Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies

Mono- and bis-decylated lumazines have been synthesized and characterized. Namely, mono-decyl chain [1-decylpteridine-2,4(1,3H)-dione] 6a and bis-decyl chain [1,3-didecylpteridine-2,4(1,3H)-dione] 7a conjugates were synthesized by nucleophilic substitution (SN 2) reactions of lumazine with 1-iododec...

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Autores principales: Sosa, María José, Urrutia, María Noel, Schilardi, Patricia Laura, Quindt, Matías Iván, Bonesi, Sergio M., Denburg, Dobrushe, Vignoni, Mariana, Greer, Alexander, Greer, Edyta M., Thomas, Andrés Héctor
Formato: Articulo Preprint
Lenguaje:Inglés
Publicado: 2020
Materias:
Química
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/146507
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-146507
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Química
spellingShingle Química
Sosa, María José
Urrutia, María Noel
Schilardi, Patricia Laura
Quindt, Matías Iván
Bonesi, Sergio M.
Denburg, Dobrushe
Vignoni, Mariana
Greer, Alexander
Greer, Edyta M.
Thomas, Andrés Héctor
Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
topic_facet Química
description Mono- and bis-decylated lumazines have been synthesized and characterized. Namely, mono-decyl chain [1-decylpteridine-2,4(1,3H)-dione] 6a and bis-decyl chain [1,3-didecylpteridine-2,4(1,3H)-dione] 7a conjugates were synthesized by nucleophilic substitution (SN 2) reactions of lumazine with 1-iododecane in N,N-dimethylformamide (DMF) solvent. Decyl chain coupling occurred at the N1 site and then the N3 site in a sequential manner, without DMF condensation. Molecular orbital (MO) calculations show a p-orbital at N1 but not N3 , which along with a nucleophilicity parameter (N) analysis predict alkylation at N1 in lumazine. Only after the alkylation at N1 in 6a, does a p-orbital on N3 emerge thereby reacting with a second equivalent of 1-iododecane to reach the dialkylated product 7a. Data from NMR (1 H, 13 C, HSQC, HMBC), HPLC, TLC, UV-vis, fluorescence and density functional theory (DFT) provide evidence for the existence of mono-decyl chain 6a and bis-decyl chain 7a. These results differ to pterin O-alkylations (kinetic control), where N-alkylation of lumazine is preferred and then to dialkylation (thermodynamic control), with an avoidance of DMF solvent condensation. These findings add to the list of alkylation strategies for increasing sensitizer lipophilicity for use in photodynamic therapy.
format Articulo
Preprint
author Sosa, María José
Urrutia, María Noel
Schilardi, Patricia Laura
Quindt, Matías Iván
Bonesi, Sergio M.
Denburg, Dobrushe
Vignoni, Mariana
Greer, Alexander
Greer, Edyta M.
Thomas, Andrés Héctor
author_facet Sosa, María José
Urrutia, María Noel
Schilardi, Patricia Laura
Quindt, Matías Iván
Bonesi, Sergio M.
Denburg, Dobrushe
Vignoni, Mariana
Greer, Alexander
Greer, Edyta M.
Thomas, Andrés Héctor
author_sort Sosa, María José
title Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
title_short Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
title_full Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
title_fullStr Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
title_full_unstemmed Mono- and Bis-Alkylated Lumazine Sensitizers: Synthetic, Molecular Orbital Theory, Nucleophilic Index and Photochemical Studies
title_sort mono- and bis-alkylated lumazine sensitizers: synthetic, molecular orbital theory, nucleophilic index and photochemical studies
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/146507
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