Synthesis and Structure of the Bis- and Tris-Polyhedral Hybrid Carboranoclathrochelates with Functionalizing Biorelevant Substituents-The Derivatives of Propargylamine Iron(II) Clathrochelates with Terminal Triple C≡C Bond(s).

Genrikh E Zelinskii,Anna V Vologzhanina,Yan Z Voloshin,Anton V Makarenkov,Valentina A Olshevskaya,Mikhail A Vershinin,Alexander S Chuprin,Semyon V Dudkin,Pavel V Dorovatovskii,Ilya P Limarev

doi:10.3390/molecules26123635

Abstract

A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed. In its first stage, a stepwise substitution of the dichloroclathrochelate precursor with amine N-nucleophiles of different natures in various solvents was performed. One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents. Further nucleophilic substitution of their remaining chlorine atoms with propargylamine in DMF led to morpholine- and diethylamine-functionalized monopropargylamine cage complexes, the molecules of which contain the single terminal C≡C bond. Their “click” 1,3-cycloaddition reactions in toluene with ortho-carborane-(1)-methylazide catalyzed by copper(II) acetate gave spacer-containing di- and tritopic iron(II) carboranoclatrochelates formed by a covalent linking between their different polyhedral(cage) fragments. The obtained complexes were characterized using elemental analysis, MALDI-TOF mass, UV-Vis, 1H, 1H{11B}, 11B, 11B{1H}, 19F{1H} and 13C{1H}-NMR spectra, and by a single crystal synchrotron X-ray diffraction experiment for the diethylamine-functionalized iron(II) carboranoclathrochelate. Its encapsulated iron(II) ion is situated almost in the center of the FeN6-coordination polyhedron possessing a geometry intermediate between a trigonal prism and a trigonal antiprism with a distortion angle φ of approximately 28°. Conformation of this hybrid molecule is strongly affected by its intramolecular dihydrogen bonding: a flexibility of the carborane-terminated ribbed substituent allowed the formation of numerous C–H…H–B intramolecular interactions. The H(C) atom of this carborane core also forms the intermolecular C–H…F–B interaction with an adjacent carboranoclathrochelate molecule. The N–H…N intermolecular interaction between the diethylamine group of one hybrid molecule and the heterocyclic five-membered 1H-[1,2,3]-triazolyl fragment of the second molecule of this type caused formation of H-bonded carboranoclathrochelate dimers in the X-rayed crystal.

Highlights

Among the earlier-described d-metal monomacrobicyclic complexesand their bis-cage analogs, shown in Scheme 1 with terminal biorelevant, first of all, carboxyl group(s), compounds 1–5 are reported to be the most prospective bioeffectors, including the so-called “topological drugs” [2,3] and molecular optical probes [4,5,6]
A synthetic strategy for obtaining structurally flexible hybrid iron(II) carboranoclatrochelates functionalized with biorelevant groups, based on a combination of a 1,3-dipolar cycloaddition reaction with nucleophilic substitution of an appropriate chloroclathrochelate precursor, was developed
One of its two chlorine atoms with morpholine or diethylamine in dichloromethane gave reactive monohalogenoclathrochelate complexes functionalized with abiorelevant substituents

Summary

Introduction

Among the earlier-described d-metal monomacrobicyclic complexes (clathrochelates [1,2]). It is clear that such a mechanism of cytotoxic activity of cage complexes with an encapsulated metal ion is substantially less probable in the case of metal clathrochelates, the molecules of which do not contain the highly reactive terminal group(s) or atom(s), first of all, the halogen atom(s) as the ribbed substituent(s) in a macrobicyclic framework. These functionalizing substituents in the chelate fragment(s) of highly π-conjugated polyazomethine encapsulating ligands are known [1,2]. The most effective and convenient pathway of a ribbed functionalization of these complexes is based on nucleophilic substitution of their appropriate reactive halogenoclathrochelate precursors with various N, O, S, C-nucleophilic agents [2]

B OO O N N N NH

Results and Discussion

B ON O N ON

Synthesis

X-ray Crystallography

Conclusions