密度泛函理論方法研究鋁-麥芽酚配合物的形態(tài)結(jié)構(gòu)與水交換反應(yīng)

張婧，董紹楠，侯曉霞，畢樹(shù)平

南京大學(xué)化學(xué)化工學(xué)院，南京 210023

密度泛函理論方法研究鋁-麥芽酚配合物的形態(tài)結(jié)構(gòu)與水交換反應(yīng)

張婧，董紹楠，侯曉霞，畢樹(shù)平*

南京大學(xué)化學(xué)化工學(xué)院，南京 210023

鋁-麥芽酚配合物；密度泛函理論；鋁形態(tài)結(jié)構(gòu)；水交換反應(yīng)；致毒機(jī)制

Received14 January 2017accepted31 May 2017

Keywords: aluminium(III)-maltolate complexes; density functional theory (DFT); the structures and speciation of aluminium; water-exchange reaction; toxicity mechanism

鋁具有很強(qiáng)的神經(jīng)毒性，被認(rèn)為是導(dǎo)致阿爾茲海默病等神經(jīng)退行性疾病的重要因素之一，其毒性大小與鋁化合物的種類(lèi)及形態(tài)有關(guān)[1]。麥芽酚(maltolate，簡(jiǎn)寫(xiě)為ma)是一種廣泛用于食品添加劑的天然產(chǎn)物[2]，易與水溶液中Al3+結(jié)合生成具有水溶性和脂溶性的電中性配合物[3]。鋁-麥芽酚配合物在不同配比、pH等環(huán)境因素下具有多種形態(tài)，而Al3+的毒性與鋁-麥芽酚配合物的賦存形態(tài)密切相關(guān)。麥芽酚配體增強(qiáng)了Al3+的膜通透性，進(jìn)而提高了Al3+的生理活性和生物利用度[3]。Al3+進(jìn)入細(xì)胞內(nèi)作用于神經(jīng)元、神經(jīng)膠質(zhì)細(xì)胞和DNA磷酸基團(tuán)[3]等位點(diǎn)進(jìn)而造成神經(jīng)損傷[4]。國(guó)內(nèi)外課題組[4-9]主要采用核磁共振、紅外光譜、紫外光譜和質(zhì)譜等實(shí)驗(yàn)方法對(duì)鋁-麥芽酚體系進(jìn)行研究，但由于現(xiàn)有實(shí)驗(yàn)條件的自身限制、準(zhǔn)確解析和歸屬光譜的難度以及無(wú)法準(zhǔn)確檢測(cè)低濃度化合物的現(xiàn)狀，使得這些研究難以區(qū)分鋁-麥芽酚配合物的不同形態(tài)結(jié)構(gòu)以及準(zhǔn)確判斷反應(yīng)活性位點(diǎn)。量子化學(xué)計(jì)算方法為解決這一難題提供了新的思路[10]。本文采用密度泛函理論計(jì)算方法對(duì)鋁-麥芽酚體系進(jìn)行系統(tǒng)研究，主要工作從靜態(tài)結(jié)構(gòu)、動(dòng)態(tài)水交換反應(yīng)和不同鋁形態(tài)與致毒機(jī)制的關(guān)聯(lián)探討3個(gè)方面進(jìn)行：(1) 在超分子-極化連續(xù)(GP-SM-PCM)模型下優(yōu)化鋁-麥芽酚配合物靜態(tài)結(jié)構(gòu)得到鍵長(zhǎng)、鍵角、NPA電荷和能量等參數(shù)，計(jì)算得到Al(ma)3配合物4種異構(gòu)體的核磁共振、紫外和紅外等光譜學(xué)數(shù)據(jù)并與文獻(xiàn)實(shí)驗(yàn)值比較；(2) 模擬1∶1和1∶2鋁-麥芽酚配合物各種可能位點(diǎn)的水交換反應(yīng)，通過(guò)計(jì)算得到的相關(guān)結(jié)構(gòu)-能量參數(shù)預(yù)測(cè)不同構(gòu)型各位點(diǎn)的水交換速率，并與文獻(xiàn)報(bào)道的實(shí)驗(yàn)值進(jìn)行對(duì)比；(3) 探討鋁-麥芽酚配合物不同形態(tài)與轉(zhuǎn)化以及水交換反應(yīng)速率與Al3+生物有效性的關(guān)系和致毒機(jī)制。

