Banca de QUALIFICAÇÃO: MATEUS MARTINS ZANOTTO DE TOLEDO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : MATEUS MARTINS ZANOTTO DE TOLEDO
DATE: 27/08/2025
TIME: 14:00
LOCAL: https://conferenciaweb.rnp.br/webconf/paula-38
TITLE:

Exploring Novel Xanthenes as Targeted Photosensitizers: Substituent Design, pH Modulation, and Membrane Affinity for Enhanced Photodynamic Therapy

PAGES: 25
BIG AREA: Ciências Exatas e da Terra
AREA: Química
SUBÁREA: Físico-Química
SPECIALTY: Química Teórica
SUMMARY:

This study introduces four novel xanthenes, computationally designed as selective probes and photosensitizing agents for cancer cell uptake. pKa analyses revealed that monoanionic species dominate at pH 6.0, increasing membrane affinity in acidic environments. DFT and DLPNO-CCSD calculations, as well as molecular dynamics
simulations, were performed for the four compounds (XA2, XA4, XA6, and XABr) in their mono and dianionic forms. Key findings emphasize the importance of substituent design in balancing charge and flexibility, aiming to enhance intersystem crossing (ISC) efficiency for advanced photosensitizers. Notably, natural transition orbital (NTO) analysis revealed XA6’s pronounced charge-separated states. XABr-2 and XA2-1 also exhibited similar, albeit less prominent, charge separation. XABr-2 xanthene-localized donor orbitals complement delocalized acceptor orbitals, while XA6-2 acceptor orbitals align with substituents. Spin-Orbit Coupling Matrix Elements (SOCME) show a higher coupling, thus higher ISC, for the monoionic than dianionic XA2, XA4, and XA6. Moreover, molecular dynamics simulations revealed substituent-dependent interactions with membranes, highlighting the superior uptake of monoanions due to their reduced charge. XA4 flexible substituents exhibited unexpected
dianion-membrane interactions. Specifically, brominated helicene (XABr) and extended aromatic systems (XA6), which were localized near oxidation-prone double bonds, a primary target in photodynamic therapy.

COMMITTEE MEMBERS:
Presidente - Interno ao Programa - 1544394 - PAULA HOMEM DE MELLO
Membro Titular - Examinador(a) Externo à Instituição - ELIZETE VENTURA DO MONTE - UFPB
Membro Titular - Examinador(a) Externo à Instituição - MAURICIO DA SILVA BAPTISTA - USP
Membro Suplente - Examinador(a) Interno ao Programa - 1544403 - MAURICIO DOMINGUES COUTINHO NETO