Issue 36, 2025

Phosphorus–nitrogen compounds. Part 80. Design and synthesis of hybrid multiheterocyclic cyclotriphosphazene conjugates bearing unsymmetrical pendant arms: spectral and crystallographic characterization, bioactivity and structure–activity relationship (SAR) studies

Abstract

Hexachlorocyclotriphosphazene, N3P3CI6 (HCCP), serves as the main inorganic template to produce organocyclotriphosphazenes. Herein, initially, diamines (1–6) were synthesized, which were used as ligands to obtain tetrachlorospirocyclotriphosphazenes (1a–6a). Geminal dichloro (7–9) and fully substituted (10–13) N-ferrocenyl-N′-(4-chlorobenzyl)spiro-(NN)-cyclotriphosphazenes were obtained from the reactions of tetrachlorophosphazenes (5a and 6a) with pyrrolidine and 1,4-dioxa-8-aza-spiro [4,5]decane (DASD). Geminal phosphazenes (7–9) have “chiral P atoms”. The 31P-spectrum of 9 with the addition of chiral solvating agent (CSA), (R)-(−)-2,2,2-trifluoro-1-(9-anthryl)ethanol, proved that this compound exists as a “racemate.” The structural characterizations of the new phosphazenes were carried out using 1D NMR (1H, 13C, 31P) and LC-MS techniques. Single-crystal X-ray crystallography revealed the molecular and crystal structures of tetrachloro (5a and 6a) and tetra-pyrrolidino (10) cyclotriphosphazenes. Moreover, the highest free radical scavenging activities (FRSAs, %) were observed for 8 (21.8 ± 0.6). In addition, interactions with DNA and enzyme digestions were investigated. Also, the antibacterial and antifungal activities of all compounds were evaluated and compared with various cyclotriphosphazenes containing ferrocenyl/4-chlorobenzyl pendant arms for the structure–activity relationship (SAR) using MIC, MBC and MFC values. Dichlorophosphazene 8 (MIC = 9.8 μM) is very effective against B. cereus, B. subtilis, S. aureus, E. faecalis and E. hirae bacteria. However, fully-substituted phosphazene 10 (MIC = 9.8 μM) exhibits potent antifungal activity against C. albicans and C. krusei. These distinctions highlight their potential for specific bacterial and fungal threats.

Graphical abstract: Phosphorus–nitrogen compounds. Part 80. Design and synthesis of hybrid multiheterocyclic cyclotriphosphazene conjugates bearing unsymmetrical pendant arms: spectral and crystallographic characterization, bioactivity and structure–activity relationship (SAR) studies

Supplementary files

Article information

Article type
Paper
Submitted
13 Jun 2025
Accepted
10 Aug 2025
First published
13 Aug 2025

New J. Chem., 2025,49, 15866-15884

Phosphorus–nitrogen compounds. Part 80. Design and synthesis of hybrid multiheterocyclic cyclotriphosphazene conjugates bearing unsymmetrical pendant arms: spectral and crystallographic characterization, bioactivity and structure–activity relationship (SAR) studies

R. Cemaloğlu, N. Uzunalioğlu, H. Akbaş, N. Asmafiliz, Z. Kılıç, B. N. Sabah, L. Açık and T. Hökelek, New J. Chem., 2025, 49, 15866 DOI: 10.1039/D5NJ02457A

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