The electronic properties and relatively small size of fluorine endow it with considerable versatility as a bioisostere and it has found application as a substitute for lone pairs of electrons, the hydrogen atom, and the methyl group while also acting as a functional mimetic of the carbonyl, carbinol, and nitrile moieties. In this context, fluorine substitution can influence the potency, conformation, metabolism, membrane permeability, and P-gp recognition of a molecule and temper inhibition of the hERG channel by basic amines. However, as a consequence of the unique properties of fluorine, it features prominently in the design of higher order structural metaphors that are more esoteric in their conception and which reflect a more sophisticated molecular construction that broadens biological mimesis. In this Perspective, applications of fluorine in the construction of bioisosteric elements designed to enhance the in vitro and in vivo properties of a molecule are summarized.

Fluorine and Fluorinated Motifs in the Design and Application of Bioisosteres for Drug Design.

π-Bonding and the Lone Pair Effect in Multiple Bonds between Heavier Main Group Elements

This review is essentially an update of one entitled “πBonding and The Lone Pair Effect in Multiple Bonds Between Heavier Main Group Elements” which was published more than 10 years ago in this journal.1 The coverage of that survey was focused on the synthesis, structure, and bonding of stable compounds2 of heavier main group elements that correspond to the skeletal drawings reproduced in Tables 1 and 2. A row of numbers is listed at the bottom of each column in these tables. This refers to the number of stable complexes from each class that are currently known. The numbers in parentheses refer to the number of stable species that were known at the time of the previous review. Clearly, many of the compound classes listed have undergone considerable expansion although some remain stubbornly rare. The most significant developments for each class will be discussed in detail under the respective sections. As will be seen, there are also a limited number of multiple bonded heavier main group species that do not fit neatly in the classifications in Tables 1 and 2. However, to keep the review to a manageable length, the limits and exclusions, which parallel those used earlier, are summarized as follows: (i) discussion is mainly confined to compounds where experimental data on stable, isolated species have been obtained, (ii) stable compounds having multiple bonding between heavier main group elements and transition metals are not generally discussed, (iii) compounds in which a multiple bonded heavier main group element is incorporated within a ring are generally not covered, and (iv) hypervalent main group compounds that may incorporate faux multiple bonding are generally excluded. Such compounds are distinguished from those in Tables 1 and 2 in that they apparently require the use of more than four valence bonding orbitals at one or more of the bonded atoms. The remainder of this review is organized in a similar manner to that of the previous one wherein the compounds to be discussed are classified according to those summarized in Tables 1 and 2. The key unifying feature of almost all molecules discussed in this review is that they are generally stabilized by the use of bulky substituents which block associative or various decomposition pathways.3 Since the previous review was published in 1999, several review articles that cover parts of the subject matter have appeared.4

π-Bonding and the Lone Pair Effect in Multiple Bonds Involving Heavier Main Group Elements: Developments in the New Millennium

Main-Group Element, Organic, and Organometallic Derivatives of Polyoxometalates.

Recent developments in the stereoselective synthesis of α-aminoacids

Electrolysis of 1,1,2,2-tetracyanocyclopropanes in alcohols in undivided cells leads to 2-amino-4,4-dialkoxy-1,5-dicyano-3-azabicyclo[3.1.0]hex-2-enes after 0.05–0.20 F mol−1 of electricity has been passed.

Electrocatalytic Transformation of 1,1,2,2-Tetracyanocyclopropanes into Bicyclic Pyrrolines.

The structure of the condensation product of phthalonitrile and phenol is found by x-ray structure analysis. The structure of a new class of polyheteroarylenes, polhydroxyphenylisoindazenes, is defined using the data obtained.

Crystal and molecular structure of 1,1-bis(hydroxyphenyl)-3-ketoisoindoline

An x-ray structural study has shown that the nature of the steric distortions in [2,2]paracyclophane remains practically unchanged when Br-substituents are introduced into positions 4 and 15.

Molecular structure of 4,15-dibromo[2.2]paracyclophane

4− and 8-membered phosphazanes with 5-membered cycles containing phosphorus have been synthesized by disamination of spirophosphoranes and phosphorylation of aminoketones with primary amino group by means of PCI3. The structural investigation of the above mentioned phosphazanes was carried out.

Four- and Eight-Membered Phosphazanes with Five-Membered Fragments

The validity of syn- and anti-isomer assignments in the case of 3Β,21-diacetoxypregna-5, 16-dien-20-one 20-carboethoxyhydrazones has been established by x-ray structural analysis; the isomer designations had been made previously based on chemical and spectral data. The isomers differ sharply in the conjugative relationship between the hydrazone group and the C16=C17 double bond in the steroid skeleton: the syn-isomer is trans-conjugated (the degree of twisting about the C17-C20 bond is characterized by a torsional angleψ=-161.0‡), while the anti-isomer is not conjugated (ϕ=− 75.3‡); this explains the electronic spectral features of these isomers.

Yuri T. Struchkov

Papers

Electrocatalytic Transformation of 1,1,2,2-Tetracyanocyclopropanes into Bicyclic Pyrrolines.

Crystal and molecular structure of 1,1-bis(hydroxyphenyl)-3-ketoisoindoline

Molecular structure of 4,15-dibromo[2.2]paracyclophane

Four- and Eight-Membered Phosphazanes with Five-Membered Fragments

Molecular structures of syn- and anti-20-carboethoxyhydrazone isomers of 3Β, 21-diacetoxypregna-5,16-dien-20-one