DFT and X-Ray Structural Studies of N(7)-Tetramethylbenzyl/Pentamethylbenzyl Theophylline Derivatives and Their Catalytic Applications

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Demir Düşünceli S., Kaloğlu N., Üstün E., Şahin O.

CHEMISTRYSELECT, cilt.33, sa.11, ss.1-10, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 33 Sayı: 11
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1002/slct.74292
  • Dergi Adı: CHEMISTRYSELECT
  • Derginin Tarandığı İndeksler: Academic Search Ultimate (EBSCO), Scopus, Science Citation Index Expanded (SCI-EXPANDED), Chemical Abstracts Core
  • Sayfa Sayıları: ss.1-10
  • Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
  • İnönü Üniversitesi Adresli: Evet

Özet

Theophylline, a naturally occurring xanthine derivative with well-established pharmaceutical applications, has recently emergedas an attractive scaffold in coordination chemistry and catalysis because of its unique heterocyclic structure and donorproperties. In this study, two novel N(7)-substituted theophylline derivatives, namely 1,3-dimethyl-7-((2,3,5,6-tetramethyl)benzyl)-3,7-dihydro-1H-purine-2,6-dione and 1,3-dimethyl-7-((2,3,4,5,6-pentamethyl)benzyl)-3,7-dihydro-1H-purine-2,6-dione, were syn-thesized and comprehensively characterized by spectroscopic methods, single-crystal x-ray diffraction analysis, and densityfunctional theory (DFT) calculations. Structural and theoretical investigations were carried out to evaluate their electronicfeatures, coordination behavior, and potential interaction sites. For the first time, these theophylline-based heterocycliccompounds were employed as ligand-like components in in situ generated palladium catalytic systems for C─H bond activationreactions. The catalytic results demonstrated that the N(7)-substituted theophylline framework effectively stabilizes palladiumintermediates and promotes selective C─H functionalization under mild reaction conditions. DFT studies further revealed thatthe nitrogen donor centers of the theophylline scaffold play an important role in tuning the electronic properties and reactivityof the palladium species. In addition, frontier molecular orbital analyses, including HOMO–LUMO energy levels and orbitallocalizations, provided insight into the possible coordination and interaction regions of the molecules. These findings establishN(7)-substituted theophylline derivatives as a new class of ligand-like scaffolds for Pd-catalyzed C─H activation.