Intermolecular and intramolecular hydrogen bonds involving fluorine atoms: implications for recognition, selectivity, and chemical properties

ChemMedChem
Claudio Dalvit, Anna Vulpetti

Abstract

A correlation between 19F NMR isotropic chemical shift and close intermolecular F⋅⋅⋅H-X contacts (with X=N or O) has been identified upon analysis of the X-ray crystal structures of fluorinated molecules listed in the Cambridge Structural Database (CSD). An optimal F⋅⋅⋅X distance involving primary and shielded secondary fluorine atoms in hydrogen-bond formation along with a correlation between F⋅⋅⋅H distance and F⋅⋅⋅H-X angle were also derived from the analysis. The hydrogen bonds involving fluorine are relevant, not only for the recognition mechanism and stabilization of a preferred conformation, but also for improvement in the permeability of the molecules, as shown with examples taken from a proprietary database. Results of an analysis of the small number of fluorine-containing natural products listed in the Protein Data Bank (PDB) appear to strengthen the derived correlation between 19F NMR isotropic chemical shift and interactions involving fluorine (also known as the "rule of shielding") and provides a hypothesis for the recognition mechanism and catalytic activity of specific enzymes. Novel chemical scaffolds, based on the rule of shielding, have been designed for recognizing distinct structural motifs present in protein...Continue Reading

References

Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
May 31, 2002·Acta Crystallographica. Section B, Structural Science·Frank H Allen
May 31, 2002·Acta Crystallographica. Section B, Structural Science·Ian J BrunoRobin Taylor
Feb 7, 2004·Nature·Changjiang DongJames H Naismith
Apr 15, 2004·Journal of the American Chemical Society·Jiangli YanEdward R Zartler
May 4, 2004·Chembiochem : a European Journal of Chemical Biology·Herbert Plenio
Jul 25, 2006·Chemistry : a European Journal·Jack D Dunitz, W Bernd Schweizer
Aug 28, 2007·Angewandte Chemie·Roman LeistWim Klopper
Sep 29, 2007·Science·Klaus MüllerFrançois Diederich
Nov 23, 2007·Journal of the American Chemical Society·Charles E McKennaSamuel H Wilson
Jan 17, 2008·Chemical Society Reviews·David O'Hagan
Oct 1, 2008·Chembiochem : a European Journal of Chemical Biology·Hannes KopitzHolger Gohlke
Aug 26, 2009·Journal of the American Chemical Society·Anna VulpettiClaudio Dalvit
Feb 23, 2010·Journal of Medicinal Chemistry·Morteza MalakoutikhahErnest Giralt
Feb 24, 2010·Journal of Medicinal Chemistry·Bernd KuhnMartin Stahl
May 1, 2010·The Journal of Biological Chemistry·Marcio V B DiasTom L Blundell
Sep 8, 2010·Physical Chemistry Chemical Physics : PCCP·G N Manjunatha ReddyN Suryaprakash
Oct 30, 2010·Angewandte Chemie·Gautam R Desiraju
Apr 23, 2011·Journal of the American Chemical Society·Peter W Y ChanEmil F Pai
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Sarah F JenkinsonAmber L Thompson
Sep 23, 2011·Journal of Medicinal Chemistry·Ed GriffenDaniel J Warner

Citations

Apr 7, 2012·Drug Discovery Today·Anna Vulpetti, Claudio Dalvit
Jul 22, 2014·Chemistry : a European Journal·Claudio DalvitAnna Vulpetti
May 13, 2014·Chemical Biology & Drug Design·Eleanor W W LeungRaymond S Norton
Apr 16, 2015·Future Medicinal Chemistry·Marcella BassettoFabrizio Pertusati
Sep 26, 2012·Bioorganic & Medicinal Chemistry Letters·Prashant V DesaiMaria-Jesus Blanco
Apr 22, 2015·Journal of Medicinal Chemistry·Konrad HohlfeldJohan Unge
Dec 2, 2016·Chemistry : a European Journal·Jerome GratonBruno Linclau
Feb 23, 2018·Antibiotics·Zorik ChilingaryanAaron J Oakley
Aug 21, 2018·Chemistry : a European Journal·Daniel O'ReillyMasad J Damha
Jan 20, 2019·Medicinal Research Reviews·Giulia CaronGiuseppe Ermondi
Apr 18, 2012·Beilstein Journal of Organic Chemistry·Michaela BraitschWalther Schmid
May 2, 2021·Bioorganic & Medicinal Chemistry·Hui QiuBrian Sherer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Nodding Syndrome

Nodding Syndrome is a neurological and epileptiform disorder characterized by psychomotor, mental, and growth retardation. Discover the latest research on Nodding Syndrome here.

LRRK2 & Microtubules

Mutations in the LRRK2 gene are risk-factors for developing Parkinson’s disease (PD). LRRK2 mutations in PD have been shown to enhance its association with microtubules. Here is the latest research.