Zugang zu metallorganischen Arylcobaltcorrinen durch radikalische Synthese: 4‐Ethylphenylcobalamin, ein potenzielles “Antivitamin B<sub>12</sub>”

Diamagnetic chemical exchange saturation transfer (CEST) contrast agents offer an alternative to Gd3+-based contrast agents for MRI. They are characterized by containing protons that can rapidly exchange with water and it is advantageous to have these protons resonate in a spectral window that is far removed from water. Here, we report the first results of DFT calculations of the 1H nuclear magnetic shieldings in 41 CEST agents, finding that the experimental shifts can be well predicted (R2 = 0.882). We tested a subset of compounds with the best MRI properties for toxicity and for activity as uncouplers, then obtained mice kidney CEST MRI images for three of the most promising leads finding 16 (2,4-dihydroxybenzoic acid) to be one of the most promising CEST MRI contrast agents to date. Overall, the results are of interest since they show that 1H NMR shifts for CEST agents—charged species—can be well predicted, and that several leads have low toxicity and yield good in vivo MR images.

Section: Porphyrineunclassified

Chemical Exchange Saturation Transfer (CEST) Agents: Quantum Chemistry and MRI

Feng

Zhu

et al. 2015

“…[18,20] But in contrast to TC, the B 12 -binding proteins hIF and hHC (rhHC) are glyco-proteins. [21] Artificial, covalent B 12 complexes with diagnostic or potentially therapeutic cargoes have functioned as vehicles for B 12 uptake and transport through the endogenous system, and related B 12 carriers with a toxic load have found use as molecular "Trojan horses". Indeed, the three B 12 binders have all been shown to bind to a variety of Cbl derivatives, carrying different upper axial ligands at the Co atom, including coenzyme B 12 [20] and non-natural organometallic cobalamins.…”

mentioning

confidence: 99%

“…Indeed, the three B 12 binders have all been shown to bind to a variety of Cbl derivatives, carrying different upper axial ligands at the Co atom, including coenzyme B 12 [20] and non-natural organometallic cobalamins. [21] Artificial, covalent B 12 complexes with diagnostic or potentially therapeutic cargoes have functioned as vehicles for B 12 uptake and transport through the endogenous system, and related B 12 carriers with a toxic load have found use as molecular "Trojan horses". [10a] Likewise, in the new organometallic B 12 -DNA conjugate Co-(dN) 18 -Cbl (1), the B 12 moiety represents a potential vector for transferring single stranded DNA into human cells.…”

mentioning

confidence: 99%

“…Further studies may help clarify, whether such a protein glycosidation is a competing motif for interaction with the DNA moiety of the octadecanucleotide 1 . Indeed, the three B 12 binders have all been shown to bind to a variety of Cbl derivatives, carrying different upper axial ligands at the Co atom, including coenzyme B 12 20 and non‐natural organometallic cobalamins 21…”

mentioning

confidence: 99%

See 1 more Smart Citation

Organometallic B₁₂–DNA Conjugate: Synthesis, Structure Analysis, and Studies of Binding to Human B₁₂‐Transporter Proteins

Hunger

Mutti

Rieder

et al. 2014

Self Cite

Design, synthesis, and structural characterization of a B12-octadecanucleotide are presented herein, a new organometallic B12-DNA conjugate. In such covalent conjugates, the natural B12 moiety may be a versatile vector for controlled in vivo delivery of oligonucleotides to cellular targets in humans and animals, through the endogenous B12 transport systems. Binding of the organometallic B12 octadecanucleotide to the three important human proteins of B12 transport was studied, to examine its structural suitability for the task of eventual in vivo oligonucleotide delivery. Binding was efficient with transcobalamin (TC), but not so efficient with the homologous glycoproteins intrinsic factor and haptocorrin. Binding of the B12 octadecanucleotide to TC suggests the capacity of the B12 moiety to serve as a natural vector for specific transport of single stranded, organometallic oligonucleotide loads from the blood stream into cells.

“…9 Metallorganische Arylcobalamine weichen von dieser Regel zum Teil ab und weisen Thermolyse‐beständige Co‐C

_{sp^{2}}

‐Bindungen auf. Sie repräsentieren eine neue Linie konzipierter B 12 ‐Antimetaboliten und sind potenzielle Antivitamine B 12 10. In diesem Zusammenhang können auch metallorganische Alkinyl‐B 12 ‐Derivate mit einer Co‐C sp ‐Bindung von besonderem Interesse sein.…”

Section: Methodsunclassified

A Versatile Approach to CF₃‐Containing 2‐Pyrrolidones by Tandem Michael Addition–Cyclization: Exemplification in the Synthesis of Amidine Class BACE1 Inhibitors

Mateu

Ciordia

Delgado

et al. 2015