Surface-confined Ullmann coupling of thiophene substituted porphyrins.

The covalent coupling of (5,10,15,20-tetrabromothien-2-ylporphyrinato)zinc(II) (TBrThP) molecules on the Ag(111) surface has been investigated under ultra-high-vacuum conditions, using scanning tunnelling microscopy and x-ray photoelectron spectroscopy. The findings provide atomic-level insight into surface-confined Ullmann coupling of thiophene substituted porphyrins, analyzing the progression of organometallic intermediate to final coupled state. Adsorption of the TBrThP molecules on the Ag(111) surface at room temperature is found to result in the reductive dehalogenation of the bromothienyl substituents and the subsequent formation of single strand and crosslinked coordination networks. The coordinated substrate atoms bridge the proximal thienyl groups of the organometallic intermediate, while the cleaved bromine atoms are bound on the adjacent Ag(111) surface. The intermediate complex displays a thermal lability at ∼423 K that results in the dissociation of the proximal thienyl groups with the concomitant loss of the surface bound bromine. At the thermally induced dissociation of the intermediate complex the resultant thienylporphyrin derivatives covalently couple, leading to the formation of a polymeric network of thiophene linked and meso-meso fused porphyrins.

Designed multiple ligands for cancer therapy.

The concept of a single chemical entity with desirable activity at more than one biological target is an attractive one. Increasingly, multiple complex biochemical pathways are implicated in a variety of diseases including cancer. Successful treatment of these conditions often depends on pharmaceutical intervention at multiple pathways, with a combination of different drugs. Designed multiple ligands (DMLs) are drugs which act at multiple biomolecular targets. Numerous terms have been used to describe such ligands, including multiple-target directed ligands, heterodimers, promiscuous drugs and pan-agonists. However, although there are many reported examples of multiple-targeting anti-cancer agents, no review of these has been presented to date. A huge variety of biological signalling-pathways, proteins and enzymes are currently targeted and implicated in the pathogenesis of cancer. This review will provide an overview of reported designed multiple ligands for cancer and an exploration of the advantages and drawbacks of such compounds. The review also provides brief commentaries on the biological processes and proteins that are currently targeted in cancer therapy and the potential for dual or triple targeting of these with designed multiple ligands.