Halogenated ligands and their interactions with amino acids: Implications for structure–activity and structure–toxicity relationships

Halogen–water–hydrogen bridges in biomolecules

“…In the drug design procedure halogenation of pharmacologically active compounds is a common strategy to improve their metabolic stability and lipophilicity and to alter their electronic properties (Kortagere et al, 2008). In recent years, dozens of crystallographic evidences uncovered that the ligand's halogen atoms can directly participate in X-bonding interactions with protein receptors, and these interactions are responsible for the affinity and specificity of ligand binding (Himmel et al, 2005;Jiang et al, 2006).…”

“…1, the energy variation of X-bonding is very close to that of H-bonding: the both spans over a very wide range from almost 0 to 40 kcal/mol. Since X-bonding has been demonstrated to play important roles in biological systems, for example, it assists protein kinase-inhibitor binding , directs DNA conformation , and mediates biological toxicity (Kortagere et al, 2008), we speculate that the XWH bridges also widely exist in biomolecules and conduct diverse biological effects. Previously, a systematic survey of X-bonds in Protein Data Bank (PDB) (Berman et al, 2000) shed some light into the characteristics of short halogen-water contacts in biomolecules (Auffinger et al, 2004).…”

Analytical methods for the determination of halogens in bioanalytical sciences: a review

“…The biological effects of halogens, in their anionic form (as fluoride, bromide, chloride, and iodide) can be less dangerous in comparison with those of organic halogenated compounds [7,15,16]. Nevertheless, halogen-containing organic compounds have been largely used in many industrial applications, resulting in great public concern because many of them are toxic, persistent, and subject to bioaccumulation in food chains [7,15,17].…”

“…However, this approach can sometimes result in molecules that have undesirable effects or even toxicity [16]. Some of the reported effects for halogens as ions or halogenated organic contaminants and their main properties are presented in Table 1.…”

Halodiazoacetates as useful tools for selective halo-functionalization

“…Several halogenated natural products have therapeutic interest [5], and new examples are continuously discovered. The frequent utilization of fluoro-and chloro-substituents in drug design further illustrates the ability of halogens to modulate selectivity, enzymatic stability, and/or affinity of pharmaceutically active compounds [6,7]. The immense importance of alkyl halides in organic synthesis needs no explanation; substitution reactions, coupling chemistry, the list of valuable reactions is long.…”