H.P. Dijkstra

Solid-state structural characterization of cutinase-ECE-pincer-metal hybrids

The first crystal structures of lipases that have been covalently modified through site-selective inhibition by different organometallic phosphonate-pincer-metal complexes are described. Two ECE-pincer-type d(8)-metal complexes, that is, platinum (1) or palladium (2) with phosphonate esters (ECE = [(EtO)-(O=)P(-O-C(6)H(4)-(NO(2))-4)(-C(3)H(6)-4-(C(6)H(2)-(CH(2)E)(2))](-); E = NMe(2) or SMe) were introduced prior to crystallization and have been shown to bind selectively to the Ser(120) residue in the active site of the lipase cutinase to give cut-1 (platinum) or cut-2 (palladium) hybrids. For all five presented crystal structures, the ECE-pincer-platinum or -palladium head group sticks out of the cutinase molecule and is exposed to the solvent. Depending on the nature of the ECE-pincer-metal head group, the ECE-pincer-platinum and -palladium guests occupy different pockets in the active site of cutinase, with concomitant different stereochemistries on the phosphorous atom for the cut-1 (S(P)) and cut-2 (R(P)) structures. When cut-1 was crystallized under halide-poor conditions, a novel metal-induced dimeric structure was formed between two cutinase-bound pincer-platinum head groups, which are interconnected through a single mu-Cl bridge. This halide-bridged metal dimer shows that coordination chemistry is possible with protein-modified pincer-metal complexes. Furthermore, we could use NCN-pincer-platinum complex 1 as site-selective tool for the phasing of raw protein diffraction data, which shows the potential use of pincer-platinum complex 1 as a heavy-atom derivative in protein crystallography.

Metathesis of olefin-substituted pyridines: the metalated NCN-pincer complex in a dual role as protecting group and scaffold.

Pincer-palladium(II) and -platinum(II) cat- ions, YCY-M (YCY (2,6-(YCH2)2C6H3) ;Y NMe2, SPh; M Pd II ,P t II ), bound to diolefin-substituted pyridines (3,5- or 2,6-substitution) were successfully synthesized, and subsequently used in olefin meta- thesis (RCM) as a model study for template-directed synthesis of macrocycles. Especially a 3,5-disubstitut- ed pyridine bound to a NCN-Pt II -center (5a) gave a fast metathesis reaction, while the same reaction with the Pd II analogue (4a) was much slower and less selective (isomerization products were formed). Fur- thermore, it was found that 2,6-diolefin-substituted pyridines (4b, 5b, 5c) gave slow metathesis reactions, which is mainly ascribed tosteric hindrance during the ring-closing step. In all cases where prolonged reaction times were required an isomerization pro- cess, most likely assisted by cationic pincer-M II species, was observed as a competing reaction. 1 HN MR spectroscopy experiments revealed that pyridines are stronger bound to a cationic NCN-Pt II -center than toits Pd II -analogue. This aspect is of crucial importance when these pincer-pyridine complexes are applied in metathesis, since free pyridine in solution deactivates the Ru-metathesis catalyst. For the tem- plated construction of macrocycles, a strong M-N(py) bond is also important since it determines the selectivity for the desired product. In addition, these results open a new research field in which organo- metallic (pincer) complexes are used as protecting groups for strong Lewis-basic groups in catalysis. From failed attempts to prepare macrocycles using hexakis(SCS-Pd II -(1a)) complex 14, and from the results obtained with the monometallic pincer com- plexes in RCM, it can be concluded that the most suitable candidate for constructing macrocycles should comprise 2,6-diolefin-substituted pyridines bound to a multi-(NCN-Pt II )-template. In such a system, intrapyridine metathesis (steric hindrance) as well as isomerization reactions (strong M-N(py) bond) are suppressed.

Template-Directed Synthesis of Macroheterocycles by Ring-Closing Metathesis of Olefin-Substituted Pyridines in the Coordination Sphere of a Triplatinum Complex *

Mono- and tris-3,5- and 2,6-pyridinediyl-containing macroheterocycles were synthesized by metathesis of olefin-substituted pyridines in the coordination sphere of mono- and tris-platinum complexes, respectively. Tris(2,6-pyridinediyl)-containing macroheterocycles were hydrogenated over palladium catalyst. The hydrogenated macrocycle was used as ligand for the triplatinum template. The structure of the resulting complex was established by X-ray analysis.

{4-Allyloxy-2,6-bis[(dimethylamino)methyl]phenyl-κ3C1,N,N'}iodidopalladium(II)

In the title compound, [PdI(C15H23N2O)], the coordination environment of the central PdII atom is distorted squareplanar. The PdII atom is coordinated by two neutral N atoms, an anionic C atom, and an I anion with a long Pd—I distance of 2.72985 (19) Ǻ . The molecules are packed on top of each other in an antiparallel fashion via intermolecular C—H...π and C—H...O interactions.