Phosphorus-Nitrogen Compounds. Part 85. Design and Synthesis of Novel Hybrid Multiheterocyclic spiro- and 2-cis-4-ansa-Ferrocenyl-(N/O)-cyclotetraphosphazene Conjugates Bearing Piperonal Pendant Arms: Structural Characterizations, Carbonic Anhydrase Activation, and Antioxidant Activity Studies
Applied Organometallic Chemistry, cilt.40, sa.6, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 40 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.1002/aoc.70595
- Dergi Adı: Applied Organometallic Chemistry
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, Chimica, Compendex, DIALNET, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Anahtar Kelimeler: antioxidant activity, carbonic anhydrase activity, crystallography, cyclotetraphosphazenes, spectroscopy
- Hacettepe Üniversitesi Adresli: Evet
Özet
The reaction of octachlorocyclotetraphosphazene, N4P4Cl8, OCCP-(1), with sodium-3-(N-ferrocenylmethylamino)-1-propanoxide-(L1) in an equimolar ratio of 1:1 led to the formation of the starting compounds, mono-ferrocenyl-spiro-(spiro-2) and 2-cis-4-dichloro-ansa-(ansa-3) (N/O)cyclotetraphosphazenes. The piperonal pendant armed cyclotetraphosphazenes were prepared from the reactions of spiro-2 and ansa-3 with bidentate ligands, N-(piperonalyl)-N′-methyl-1,3-diamino-propane-(L2) and sodium-3-(piperonalylamino)-1-propanoxide-(L3). Spiro-2 was separately reacted with L2 and L3 to afford trispiro-2a (ctt-2a and tct-2a; c:cis and t:trans) and tetraspiro-2a (cctt-2a and tctc-2a), and tetraspiro-2b (cctt-2b) cyclotetraphosphazenes, respectively. However, the reactions of ansa-3 with excess L2 and L3 resulted in the formation of ansa-dispiro-3a (ctt-3a) and ansa-dispiro-3b (ctt-3b) cyclotetraphosphazenes, respectively. These novel products were synthesized to investigate their spectroscopic, stereogenic, crystallographic and bioactivity properties. The structures of piperonalyl-cyclotetraphosphazenes were evaluated by elemental analysis, ESI-MS, FTIR, 1H, 13C{1H} and 31P{1H} NMR techniques. The compounds had two (ansa-3, cctt-2a/tctc-2a and cctt-2b), three (ctt-2a) and four (ctt-3a and ctt-3b) stereogenic P-centers. The molecular and crystal structures of ctt-3a were confirmed by X-ray crystallography and its Hirshfeld surface (HS) analysis was performed. Thus, the crystal structure of ctt-3a revealed the absolute configuration of one enantiomer (RS'R′S″). Carbonic anhydrase activator and antioxidant activities of the cyclotetraphosphazenes were evaluated. Based on the in vitro activator effects of these compounds on the esterase activities of hCA I and hCA II isoenzymes, trispiro-2a was found to have the strongest activator (KA = 17.53 ± 2.63 μM). Additionally, among the derivatives evaluated, trispiro-2a (91.3% ± 0.2%) and tetraspiro-2b (89.3% ± 0.1%) demonstrated exceptionally high free radical scavenging (antioxidant) activities (FRSAs), approaching those of standard antioxidants (BHA 94.0% ± 0.3% and α-tocopherol 97.1% ± 0.1%).