Orotate complexes. Synthesis and crystal structure of lithium orotate(—I) monohydrate and magnesium bis[ orotate(—I)] octahydrate

Bach, I.; Kumberger, Otto; Schmidbaur, Hubert

doi:10.1002/cber.19901231207

Cited by 58 publications

(36 citation statements)

References 18 publications

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“…Chem. 13, 145-157 (1999) N(1) and COO À in R 2 SnHor (R = Me, Bu) (by analogy with literature reports); [5][6][7][8][9][10][11] (2) a monoanion in R 2 Sn(H 2 or) 2 , presumably with one of the two orotate units coordinating the tin atom through the carboxylate group and the other through the deprotonated nitrogen atom of an NH group; (3) a monoanion in R 3 SnH 2 or (R = Me, Bu) binding the organotin(IV) moieties only through COO À .…”

supporting

confidence: 61%

“…[5][6][7][8][9][10][11] However, in the case of the calcium(II) orotate system, the orotate behaves as a tridentate ligand in which, besides N(1), the carboxylato group chelates the metal through the two oxygen atoms. 8 Lithium(I) and magnesium(II) orotates were shown to contain monoanionic bidentate orotate groups, in which coordination occurred through one oxygen atom of the carboxylato group and one uracil oxygen atom.…”

Section: Introductionmentioning

confidence: 99%

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Organometallic complexes with biological molecules. X: dialkyltin(IV) and trialkyltin(IV) orotates: spectroscopic andin vivo investigations

Lencioni

Pellerito

Fiore

et al. 1999

Appl. Organometal. Chem.

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Several novel diorgano‐ and triorgano‐tin(IV) derivatives of orotic acid, (2,6‐dihydroxypyrimidine‐4‐carboxylic acid; H3or) have been synthesized. In the diorganotin(IV) derivatives, the orotic acid behaved either as a monoanionic or as a dianionic ligand, yielding R2Sn(H2or)2 and R2SnHor (R = Me, Bu) species, respectively, while in the triorganotin(IV) orotates only monodeprotonation of the orotic acid occurred, giving R3SnH2or (R = Me, Bu) derivatives. Structural hypotheses are proposed and discussed for the solid state based on Mössbauer and IR spectroscopic data, and for solution on 1H and 13C NMR results. Finally, investigations have been carried out in vivo, showing the inhibitor properties of all of the newly synthesized derivatives towards Ciona intestinalis embryos. In particular, in order to test the cytotoxicity in vivo of Me2SnHor, Bu2SnHor, Me3SnH2or and Bu3SnH2or, exposure to these chemicals of C. intestinalis embryos at the 2–4‐blastomere stage has been studied. The compound which exerts the highest cytotoxic effect is Bu3SnH2or at 10−5 M concentration because it blocks embryo development immediately. Me3SnH2or at 10−5 M concentration inhibits cell cleavage in the embryos at the 32‐blastomere stage, while Bu2SnHor at the same concentration gives rise to abnormal embryos. Me2SnHor, is less toxic than the trimethyl, dibutyl and tributyl analogues, since 40% of the total number of treated embryos resulted in normal larvae. The ligand does not affect embryonic development significantly. The results seem to indicate that the chemical species under investigation, especially Bu3SnH2or, interfere with polymerization of tubulin during the process of cell division in early embryo development. Copyright © 1999 John Wiley & Sons, Ltd.

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supporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Organometallic complexes with biological molecules. X: dialkyltin(IV) and trialkyltin(IV) orotates: spectroscopic andin vivo investigations

Lencioni

Pellerito

Fiore

et al. 1999

Appl. Organometal. Chem.

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“…To determine if a second coordination sphere of Mg 2+ without being connected to a first coordination sphere in proteins has been found previously, we looked into the literature, but did not find any Mg 2+ second coordination sphere caused by proteins in absence of a first sphere ion coordination [65,66]. However, crystal structures of small organic compounds, Mg-L-Asp [67], Mg(L-AspH)(D-AspH) [68] and Magnesium Bis[orotate(− I)] Octahydrata [69] have been shown to bind Mg 2+ ions in first or second coordination sphere, respectively. While in the first sphere of Mg-LAsp coordination the nitrogen lone pair coordinates the Mg 2+ ion (denoting that the backbone nitrogen is deprotonated and thus donating a favorable interaction to the Mg 2+ ion) the coordination in the first sphere complex from Mg(L-AspH)(D-AspH) the Mg 2+ ion is Although we found the second coordination sphere of the Mg 2+ ion in the above MD simulations of the ε subunit from B. subtilis, this could be due to a finite time of the simulation.…”

