酰腙及其金属配合物表现出良好的抗癌、抗病毒、抗微生物、抗炎和抗氧化等生物活性，引起了广泛关注。本文设计合成了3种单吡啶酰腙化合物和1种双吡啶酰腙化合物及其3种双吡啶四核过渡金属配合物，并研究了它们与小牛胸腺DNA(CT-DNA)和牛血清白蛋白(BSA)之间的相互作用以及体外抑菌活性。

本文主要工作如下：

(1) 单/双吡啶酰腙及其金属配合物的合成

合成了3种单吡啶酰腙化合物，分别为4-氯-苯甲醛-4-氯-吡啶-2-甲酰腙(C₁₃H₉Cl₂N₃O, L₁)，4-溴-苯甲醛-4-氯-吡啶-2-甲酰腙(C₁₃H₉BrClN₃O, L₂)和4-碘-苯甲醛-4-氯-吡啶-2-甲酰腙(C₁₃H₉ClIN₃O, L₃)，以及1种双吡啶酰腙化合物及其3种金属配合物，分别为2-乙酰基吡啶-4-氯-2-吡啶甲酰腙(C₁₃H₁₁ClN₄O, L₄)及其Cu配合物{C₅₂H₄₀Cl₄Cu₄N₂₀O₁₆, [Cu₄(NO₃)₂(dp-L₄)₄](NO₃)₂, C₁}、Co配合物{C₅₄H₄₈Cl₄Co₄N₂₀O₁₈, [Co₄(NO₃)₂(H₂O)(C₂H₅OH)(dp-L₄)₄](NO₃)₂, C₂}和Zn配合物{C₅₄H₄₈Cl₄N₂₀O₁₈Zn₄, [Zn₄(NO₃)₂(H₂O)(C₂H₅OH)(dp-L₄)₄](NO₃)₂, C₃}，并培养了它们的单晶。

(2) 单/双吡啶酰腙及其金属配合物的表征

利用元素分析、红外光谱、核磁氢谱和X-射线单晶衍射分析对L₁、L₂、L₃、L₄、C₁、C₂和C₃的结构进行了表征。X-射线单晶衍射表明L₁、L₂、L₃和L₄的晶体均属于单斜晶系，L₁、L₂和L₃属于Cc空间群，L₄属于P2₁/c空间群，它们均以酮式结构存在；C₁、C₂和C₃的晶体属于三斜晶系，P-1空间群，配体dp-L₄均以去质子化的烯醇式结构存在。另外，C₁、C₂和C₃均为四核配合物。

(3) 单/双吡啶酰腙及其金属配合物与CT-DNA的相互作用研究

L₁、L₂和L₃与CT-DNA均以沟槽方式与CT-DNA结合，结合过程为自发过程，结合亲和力的大小顺序为：L₃ > L₂ > L₁。L₁、L₂和L₃与DNA的分子间相互作用包括了氢键作用和疏水作用。

C₁、C₂和C₃以嵌插方式与CT-DNA结合，而L₄则以沟槽方式与CT-DNA结合，结合亲和力的大小顺序为：C₁ > C₂ > C₃ > L₄。结合过程均为自发熵增的吸热过程。L₄与DNA的分子间相互作用包括了氢键作用和疏水作用，C₁、C₂和C₃与DNA的分子间相互作用包括了氢键作用、疏水作用和静电作用。

(4) 单/双吡啶酰腙及其金属配合物与BSA的相互作用研究

L₁、L₂和L₃均可与BSA有效结合，结合亲和力的大小顺序为：L₃ > L₂ > L₁。L₁、L₂和L₃在BSA中的唯一结合位点均位于TRP213残基附近的疏水空腔中，分子间相互作用包括了氢键作用、卤键作用和疏水作用。分子对接结果表明，TRP213残基参与了L₁、L₂和L₃与BSA之间的疏水作用，这是BSA荧光猝灭的主要原因。另外，碘-氧卤键作用比氯-氧、溴-氧卤键作用要强。

L₄、C₁、C₂和C₃与BSA结合亲和力的大小顺序为：C₁ > C₃ > C₂ > L₄。结合过程均为自发熵增的吸热过程。L₄在BSA中的唯一结合位点位于TRP213残基附近的疏水空腔中，它们之间的相互作用仅包括疏水作用。C₁、C₂和C₃在BSA中存在两个结合位点，分别位于TRP134残基附近的亲水表面和TRP213残基附近的疏水空腔，其中分子间相互作用包括了氢键作用、疏水作用和静电作用。

(5) 单/双吡啶酰腙及其金属配合物的抑菌活性

L₁、L₂和L₃对大肠杆菌、枯草芽孢杆菌、金黄色葡萄球菌和铜绿假单胞菌均表现出抑制活性。L₁、L₂和L₃对枯草芽孢杆菌的抑制活性比对其它3种细菌的强，其中L₃对枯草芽孢杆菌的抑制活性强于L₁和L₂。

L₄仅在最高浓度下对大肠杆菌有微弱的抑制活性，而对其它3种细菌无任何抑制活性。C₁对铜绿假单胞菌无抑制活性，而对其它3种细菌表现出良好的抑制活性。C₂和C₃对四种细菌的生长都表现出良好的抑制活性。

Acylhydrazone and its metal complexes show good biological activities, such as anti-cancer, anti-virus, anti-microbial, anti-inflammatory and anti-oxidation, which has attracted wide attention. In this paper, three kinds of mono-pyridyl hydrazone compounds, one kind of bi-pyridyl hydrazone compounds and three kinds of bi-pyridyl tetranuclear transition metal complexes were designed and synthesized, and their binding properties with calf thymus DNA (CT-DNA) and bovine serum albumin (BSA) as well as antibacterial activities in vitro were studied. 

