Polar Tris(pyrazolyl)borates for the modeling of Zinc metalloenzymes in aqueous solution

The ultimate aim of this work was to understand the importance of secondary interactions of hydrophilic nature in the catalytic activity of zinc metalloenzymes. The zinc complexes of novel poly(pyrazolyl)borate ligands bearing polar substituents on the 3-position of the pyrazoles were expected to contribute to this. These comprise the carboxyester substituted BpC(O)OR,Me (R = Me, Et), the pyridyl substituted Tp4'Py,Me and Tp4'(6'Me)Py,Me, and the carboxyamide substituted TpC(O)NHPh,Me ligands. <br>The water soluble BpC(O)OR,Me (R = Me, Et) ligands were isolated as their potassium and thallium salts. They build the bis(ligand) complexes (BpC(O)OR,Me)2Zn with zinc salts of poorly coordinating counter ions, and can undergo self-transesterification in alcoholic solutions. The bis(pyrazolyl)borate BpPh,Me was also prepared and showed to behave similarly towards zinc. Carboxyester substituted pyrazoles HpzMe,C(O)OR were revealed not to be good precursors of the corresponding tris(pyrazolyl)borates TpC(O)OR,Me. <br>The new 4'-pyridyl substituted KTp4'Py,Me and KTp4'(6'Me)Py,Me were synthesized, the former being the first example of water soluble tris(pyrazolyl)borate able to build a hydrophobic cavity around zinc. The zinc halide, acetate and nitrate complexes of Tp4'Py,Me showed the versatile coordination behaviour of Tp4'Py,Me towards zinc and its hydrophilic character. The novel aqua and methanol complexes [Tp4'Py,MeZn·OH2]ClO4 and [Tp4'Py,MeZn·HOMe]ClO4 were revealed to form dimeric species in the solid state due to pyridine coordination to zinc, and to interact with the solvent molecules in a similar manner as it occurs in the resting state of zinc metalloenzymes. [Tp4'Py,MeZn·OH2]ClO4 was found to be an appropriate reagent for the cleavage of tris(o-dichlorophenyl)phosphate, tris(p-nitrophenyl)phosphate, trifluoro(p-nitrophenyl) acetate and p-nitrophenylacetate, in aqueous solution, and was also demonstrated to behave as a catalyst in the hydrolysis of tris(p-nitrophenyl)phosphate. The carbonic anhydrase catalysed hydration of CO2 was modelled by the insertion reactions of the new hydroxo complex Tp4'Py,MeZn-OH with CO2 and CS2 in alcoholic solutions, thereby obtaining a mixed methylcarbonate-chloride complex and two alkylxanthogenate complexes. The new beta-ketoenolate complexes Tp4'Py,MeZn(acac) and Tp4'Py,MeZn(benzoylac) provided new examples of "transition state analogues" of zinc containing metalloproteases. The biologically relevant hydrolytic cleavages of phosphotriesters and carboxyesters were also modelled with Tp4'Py,MeZn-OH, thereby obtaining the new p-nitrophenolate and bis(p-nitrophenyl)phosphate complexes, Tp4'Py,MeZn-ONit and Tp4'Py,MeZn-OP(O)(ONit)2. The hydroxo complex did not promote the hydrolytic cleavage of carboxyamides, but the deprotonation of trifluoroacetamide to give Tp4'Py,MeZn-NHC(O)CF3. <br>Finally, the ligand TpC(O)NHPh,Me incorporating for the first time NH hydrogen donor groups in a pyrazolylborate system, was isolated as its potassium salt, which is soluble in alcohol/water mixtures. The zinc halide, acetate and nitrate complexes of TpC(O)NHPh,Me were isolated and spectroscopically characterized. The X-ray crystal structure determination of the new hydroxide bridged binuclear complex [(TpC(O)NHPh,MeZn)2(OH)]ClO4 revealed the existence of a series of secondary interactions of hydrophobic and hydrophilic nature, which are influencing the chemistry of TpC(O)NHPh,Me based zinc complexes as they do in the active sites of zinc metalloenzymes. <br>In summary, 3 new bis(pyrazolyl)borate and 3 novel polar tris(pyrazolyl)borate ligands were synthesized. 7 potassium, 2 thallium and 25 zinc complexes were isolated. 12 compounds were structurally characterized.

Author dc:creator

• Pérez Olmo, Cristina

Contributors dc:contributor

• Vahrenkamp, Heinrich

• Biomimetische Chemie
• Zink Modellkomplexe
• Ligandentwicklung
• Trispyrazolylborate
• Zinkenzymen
• Biomimetic chemistry
• Zinc modelcomplexes
• ligand design
• Trispyrazolylborates
• Zinc enzymes

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https://freidok.uni-freiburg.de/data/1770

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:1770