Pyrroloquinoline Quinone Aza-Crown Ether Complexes as Biomimetics for Lanthanide and Calcium Dependent Alcohol Dehydrogenases**

Understanding the role of metal ions in biology can lead to the development of new catalysts for several industrially important transformations. Lanthanides are the most recent group of metal ions that have been shown to be important in biology, that is, in quinone-dependent methanol dehydrogenases (MDH). Here we evaluate a literature-known pyrroloquinoline quinone (PQQ) and 1-aza-15-crown-5 based ligand platform as scaffold for Ca$^{2+}$, Ba$^{2+}$, La$^{3+}$ and Lu$^{3+}$ biomimetics of MDH and we evaluate the importance of ligand design, charge, size, counterions and base for the alcohol oxidation reaction using NMR spectroscopy. In addition, we report a new straightforward synthetic route (3 steps instead of 11 and 33 % instead of 0.6 % yield) for biomimetic ligands based on PQQ. We show that when studying biomimetics for MDH, larger metal ions and those with lower charge in this case promote the dehydrogenation reaction more effectively and that this is likely an effect of the ligand design which must be considered when studying biomimetics. To gain more information on the structures and impact of counterions of the complexes, we performed collision induced dissociation (CID) experiments and observe that the nitrates are more tightly bound than the triflates. To resolve the structure of the complexes in the gas phase we combined DFT-calculations and ion mobility measurements (IMS). Furthermore, we characterized the obtained complexes and reaction mixtures using Electron Paramagnetic Resonance (EPR) spectroscopy and show the presence of a small amount of quinone-based radical

Impact of the lanthanide contraction on the activity of a lanthanide-dependent methanol dehydrogenase - a kinetic and DFT study

Interest in the bioinorganic chemistry of lanthanides is growing rapidly as more and more lanthanide-dependent bacteria are being discovered. Especially the earlier lanthanides have been shown to be preferentially utilized by bacteria that need these Lewis acids as cofactors in their alcohol dehydrogenase enzymes. Here, we investigate the impact of the lanthanide ions lanthanum(III) to lutetium(III) (excluding Pm) on the catalytic parameters (v(max), K-M, k(cat)/K-M) of a methanol dehydrogenase (MDH) isolated from Methylacidiphilum fumariolicum SolV. Kinetic experiments and DFT calculations were used to discuss why only the earlier lanthanides (La-Gd) promote high MDH activity. Impact of Lewis acidity, coordination number preferences, stability constants and other properties that are a direct result of the lanthanide contraction are discussed in light of the two proposed mechanisms for MDH

The Earlier the Better: Structural Analysis and Separation of Lanthanides with Pyrroloquinoline Quinone

Lanthanides (Ln) are critical raw materials, however, their mining and purification have a considerable negative environmental impact and sustainable recycling and separation strategies for these elements are needed. In this study, the precipitation and solubility behavior of Ln complexes with pyrroloquinoline quinone (PQQ), the cofactor of recently discovered lanthanide (Ln) dependent methanol dehydrogenase (MDH) enzymes, is presented. In this context, the molecular structure of a biorelevant europium PQQ complex was for the first time elucidated outside a protein environment. The complex crystallizes as an inversion symmetric dimer, Eu2PQQ2, with binding of Eu in the biologically relevant pocket of PQQ. LnPQQ and Ln1Ln2PQQ complexes were characterized by using inductively coupled plasma mass spectrometry (ICP‐MS), infrared (IR) spectroscopy, 151Eu‐Mössbauer spectroscopy, X‐ray total scattering, and extended X‐ray absorption fine structure (EXAFS). It is shown that a natural enzymatic cofactor is capable to achieve separation by precipitation of the notoriously similar, and thus difficult to separate, lanthanides to some extent

Crystal structure of a calcium(II)–pyrroloquinoline quinone (PQQ) complex outside a protein environment

