It has become evident that fluorinated compounds have a remarkable record in medicinal chemistry and will play a continuing role in providing lead compounds for therapeutic applications. This tutorial review provides a sampling of renowned fluorinated drugs and their mode of action with a discussion clarifying the role and impact of fluorine substitution on drug potency.

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Fluorine in medicinal chemistry.

The Huisgen 1,3-dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attention in recent years due to the introduction in 2001 of Cu(1) catalysis by Tornoe and Meldal, leading to a major improvement in both rate and regioselectivity of the reaction, as realized independently by the Meldal and the Sharpless laboratories. The great success of the Cu(1) catalyzed reaction is rooted in the fact that it is a virtually quantitative, very robust, insensitive, general, and orthogonal ligation reaction, suitable for even biomolecular ligation and in vivo tagging or as a polymerization reaction for synthesis of long linear polymers. The triazole formed is essentially chemically inert to reactive conditions, e.g. oxidation, reduction, and hydrolysis, and has an intermediate polarity with a dipolar moment of ∼5 D. The basis for the unique properties and rate enhancement for triazole formation under Cu(1) catalysis should be found in the high ∆G of the reaction in combination with the low character of polarity of the dipole of the noncatalyzed thermal reaction, which leads to a considerable activation barrier. In order to understand the reaction in detail, it therefore seems important to spend a moment to consider the structural and mechanistic aspects of the catalysis. The reaction is quite insensitive to reaction conditions as long as Cu(1) is present and may be performed in an aqueous or organic environment both in solution and on solid support.

Cu-catalyzed azide-alkyne cycloaddition.

A superhydrophobic surface is a surface with a water contact angle close to or higher than 150°. In this feature article, we review the historical and present research on superhydrophobic surfaces, including the characterization of superhydrophobicity, different ways to fabricate rough surfaces, and low-surface-energy modifications on inorganic and organic rough surfaces. It is the combination of surface roughness and low-surface-energy modification that leads to superhydrophobicity. Notably, research on superhydrophobic surfaces has not only fundamental interest but various possible functional applications in micro- and nano-materials and devices.

Superhydrophobic surfaces: from structural control to functional application

In 2001, Sharpless and co-workers introduced "click" chemistry, a new approach in organic synthesis that involves a handful of almost perfect chemical reactions. Among these carefully selected reactions, Huisgen 1,3-dipolar cycloadditions were shown to be the most effective and versatile and thus became the prime example of click chemistry. Hence, these long-neglected reactions were suddenly re-established in organic synthesis and, in particular, have gained popularity in materials science. The number of publications dealing with click chemistry has grown exponentially over the last two years. The Minireview discusses whether click chemistry is a miracle tool or an ephemeral trend.

1,3‐Dipolar Cycloadditions of Azides and Alkynes: A Universal Ligation Tool in Polymer and Materials Science

“All new is well-forgotten old”, the proverb goes. The current “fluorine boom” is news only to a novice in the field: the exceptional importance of fluorinated organic compounds in numerous areas has been known for a long time. The sharpest increase in the number of fluorine-containing pharmaceuticals and agrochemicals is dated back to 30 years ago. Also around that time (1979), the first monograph devoted to industrial applications of organofluorine compounds was published, covering not only fluorine-containing biologically active materials but also refrigerants, propellants, surfactants, textile chemicals, polymers, and dyes. The increasingly broad realization of the key role of organofluorine compounds in numerous areas has recently attracted many new scientists to the field. The development of new methods for the selective introduction of fluorine and fluorinecontaining groups into organic molecules for biologically active and other useful materials has become a hot area. Over 100 reviews, book chapters, and highlights on this subject have appeared in the literature in the past few years. As citing all of these publications in this review article is impossible, we provide references to only the most recent, general, and comprehensive ones. Molecules bearing a trifluoromethyl group constitute one of the most important classes of selectively fluorinated compounds. As early as 1928, Lehmann reported his observations of biological activity of some trifluoromethylated organic derivatives and already in 1959 Yale published a detailed review article entitled “The Trifluoromethyl Group in Medicinal Chemistry”. Since then, numerous books and reviews have appeared in the literature covering various aspects of trifluoromethylated organic and organometallic compounds. Within this family, derivatives bearing the CF3 group on aromatic rings are particularly numerous and important. Some examples of such compounds used as active ingredients of pharmaceuticals and agrochemicals are shown in Scheme 1. Trifluoromethylated building blocks and intermediates are clearly needed to make such molecules. The simplest trifluoromethylated aromatic compound, benzotrifluoride, was originally prepared by Swarts at the end of the 19th century. In his work, Swarts treated benzotrichloride with “two thirds of its weight of antimony fluoride” to obtain a mixture of PhCF2Cl and PhCF3, from which the two were separated and isolated pure by distillation. In the early 1930s, two industrial groups, one from Kinetic Chemicals, Inc. and one from I. G. Farbenindustrie AG patented their discoveries on the successful use of HF instead of SbF3 for the Swarts reaction. These inventions were the starting point for the modern large-scale manufacturing of trifluoromethylated aromatics. Other methods have been developed for conversion of various C1 units on the ring to CF3 with a variety of fluorinating agents. While representing an outstanding discovery and a classic of organic and organofluorine chemistry, the Swarts reaction is nonetheless neither atom-economical nor environmentally benign, as it deals with stoichiometric quantities of hazardous chemicals and generates large amounts of chlorine waste. To convert a CH3 group on the ring to CF3, the methyl is first exhaustively chlorinated to produce 3 equiv of HCl as a

Aromatic Trifluoromethylation with Metal Complexes

Superhydrophobic cotton fabric coating based on a complex layer of silica nanoparticles and perfluorooctylated quaternary ammonium silane coupling agent

Wei-Dong Meng

Papers

Superhydrophobic cotton fabric coating based on a complex layer of silica nanoparticles and perfluorooctylated quaternary ammonium silane coupling agent

Synthesis of fluorinated amino acids

Synthesis and anticancer effect of chrysin derivatives

Synthesis and repellent properties of vinylidene fluoride-containing polyacrylates

Novel perfluorocyclobutyl (PFCB)-containing polymers formed by click chemistry