17078-34-1

Upstream product

• 944-43-4 4-amino-2,3,5,6-tetrafluorobenzoic acid 
• 126695-59-8 4-(hydroxymethyl)-2,3,5,6-tetrafluorophenyl azide 
• 120384-18-1 4-azido-2,3,5,6-tetrafluorobenzaldehyde 
• 653-37-2 perfluorobenzaldehyde 
• 440-60-8 (2,3,4,5,6-pentafluorophenyl)methanol 

Downstream Products

• 126695-59-8 4-(hydroxymethyl)-2,3,5,6-tetrafluorophenyl azide 
• 119060-58-1 4-amino-2,3,5,6-tetrafluorobenzyl aldehyde 

Relevant academic research and scientific papers

Tetrafluoroaryl azide as an N-Terminal capping group for click-To-dissolve diphenylalanine hydrogels

The synthesis of a bioorthogonal-responsive low molecular weight diphenylalanine (PhePhe)-based hydrogel that is capped with a 4-Azido-2,3,5,6-Tetrafluorobenzyl carbamate self-immolative linker is reported. The hydrogelator (AzF4-PhePhe) generates a stable hydrogel at 0.1 wt%, and rapidly reacts with the bioorthogonal reagent trans-cyclooctene (TCO), inducing a gel-To-solution transition. The critical gel concentration is five-fold lower than our previously synthesized non-fluorinated hydrogelator (Az-PhePhe), and the minimum concentration of TCO required for visible gel-To-solution transition in 24 hours is 1 mM. Doxorubicin can be encapsulated in the hydrogel and TCO-Triggered dissolution results in 76% and 89% release after 10 and 24 hours, respectively. Compared with our non-substituted aryl azide capping group used for Az-PhePhe, the tetrafluorinated aryl azide group improves the stability of the hydrogel in unbuffered water at a lower critical gel concentration, while improving sensitivity towards the bioorthogonal reagent TCO.

Polyfluorinated hydroxy and carboxy benzenes as a new type of H-donors for self-assembly with 18-crown-6 ether: Synthesis, supramolecular structure and stability of co-crystals

Potential of polyfluoroaromatic compounds containing OH, COOH, and mixed H-donor functions as co-formers in co-crystallization with 18-crown-6 ether was explored. Pentafluorophenol, 1,3- and 1,4-dihydroxytetrafluorobenzenes and pentafluorobenzoic acid form with 18-crown-6 hydrated co-crystals containing one water molecule per H-donor group upon contact of the solutions with atmospheric moisture; pentafluorophenol gives a co-crystal with double the amount of water in aqueous EtOH. Aminotetrafluorobenzyl alcohol and aminotetrafluorobenzoic acid are capable of forming anhydrous 1:1 and 2:1 co-crystals with 18-crown-6. In the crystalline hydrates, co-formers molecules are connected via water-mediated synthon [C(O)]O[sbnd]H?O(H)[sbnd]H?Ocr. According to quantum chemical calculations, the participation of each water linker molecule in H-bonding increases the stability of the supramolecular structure by about 100 kJ mol?1. Associates of bifunctional arenes exhibit H-bonded 1D assembly as an only structure-determining motif; molecules of monofunctional arenes in the co-crystals are bound via πF?πF stacking to give the H-bonded/π-stacked 1D assembly. The calculated π-stacking energy depends on the nature of the H-donor function (NH2, OH, COOH), decreasing with a decrease in the molecule dipole moment.

Switching on prodrugs using radiotherapy

Chemotherapy is a powerful tool in the armoury against cancer, but it is fraught with problems due to its global systemic toxicity. Here we report the proof of concept of a chemistry-based strategy, whereby gamma/X-ray irradiation mediates the activation of a cancer prodrug, thereby enabling simultaneous chemo-radiotherapy with radiotherapy locally activating a prodrug. In an initial demonstration, we show the activation of a fluorescent probe using this approach. Expanding on this, we show how sulfonyl azide- and phenyl azide-caged prodrugs of pazopanib and doxorubicin can be liberated using clinically relevant doses of ionizing radiation. This strategy is different to conventional chemo-radiotherapy radiation, where chemo-sensitization of the cancer takes place so that subsequent radiotherapy is more effective. This approach could enable site-directed chemotherapy, rather than systemic chemotherapy, with ‘real time’ drug decaging at the tumour site. As such, it opens up a new era in targeted and directed chemotherapy. [Figure not available: see fulltext.].

Azido-Functionalized Aromatic Phosphonate Esters in RPOSS-Cage-Supported Lanthanide Ion (Ln = La, Nd, Dy, Er) Coordination

Within this work, a modified preparation of diethyl 4-azidobenzylphosphonate (L1) is presented and the family of 4- or 4′-azido-substituted aromatic phosphonate esters is increased by three new ligand platforms: diisopropyl 4-azidobenzylphosphonate (L2), diisopropyl ((4′-azido-[1,1′-biphenyl]-4-yl)methyl)phosphonate (L3), and diisopropyl 4-azido-2,3,5,6-tetrafluorobenzylphosphonate (L4), which exhibit an anomalous splitting of the N3 stretching vibrations. Subsequent coordination to the in situ generated RPOSS (polyhedral oligomeric silsesquioxane)-cage-supported lanthanide precursors [(Ln{RPOSS})2(THF)m] (P1-P6) (Ln = La, Nd, Dy, Er; R = iBu, Ph; m = 0, 1) yields complexes of the general formula [Ln{RPOSS}(L1-L4)n(S1)x(THF)m] (1-30) (n = 2, 3; x = 0, 1; m = 0-2) retaining the azide unit for future semiconductor surface immobilization. Because the latter compounds are mostly oils or viscous waxes, preliminary solution-state structure elucidations via DOSY-ECC-MW estimations have been carried out which are in accordance with 1H NMR integral ratios as well as solid-state structures, where available. Moreover, the optical properties of the Nd, Dy, and Er derivatives of complexes 1-30 are examined in the visible and NIR spectral regions, where applicable.

Mechanistic Evaluation of Bioorthogonal Decaging with trans-Cyclooctene: The Effect of Fluorine Substituents on Aryl Azide Reactivity and Decaging from the 1,2,3-Triazoline

Bioorthogonal prodrug activation/decaging strategies need to be selective, rapid and release the drug from the masking group upon activation. The rates of the 1,3-dipolar cycloaddition between a trans-cyclooctene (TCO) and a series of fluorine-substituted