Christopher Ceccarelli

Supramolecular recognition: On the kinetic lability of thermodynamically stable host–guest association complexes

A molecular receptor consisting of a spacer bearing two cofacially disposed terpyridyl–palladium–ligand (terpy-Pd-L) units rigidly separated by about 7 Å has been investigated for molecular recognition of planar aromatic molecules. It is found that although the receptor forms stable 1:2 host–guest association complexes with 9-methylanthracene (9-MA), the guest undergoes very rapid site exchange within the receptor and with external free 9-MA. A crystal structure of the 2:1 adduct shows one 9-MA in the molecular cleft defined by the two terpy-Pd-L units and the other resides on an outside face of one terpy-Pd-L unit. To establish the site residency time of the guests, a number of tethered molecules were prepared. These involve an anthracene molecule tethered to a pyridine ligand bound to the palladium atoms to form intramolecular host–guest adducts. Rotating-frame Overhauser effects were used to infer the site residency of the anthracene guests in the receptor. Variable-temperature 1H NMR spectroscopy of the intramolecular host–guest complexes has revealed that the site residency time of the anthracene guests is 1.6 × 10−5 sec at 20°C and 1.3 sec at −90°C in acetone solution. Whereas the guests are thermodynamically stable, they are kinetically very labile. A crystal structure of one of the tethered host–guest adducts reveals the expected structure which is the same as that determined in solution by 1H rotating-frame Overhauser enhancement spectroscopy experiments.

Structures of a labile copper redox couple: sterically constrained copper(II) and copper(I) complexes formed with a simple cyclic pentathia ether, 1,4,7,10,13-pentathiacyclopentadecane

Determination par diffraction RX des structures cristallines des complexes Cu II ([15]ane S 5 ) (ClO 4 ) 2 et Cu I ([15]ane S 5 ) (ClO 4 ). Coordination pyramidale a base carree autour des atomes Cu(II) et tetraedrique deformee autour des atomes Cu(I)

The crystal structure of calcium‐ and integrin‐binding protein 1: Insights into redox regulated functions

Calcium‐ and integrin‐binding protein 1 (CIB1) is involved in the process of platelet aggregation by binding the cytoplasmic tail of the αIIb subunit of the platelet‐specific integrin αIibβ3. Although poorly understood, it is widely believed that CIB1 acts as a global signaling regulator because it is expressed in many tissues that do not express integrin αIibβ3. We report the structure of human CIB1 to a resolution of 2.3 Å, crystallized as a dimer. The dimer interface includes an extensive hydrophobic patch in a crystal form with 80% solvent content. Although the dimer form of CIB1 may not be physiologically relevant, this intersub‐unit surface is likely to be linked to αIIb binding and to the binding of other signaling partner proteins. The C‐terminal domain of CIB1 is structurally similar to other EF‐hand proteins such as calmodulin and calcineurin B. Despite structural homology to the C‐terminal domain, the N‐terminal domain of CIB1 lacks calcium‐binding sites. The structure of CIB1 revealed a complex with a molecule of glutathione in the reduced state bond to the N‐terminal domain of one of the two subunits poised to interact with the free thiol of C35. Glutathione bound in this fashion suggests CIB1 may be redox regulated. Next to the bound GSH, the orientation of residues C35, H31, and S48 is suggestive of a cysteine‐type protein phosphatase active site. The potential enzymatic activity of CIB1 is discussed and suggests a mechanism by which it regulates a wide variety of proteins in cells in addition to platelets.