Section: The Mg 2+ Binding Site Derived By Conventional MD Simulationsmentioning

confidence: 80%

On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

Krah

Takada

2015

Biochimica et Biophysica Acta (BBA) - Bioenergetics

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F-type ATP synthases, central energy conversion machines of the cell synthesize adenosine triphosphate (ATP) using an electrochemical gradient across the membrane and, reversely, can also hydrolyze ATP to pump ions across the membrane, depending on cellular conditions such as ATP concentration. To prevent wasteful ATP hydrolysis, mammalian and bacterial ATP synthases possess different regulatory mechanisms. In bacteria, a low ATP concentration induces a conformational change in the ε subunit from the down- to up-states, which inhibits ATP hydrolysis. Moreover, the conformational change of the ε subunit depends on Mg(2+) concentration in some bacteria such as Bacillus subtilis, but not in others. This diversity makes the ε subunit a potential target for antibiotics. Here, performing molecular dynamics simulations, we identify the Mg(2+) binding site in the ε subunit from B. subtilis as E59 and E86. The free energy analysis shows that the first-sphere bi-dentate coordination of the Mg(2+) ion by the two glutamates is the most stable state. In comparison, we also clarify the reason for the absence of Mg(2+) dependency in the ε subunit from thermophilic Bacillus PS3, despite the high homology to that from B. subtilis. Sequence alignment suggests that this Mg(2+) binding motif is present in the ε subunits of some pathogenic bacteria. In addition we discuss strategies to stabilize an isolated ε subunit carrying the Mg(2+) binding motif by site directed mutagenesis, which also can be used to crystallize Mg(2+) dependent ε subunits in future.

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“…With the Cu(I) 25 and Zn(II) 26 cations, a bidentate coordination is observed whereas UO 2 (II) coordinates monodentately. 27 Compounds with the Zn(II) 28 and Mg(II) 29 cations, where the H 2 L − anion does not I. Kostova et al Bioorganometallic Chemistry enter the inner coordination sphere of the cation have also been reported.…”

Section: Introductionmentioning

confidence: 99%

New cerium(III) and neodymium(III) complexes as cytotoxic agents

Kostova

Rastogi

Kiefer

et al. 2006

Appl. Organometal. Chem.

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The cerium(III) and neodymium(III) complexes of 5-aminoorotic acid were synthesized and characterized by means of spectral data (IR, Raman, 1 H NMR and 13 C NMR) and elemental analysis. Significant differences in the IR spectra of the complexes were observed as compared with the spectrum of the ligand. A comparative analysis of the Raman spectra of the complexes with that of the free 5-aminoorotic acid allowed a straightforward assignment of the vibrations of the ligand groups involved in coordination. 1 H NMR and 13 C NMR spectra confirmed the formation of the complexes. The ligand and the complexes were tested for the cytotoxic activities on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein, and the non-Hodgkin lymphoma-derived DOHH-2, characterized by a rexpression of the antiapoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent manner, which enabled the construction of dose-response curves and the calculation of the corresponding IC 50 values. Cytotoxicity towards tumor cells was determined for a broad concentration range. The inorganic salts exerted a very weak cytotoxic effect on these cells that is in contrast to the lanthanide complexes, which exhibited potent cytotoxic activity towards K-562 and DOHH-2 cell lines.

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Orotate complexes. Synthesis and crystal structure of lithium orotate(—I) monohydrate and magnesium bis[ orotate(—I)] octahydrate

Cited by 58 publications

References 18 publications

Organometallic complexes with biological molecules. X: dialkyltin(IV) and trialkyltin(IV) orotates: spectroscopic andin vivo investigations

Organometallic complexes with biological molecules. X: dialkyltin(IV) and trialkyltin(IV) orotates: spectroscopic andin vivo investigations

On the Mg2+ binding site of the ε subunit from bacterial F-type ATP synthases

New cerium(III) and neodymium(III) complexes as cytotoxic agents

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