Fluorine Fragment Cocktails are specifically designed to accelerate fragment-based drug discovery (FBDD) using ¹⁹F-assisted NMR screening. Pooling and combining carefully selected fluorinated fragments into predefined cocktails with well-separated ¹⁹F chemical shifts enables rapid high-throughput hit identification and at the same time, straightforward spectrum interpretation. Thus, it proves to be an efficient way to explore a broader chemical space and identify initial starting points for subsequent drug development.
Compared to screening individual fragments, ¹⁹F NMR fragment cocktails allow simultaneous screening of multiple compounds without signal overlap, significantly increasing screening efficiency and expanding the chemically diverse fragment space to explore. The absence of endogenous fluorine in biological systems, together with the high sensitivity and broad chemical shift dispersion of the ¹⁹F nucleus, makes this approach particularly attractive for early hit discovery, even in laboratories with standard NMR instrumentation.
Rationally Designed for Reliable ¹⁹F NMR Screening
Life Chemicals has developed a unique collection of 173 predefined Fluorine Fragment Cocktails, each containing 10 structurally diverse fluorinated fragments selected to maximize separation of their ¹⁹F NMR chemical shifts. This rational cocktail design minimizes spectral overlap and enables rapid identification of fragment binders by comparing protein-bound and reference spectra.
All fragments were selected using comprehensive medicinal chemistry filtering to ensure:
- wider structural diversity and extensive chemical space coverage
- varying fluorine chemical environments
- experimentally confirmed solubility in both DMSO and phosphate-buffered saline (PBS)
- high suitability for fragment-based drug discovery
The resulting Screening Set offers up to 1,730 in-stock fluorinated drug-like fragments from the proprietary Fluorine Fragment Library.
Fragment Selection Criteria
Each fragment satisfies stringent quality criteria:
- single fluorine-containing functional group
- typically a single, well-resolved ¹⁹F NMR signal per compound
- free from reactive, unstable and undesirable structural motifs
- DMSO solubility up to 200 mM
- PBS solubility ≥ 0.1 mM
- purity above 90 %
Physicochemical Profile
- Molecular weight: 130-300 Da
- cLogP: -2.6 to 3.9
- Hydrogen bond donors: ≤ 4
- Hydrogen bond acceptors: ≤ 5
- Rotatable bonds: ≤ 10
- TPSA: ≤ 120 Ų
Available Formats
The Fluorine Fragment Cocktails are available in several convenient formats suitable for different ¹⁹F NMR screening workflows.
For customers seeking a ready-to-screen solution, we offer an assay-ready Pre-plated Fluorine Fragment Cocktail Set, supplied in various plate formats (see the dedicated product page for details).
Alternatively, individual fluorinated fragments are provided as:
- solid compounds or DMSO/DMSO-d6 solutions
- standard solution concentrations of 100 mM or 200 mM
- custom solution concentrations, plate layouts and formatting
- predefined fragment cocktails
Please note: As fragments are supplied from our continuously updated in-stock collection, compound availability may change over time. Please contact the Life Chemicals team to obtain the latest compound list and current stock availability.
Please, contact us at orders@lifechemicals.com for any additional information and price quotations.
Figure 1. Distribution of compounds by different types of fluorine-substituted groups
Examples of the fluorine-containing fragments from the Fluorine Fragment Cocktails
Cocktail #2
Cocktail #85
Cocktail #160
References
- Nagatoishi S, Yamaguchi S et al. Bioorg Med Chem. 2018 May 1; 26(8):1929-1938.
- Norton, R.; Leung, E.; Chandrashekaran, I.; MacRaild, C. Molecules 2016, 21 (7), 860.
- Nosik, P. S., Gerasov, A. O. et al. Adv. Synth. Catal. 359 (2017), 3126-3136
- Gerasov, A., Dolgonos, G. A. et al. Synthesis (Stuttg). Published online: 2020 Jan.