Pyrroloquinoline quinone (PQQ) is an important cofactor of calcium‐ and lanthanide‐dependent alcohol dehydrogenases, and has been known for over 30 years. Crystal structures of Ca–MDH enzymes (MDH is methanol dehydrogenase) have been known for some time; however, crystal structures of PQQ with biorelevant metal ions have been lacking in the literature for decades. We report here the first crystal structure analysis of a Ca–PQQ complex outside the protein environment, namely, poly[[undecaaquabis(μ‐4,5‐dioxo‐4,5‐dihydro‐1H‐pyrrolo[2,3‐f]quinoline‐2,7,9‐tricarboxylato)tricalcium(II)] dihydrate], {[Ca3(C14H3N2O8)2(H2O)11]·2H2O}n. The complex crystallized as Ca3PQQ2·13H2O with Ca2+ in three different positions and PQQ3−, including an extensive hydrogen‐bond network. Similarities and differences to the recently reported structure with biorelevant europium (Eu2PQQ2) are discussed.Pyrroloquinoline quinone (PQQ) is an important cofactor of calcium‐ and lanthanide‐dependent alcohol dehydrogenases. The crystal structure of a Ca–PQQ complex (Ca3PQQ2·13H2O) is reported for the first time outside a protein environment. imageresearc

Impact of the lanthanide contraction on the activity of a lanthanide-dependent methanol dehydrogenase - a kinetic and DFT study

Contains fulltext : 194811.pdf (publisher's version ) (Open Access

PQQ-Aza-Crown Ether Complexes as Biomimetics for Lanthanide and Calcium Dependent Alcohol Dehydrogenases

Understanding the role of metal ions in biology can lead to the development of new catalysts forseveral industrially important transformations. Lanthanides are the most recent group of metal ionsthat have been shown to be important in biology i.e. - in quinone-dependent methanoldehydrogenases (MDH). Here we evaluate a pyrroloquinoline quinone and 1-aza-15-crown-5 basedligand platform as scaffold for Ca2+ , Ba2+ , La3+ and Lu3+ biomimetics of MDH and we evaluate theimportance of ligand design, charge, size, counterions and base for the alcohol oxidation reactionusing NMR spectroscopy. In addition, we report a new straightforward synthetic route (3 stepsinstead of 11 and 33% instead of 0.6% yield) for biomimetic ligands based on PQQ. We show thatwhen studying biomimetics for MDH, larger metal ions and those with lower charge in this casepromote the dehydrogenation reaction more effectively and that this is likely an effect of the liganddesign which must be considered when studying biomimetics. To gain more information on thestructures and impact of counterions of the complexes, we performed collision induced dissociation(CID) experiments and observe that the nitrates are more tightly bound than the triflates. To resolvethe structure of the complexes in the gas phase we combined DFT-calculations and ion mobilitymeasurements (IMS). Furthermore, we characterized the obtained complexes and reaction mixturesusing Electron Paramagnetic Resonance (EPR) spectroscopy and show the emergence of a quinone-based radical during the reaction with substrate and base.</div

Similar but Not the Same: First Kinetic and Structural Analyses of a Methanol Dehydrogenase Containing a Europium Ion in the Active Site

Contains fulltext : 193464.pdf (publisher's version ) (Open Access

Directed Zincation or Magnesiation of the 2‑Pyridone and 2,7‑Naphthyridone Scaffold Using TMP Bases

A regioselective zincation of the 2-pyridone and 2,7-naphthyridone scaffolds has been developed. Zincations of the methoxyethoxymethyl (MEM)-protected compounds using TMP₂Zn·2MgCl₂·2LiCl (TMP = 2,2,6,6-tetramethylpiperidyl) followed by trapping with electrophiles provided functionalized 2-pyridones and 2,7-naphthyridones. I/Mg exchange of iodinated 2-pyridone and 2,7-naphthyridone using <i>i-</i>PrMgCl·LiCl afforded magnesiated intermediates that reacted with electrophiles. A second magnesiation of the 2-pyridone scaffold was achieved by using TMPMgCl·LiCl. Additionally, we report CoCl₂-catalyzed cross-couplings of the 1-chloro-2,7-naphthyridines with arylzinc halides