Post-Synthetic Modification Research of Salan Titanium bis-Chelates via Sonogashira Reaction

doi:10.6023/A21060282

	Post-Synthetic Modification Research of Salan Titanium bis-Chelates via Sonogashira Reaction
	Zhao, Tiankun; Wang, Peng; Ji, Mingyu; Li, Shanjia; Yang, Mingjun; Pu, Xiuying
刊名	ACTA CHIMICA SINICA
	2021-11-15
卷号	79 期号:11 页码:1385-1393
关键词	Sonogashira reaction [SalanTi((IV)) Dipic] complexes antitumor activity alkyne functionalization aqueous
ISSN号	0567-7351
DOI	10.6023/A21060282
英文摘要	A palladium-catalyzed Sonogashira reaction has been developed for the highly efficient post-modification of ONNO Salan ligand and 2,6-dipicolinic acid stabilized titanium bis-chelates with anticancer activity. Different alkynyl substituents were introduced to Salan and 2,6-dipicolinic acid, respectively. In total 20 novel titanium complexes containing mono-, di- and tri-alkynyl substituents as well as a complex containing tumor targeting ethinylestradiol were synthesized, all complexes were characterized by 1H NMR and C-13 NMR, HRMS, UV-vis and IR spectroscopy. The nature of obtained titanium complexes that losing solvent molecules fast when exposed to air makes it hard to obtain satisfactory single crystals for X-ray diffraction measurement. Most alkynyl titanium complexes exhibit enhanced inhibitory activity against HeLa S3 and Hep G2 tumor cells in the micromole range. The introduction of alkynyl group to the Salan demonstrated less significant contribution to the anti-tumoral activity. However, the anti-tumoral activity alters with different alkynyl substituents on the 2,6-dipicolinic acid. Of all complexes, 3j [Salan(2,4-dimethyl)Ti(IV) Dipic(4-(3-(dimethylamino)-prop-1-yn-1-yl))] showed excellent inhibitory activity, its IC50 value is an order of magnitude higher than that of Cisplatin, which is the most active anti-tumoral Salan titanium compound in this study [3j, HeLa S3: IC50=(0.5 +/- 0.1) mu mol/L, Hep G2: IC50=(0.7 +/- 0.2) mu mol/L; Cisplatin, HeLa S3: IC50=(3.3 +/- 0.2) mu mol/L, Hep G2: IC50=(6.0 +/- 1.1) mu mol/L]. In general, aromatic alkynyl substitution containing electron withdrawing moiety proved to have a positive influence on complex's anti-tumoral activity than those containing electron donating moiety. Short chain aliphatic alkynyl substituents benefit the complex's inhibitory activity. However, increased aliphatic chain length results in fast loss of complexes' activity. Stability study on the representative aromatic alkynyl 2a, 3a and aliphatic alkynyl 2f, 3j suggests that the alkynyl's electron nature can alter the complex stability. 2a and 2f, with substitutions on the Salan (2 position non-substituted), their half hydrolyzation time (t1/2) are 5 and 10 h, respectively. The hydrolysate of 2a was characterized to be the non-toxic alkynyl Salan ligand 1a*. For 3a and 3j, the 2 position of Salan are occupied by methyl groups, their protective effect to the titanium center resulted in a stable behavior of both in the presence of an aqueous media. In addition, the structure-activity relationship and development prospects of these novel alkynyl Salan titanium bis-chelates are summarized and prospected.
WOS研究方向	Chemistry
语种	中文
出版者	SCIENCE PRESS
WOS记录号	WOS:000716442000008
内容类型	期刊论文
源URL	[http://ir.lut.edu.cn/handle/2XXMBERH/150044]
专题	生命科学与工程学院
作者单位	Lanzhou Univ Technol, Coll Life Sci & Engn, Lanzhou 730050, Peoples R China
推荐引用方式 GB/T 7714	Zhao, Tiankun,Wang, Peng,Ji, Mingyu,et al. Post-Synthetic Modification Research of Salan Titanium bis-Chelates via Sonogashira Reaction[J]. ACTA CHIMICA SINICA,2021,79(11):1385-1393.
APA	Zhao, Tiankun,Wang, Peng,Ji, Mingyu,Li, Shanjia,Yang, Mingjun,&Pu, Xiuying.(2021).Post-Synthetic Modification Research of Salan Titanium bis-Chelates via Sonogashira Reaction.ACTA CHIMICA SINICA,79(11),1385-1393.
MLA	Zhao, Tiankun,et al."Post-Synthetic Modification Research of Salan Titanium bis-Chelates via Sonogashira Reaction".ACTA CHIMICA SINICA 79.11(2021):1385-1393.