Syntheses And Applications Of Pnictogen-Containing Functional Compounds Based On Metal Coordination Bonds

Pnictogens with ns²np³ valence electron configurations have drawn considerable attention because they can easily coordinate with metal or non-metal atoms.In the past decades,there are progresses on the synthesis of pnictogen-containing organic compounds based on metal coordination.Meanwhile,a number of nitrogen-,antimony-,bismuth-containing organic compounds have been applied in fields of organic synthesis,catalysis,pharmacy and material science.Despite the advances,there are problems to tackle.For instances:（1）The mismatch of center atom and ligand would result in compound instability and application restriction;（2）a number of methodologies for the construction of metal coordination bonds have shortcomings such as harsh conditions,poor atomic economy,and environmental pollution;（3）there are relatively few thermodynamics and kinetics studies on the formation of metal coordination bonds,and theoretical guidance for clever design of complexes is lacking;（4）researches on the correlations between structures and properties of complexes are rare,leading to aimless preparation of non-functional metal complexes.It is hence of significance to develop green and efficient methodologies for the construction of metal coordination bonds in a rational manner.In the present work,a series of nitrogen-,antimony-,bismuth-containing organic compounds were synthesized by means of stable metal-ligand coordination.The composition,structure and bonding processes were characterized by NMR,single crystal X-ray diffraction,elemental analysis,X-ray photoelectron spectroscopy and density functional theory calculations.Furthermore,their applications in the field of organic synthesis,Lewis acid catalysis and antitumor performance as well as the related mechanism and structure-activity relationship were systematically investigated.The innovative results and conclusions are summarized as follows:1.The coordination-induced oxidative C（sp³）-H/N-H cross-coupling of P（O）NH compounds with hydrocarbons using copper acetate as catalyst has been described.The kinetic,mechanistic and DFT calculation studies reveal that,the coproduct acetic acid acts as an additive to promote the formation of the intermediate bis（（diphenylphosphoryl）（quinolin-8-yl）amino）copper,and consequently there is the acceleration of C（sp³）-N bond construction.The reaction proceeds efficiently with a wide array of hydrocarbons and P（O）NH compounds,and the role of acetic acid in the rate acceleration has been repeatedly proven.Furthermore,the efficiency of small-scale reaction could be retained upon gram-scale synthesis in a continuous manner.2.A protocol for coordination-assisted oxidative C（sp²）–N cross-coupling of P（O）NH compounds and aryl boronic acids over copper powder under oxygen atmosphere has been reported.The reaction proceeds efficiently to afford N,N-disubstituted phosphonamides at room temperature in excellent yields without the use of any external ligands or acid/base additives.The protocol works efficiently with a diversity of P（O）NH compounds and aryl boronic acids that are structurally and electronically different.The control experiments confirmed that the reaction does not involve any free radicals,but 8-amidoquinoline or 2-aminooxazoline coordination is critical.Finally,the results of mechanistic studies demonstrate that the copper species undergoes Cu（0）→Cu（I）→Cu（II）transformation,and the copper（II）species is the stable state of this reaction.3.A series of organoantimony（III）halide complexes with tetrahydrodibenzo[c,f][1,5]azastibocine framework were synthesized and employed as water-tolerant Lewis acid catalysts.In the systematic studies of structure-activity relationship,it was disclosed that the strength of N→Sb donor-acceptor interaction could be synergistically modulated by tuning the property of nitrogen substituents and halogen atoms adjacent to the central antimony atom.As a consequence,the complexes display distinct catalytic performance towards Mannich,cross-condensation,cyclization-aromatization and epoxides aminolysis reaction.The fluorinated organoantimony（III）derivatives were found to be more active than the chlorinated,brominated and iodinated analogues,owing to the role of Sb–F moiety as hydrogen bond acceptor.By comparison,the compound CyN（C₆H₄CH₂）₂SbF（Sb4）is the highest in catalytic activity.In addition,Sb4 also shows facile reusability in scale-enlarged synthesis.4.The relationship between chemical structure and in vitro cytotoxic activities of a series of azastibocine-framework organoantimony（III）halide complexes in growth inhibition of cancerous（HepG2,MDA-MB-231,MCF-7 and HeLa）and nonmalignant（HEK-293）cell lines was studied for the first time.A positive correlation between cytotoxic activity and the length of N→Sb coordinate bond on the azastibocine framework of same nitrogen substituent was observed.By comparison,the organoantimony（III）fluoride Sb4 exhibits the highest selectivity index,giving a IC₅₀（nonmalignant）/IC₅₀（cancerous）ratio of up to 8.33.The results of cell cycle analysis indicate that the inhibitory effect of Sb4 on cellular viability is caused by cell cycle arrest mainly at the S phase.The necrosis induced by Sb4 was confirmed by the Trypan blue dye exclusion test as well as evidenced by the increase of lactic dehydrogenase released in the culture medium.Furthermore,by quantifying the relative fluorescence units using a spectrofluorometer,the levels of intracellular reactive oxygen species（ROS）in cancerous cells were evaluated,and the results indicate that the cytotoxic activity of Sb4 is ROS dependent.5.A series of heterocyclic organobismuth（III）complexes containing intramolecular E→Bi coordinate bonds were synthesized and evaluated for growth inhibition of cancerous（A549,SMCC7721,SGC-7901 and SGC-7901）and nonmalignant（16HBE14o-）cell lines using the CCK-8 method.It was found that the compound O（C₆H₄CH₂）₂BiONO₂（Bi2）exhibits potent cytotoxic activities against selected cancer cell lines together with intriguing biological selectivity.The results of morphological changes and flow cytometry indicate that Bi2 can induce apoptosis in a time-dependent and dose-dependent manner,thereby inhibiting the growth of tumor cells.Furthermore,the outcomes of quantitative real-time PCR and Western blot analyses demonstrate that the apoptosis is a result of caspase-3 activation as well as up-regulation of Bcl-2/Bax level.