The main work of this paper is as follows:

(1) Synthesis of mono-/di- pyridyl hydrazone and their metal complexes

Three halogenated pyridyl hydrazones, namely 4-chlorobenzaldehyde-4- chloropyridine-2-formyl acylhydrazone (C₁₃H₉Cl₂N₃O, L₁), 4-bromobenzaldehyde-4- chloropyridine-2-formyl acylhydrazone (C₁₃H₉BrClN₃O, L₁) and 4-iodobenzaldehyde-4- chloropyridine-2-formyl acylhydrazone (C₁₃H₉ClIN₃O, L₁), as well as a bipyridyl acylhydrazone and its three complexes, namely 2-acetylpyridine-4- chloropyridine-2-carbonyl hydrazone (L₄), copper complex of L₄ {C₅₂H₄₀Cl₄Cu₄N₂₀O₁₆, [Cu₄(NO₃)₂(dp-L₄)₄](NO₃)₂, C₁}, cobalt complex of L₄ {C₅₄H₄₈Cl₄Co₄N₂₀O₁₈, [Co₄(NO₃)₂(H₂O)(C₂H₅OH)(dp-L₄)₄](NO₃)₂, C₂} and zinc complex of L₄ {C₅₄H₄₈Cl₄N₂₀O₁₈Zn₄, [Zn₄(NO₃)₂(H₂O)(C₂H₅OH)(dp-L₄)₄](NO₃)₂, C₃} have been synthesized.

(2) Structural characterization of mono-/di- pyridyl hydrazone and their metal complexes

The structures of L₁, L₂, L₃, L₄, C₁, C₂ and C₃ were characterized by elemental analysis, IR, ¹H NMR and X-ray single crystal diffraction. The results of X-ray single crystal diffraction showed that L₁, L₂ and L₃ crystallized in monoclinic lattice with space group Cc, L₄ crystallized in monoclinic lattice with space group P2₁/c, and they all existed in the keto form; C₁, C₂ and C₃ crystallized in triclinic lattice with P-1 space group, and the ligands involved in coordination (dp-L₄) all existed in the deprotonated enol form. Besides, C₁, C₂ and C₃ were all tetranuclear complex. 

(3) Study on the interactions of mono-/di- pyridyl hydrazones and their metal complexes with CT-DNA

L₁, L₂ and L₃ interacted with CT-DNA via the groove-binding mode, and the binding processes were spontaneous. The order of binding affinities was L₃ > L₂ > L₁. The intermolecular interactions of L₁, L₂ and L₃ with DNA included hydrogen bonding and hydrophobic interactions.

C₁, C₂ and C₃ bound with CT-DNA through the intercalative mode, while L₄ interacted with CT-DNA via a groove-binding mode. The order of binding affinities was: C₁ > C₂ > C₃ > L₄. The binding processes were spontaneous endothermic processes with entropy increasing. The intermolecular interactions of L₄ binding with CT-DNA included hydrogen bonding and hydrophobic interactions, and that of C₁, C₂ and C₃ binding with CT-DNA included hydrogen bonding, hydrophobic interactions and electrostatic interactions.

(4) Study on the interactions of mono-/di- pyridyl hydrazone and their metal complexes with BSA

L₁, L₂ and L₃ can effectively bind with BSA effectively, and the order of binding affinities was: L₃ > L₂ > L₁. The only binding sites of L₁, L₂ and L₃ in BSA were all located in the hydrophobic cavity near TRP213 residue. The intermolecular interactions included hydrogen bonding, halogen bonding and hydrophobic interactions. In the docking results, TRP213 residues participated in the hydrophobic interactions between L₁, L₂ and L₃ with BSA, which was the main reason for the fluorescence quenching of BSA. In addition, iodine-oxygen halogen bond was stronger than chlorine-oxygen and bromine-oxygen bond.

The order of binding affinities of L₄, C₁, C₂ and C₃ to BSA was: C₁ > C₃ > C₂ > L₄. The binding processes were all spontaneous endothermic processes with entropy increasing. The only binding site of L₄ in BSA was located in the hydrophobic cavity near TRP213 residue, and their interactions only included hydrophobic interactions. There are two binding sites of C₁, C₂ and C₃ in BSA, which were located in the hydrophilic surface near TRP134 residue and the hydrophobic cavity near TRP213 residue, respectively. The intermolecular interactions included hydrogen bonding, hydrophobic and electrostatic interactions.

(5) The antibacterial activities of mono-/di- pyridyl hydrazones and their metal complexes

L₁, L₂ and L₃ exhibited inhibitory activities on E. coli, B. subtilis, S. aureus and P. aeruginosa. The inhibitory activities of L₁, L₂ and L₃ against B. subtilis were slightly higher than that of them against the other three bacteria, and the inhibitory activity of L₃ against B. subtilis was higher than that of L₁ and L₂.

L₄ had weak inhibitory activity on E.coli at the highest concentration, but no inhibitory activity on other three kinds of bacteria. C₁ has strong inhibitory activity against E. coli, S. aureus and B. subtilis, but no inhibitory activity on P. aeruginosa. C₂ and C₃ have strong inhibitory effects on four bacteria.