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López Leonardo, Carmen

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López Leonardo, Carmen
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Universidad de Murcia. Departamento de Química Orgánica
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    Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice
    (Wiley, 2021-03-16) Zapata- Pérez, Rubén; Tammaro, Alessandra; Schomakers, Bauke V.; Scantlebery, Angelique M. L.; Denis, Simone; Elfrink, Hyung L.; Giroud- Gerbetant, Judith; Cantó, Carles; López Leonardo, Carmen; McIntyre, Rebecca L.; Weeghel, Michel van; Sánchez Ferrer, Álvaro; Houtkooper, Riekelt H.; Química Orgánica; Bioquímica y Biología Molecular A; Facultad de Química; Facultad de Veterinaria
    Nicotinamide adenine dinucleotide (NAD+) homeostasis is constantly compromised due to degradation by NAD+-dependent enzymes. NAD+ replenishment by supplementation with the NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) can alleviate this imbalance. However, NMN and NR are limited by their mild effect on the cellular NAD+ pool and the need of high doses. Here, we report a synthesis method of a reduced form of NMN (NMNH), and identify this molecule as a new NAD+ precursor for the first time. We show that NMNH increases NAD+ levels to a much higher extent and faster than NMN or NR, and that it is metabolized through a different, NRK and NAMPT-independent, pathway. We also demonstrate that NMNH reduces damage and accelerates repair in renal tubular epithelial cells upon hypoxia/reoxygenation injury. Finally, we find that NMNH administration in mice causes a rapid and sustained NAD+ surge in whole blood, which is accompanied by increased NAD+ levels in liver, kidney, muscle, brain, brown adipose tissue, and heart, but not in white adipose tissue. Together, our data highlight NMNH as a new NAD+ precursor with therapeutic potential for acute kidney injury, confirm the existence of a novel pathway for the recycling of reduced NAD+ precursors and establish NMNH as a member of the new family of reduced NAD+ precursors.
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    Intramolecular cyclization of Azido-Isocyanides triggered by the Azide Anion: an experimental and computational study
    (American Chemical Society Publications, 2023-06-20) Alajarín Cerón, Mateo; Cutillas Font, Guillermo; López Leonardo, Carmen; Orenes, Raul-Angel; Marín Luna, Marta; Pastor Vivero, Aurelia; Química Orgánica
    This work describes the unprecedented intramolecular cyclization occurring in a set of alfa-azido-beta-isocyanides in the presence of catalytic amounts of sodium azide. These species yield the tricyclic cyanamides [1,2,3]triazolo[1,5-a]quinoxaline-5(4H)-carbonitriles, whereas in the presence of an excess of the same reagent, the azido-isocyanides convert into the respective C-substituted tetrazoles through a [3+2] cycloaddition between the cyano group of the intermediate cyanamides and the azide anion. The formation of tricyclic cyanamides has been examined by experimental and computational means. The computational study discloses the intermediacy of a long-lived N-cyanoamide anion, detected by NMR monitoring of the experiments, subsequently converting into the final cyanamide in the rate determining step. The chemical behavior of these azido-isocyanides endowed with an aryl-triazolyl linker, has been compared with that of a structurally identical azido-cyanide isomer, experiencing a conventional intramolecular [3+2] cycloaddition between its azido and cyanide functionalities. The synthetic procedures described herein constitute metal-free approaches to novel complex heterocyclic systems, such as [1,2,3]triazolo[1,5-a]quinoxalines and 9H-benzo[f]tetrazolo[1,5-d][1,2,3]triazolo[1,5-a][1,4]diazepines.
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    2-Isocyanoanilines and their mono-Boc-protected derivatives
    (Royal Society of Chemistry, 2025-07-15) Saura Sanmartín, Adrián; López Leonardo, Carmen; Alajarín Cerón, Mateo; Química Orgánica; Facultad de Química
    Among the variety of synthetically useful isocyanides, 2-isocyanoanilines have been scarcely reported in the chemical literature, despite the rich chemistry that expectedly could derive from the reactivities of their two functional groups. This is the case not only for the parent compound but also for most of their N-monosubstituted derivatives. The reason behind such behavior relies upon their chemical instability, apparently attributable to the presence of the N–H bond. Among these latter species, two tert-butyl carbamates are notorious exceptions, as they have been widely utilized in multicomponent reactions but poorly described. This review covers the chemistry of these compounds from a critical perspective, analyzing the causes of the instability of these privileged molecular scaffolds, as well as highlighting the reactivity of their mono-Boc-protected derivatives.
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