the bound cation and anion. Complexation capability of R(1) in the gas phase was studied with competition experiments with electrospray ionization mass spectrometry showing preference of KCl complexation over NaCl, KBr, or KI supporting the results obtained in solution.

N-Alkyl ammonium resorcinarene salts (NARYs, Y=triflate, picrate, nitrate, trifluoroacetates and NARBr) as tetravalent receptors, are shown to have a strong affinity for chlorides. The high affinity for chlorides was confirmed from a multitude of exchange experiments in solution (NMR and UV/Vis), gas phase (mass spectrometry), and solid-state (X-ray crystallography). A new tetra-iodide resorcinarene salt (NARI) was isolated and fully characterized from exchange experiments in the solid-state. Competition experiments with a known monovalent bis-urea receptor (5) with strong affinity for chloride, reveals these receptors to have a much higher affinity for the first two chlorides, a similar affinity as 5 for the third chloride, and lower affinity for the fourth chloride. The receptors affinity toward chloride follows the trend K1 ≫K2 ≫K3 ≈5>K4, with Ka =5011 m(-1) for 5 in 9:1 CDCl3/[D6]DMSO.

Mono-, di-and trivalent pseudorotaxanes with tetralactam macrocycle hosts and axles containing diamide binding stations as the guests have been synthesised. Their threading behaviour was analyzed in detail by NMR experiments and isothermal titration calorimetry. An X-ray crystal structure of the monovalent pseudorotaxane confirms the binding motif. Double mutant cycle analysis provides the effective molarities and insight into the chelate cooperativity of multivalent binding. While the second binding event in a trivalent pseudorotaxane exhibits a slightly positive cooperativity, the third binding is nearly non-cooperative. Nevertheless, the enhanced binding affinities resulting from the multivalent interaction are the basis for a highly efficient synthesis of di-and trivalent rotaxanes through stoppering the axle termini by "click" chemistry. Evidence for the multiply threaded geometry comes from NMR spectroscopy as well as tandem mass-spectrometric fragmentation experiments of mass-selected rotaxane ions in the gas phase. Furthermore, the trivalent rotaxane can be controlled by external stimuli (chloride addition and removal) which lead to an elevator-type movement of the wheel along the axle.

A study of the strong N−X⋅⋅⋅−O−N+ (X=I, Br) halogen bonding interactions reports 2×27 donor×acceptor complexes of N‐halosaccharins and pyridine N‐oxides (PyNO). DFT calculations were used to investigate the X⋅⋅⋅O halogen bond (XB) interaction energies in 54 complexes. A simplified computationally fast electrostatic model was developed for predicting the X⋅⋅⋅O XBs. The XB interaction energies vary from −47.5 to −120.3 kJ mol−1; the strongest N−I⋅⋅⋅−O−N+ XBs approaching those of 3‐center‐4‐electron [N−I−N]+ halogen‐bonded systems (ca. 160 kJ mol−1). 1H NMR association constants (KXB) determined in CDCl3 and [D6]acetone vary from 2.0×100 to >108 m−1 and correlate well with the calculated donor×acceptor complexation enthalpies found between −38.4 and −77.5 kJ mol−1. In X‐ray crystal structures, the N‐iodosaccharin‐PyNO complexes manifest short interaction ratios (RXB) between 0.65–0.67 for the N−I⋅⋅⋅−O−N+ halogen bond.