1 原理與計(jì)算方法(Theory and calculation methods)

所有計(jì)算在Gaussian 03程序包中運(yùn)行。所有結(jié)構(gòu)均采用密度泛函理論(DFT)在B3LYP/6-311+G(d,p)基組水平下進(jìn)行優(yōu)化及頻率計(jì)算。原子電荷由自然布居分析(NPA)得到，單點(diǎn)能采用MP2方法在相同基組水平下進(jìn)行計(jì)算[10]。本文中所有構(gòu)型的優(yōu)化、頻率和單點(diǎn)能計(jì)算均在0 K下進(jìn)行，熱力學(xué)計(jì)算在298.15 K和1 atm下進(jìn)行。

圖1 鋁-麥芽酚配合物的10種可能靜態(tài)構(gòu)型Fig. 1 Ten possible static configurations of the Al-maltolate complexes

2 結(jié)果與討論(Results and discussion)

2.1 鋁-麥芽酚配合物的靜態(tài)結(jié)構(gòu)

圖2為優(yōu)化得到的1∶1、1∶2和1∶3鋁-麥芽酚配合物10種靜態(tài)構(gòu)型。以赤道面左下角O原子為起點(diǎn)，逆時(shí)針編號(hào)1-4，赤道面上方O原子為編號(hào)5，下方O原子編號(hào)為6。計(jì)算所得的鍵長(zhǎng)、鍵角、NPA電荷和能量等參數(shù)見(jiàn)表1，Al(ma)3配合物4種異構(gòu)體的NMR、UV-vis、IR等數(shù)據(jù)和譜圖分別見(jiàn)表2和3及圖3和4。

(1)結(jié)構(gòu)特征。以相同模型方法基組下優(yōu)化得到的Al(H2O)63+團(tuán)簇(Nm=12)為本底(Al-OH2鍵長(zhǎng)1.916 ?)，鋁-麥芽酚1∶1配合物的平均Al-OH2鍵長(zhǎng)(1.923 ?)稍有拉長(zhǎng)，其中配體鄰位Al-OH2鍵長(zhǎng)為1.947 ?，對(duì)位平均鍵長(zhǎng)為1.899 ?，表明麥芽酚配體增加了鄰位水分子的不穩(wěn)定性，同時(shí)穩(wěn)定了對(duì)位水分子。1∶2配合物3個(gè)cis結(jié)構(gòu)的Al-OH2鍵長(zhǎng)(1.906～1.914 ?)與本底Al-OH2鍵長(zhǎng)相差不大，分析可能原因?yàn)榕潴w對(duì)其鄰位活化與對(duì)位鈍化效應(yīng)相互抵消。1∶2配合物2個(gè)trans結(jié)構(gòu)的Al-OH2鍵長(zhǎng)(1.946～1.948 ?)和Al(H2O)63+團(tuán)簇的Al-OH2鍵長(zhǎng)(1.916 ?)相比明顯增加，說(shuō)明配體的加入一定程度上增強(qiáng)了配位水分子反應(yīng)活性，分析原因?yàn)榕潴w的鄰位活化效應(yīng)。由于A(yíng)l(ma)3具有水溶性[3]，故外層添加的6個(gè)水分子穩(wěn)定在第二水化層并且與配位O原子形成氫鍵，4個(gè)構(gòu)型的平均Al-O鍵長(zhǎng)在1.934～1.939 ?之間，與Al(H2O)63+團(tuán)簇相比增加了0.02 ?左右。通過(guò)分析1∶1、1∶2和1∶3鋁-麥芽酚配合物不同形態(tài)結(jié)構(gòu)的3個(gè)特征鍵角，發(fā)現(xiàn)所有形態(tài)均為六配位，其中赤道鍵角∠O1-Al-O2與∠O1-Al-O3在90°和175°左右，軸向鍵角∠O5-Al-O6在175°左右，構(gòu)型為變形八面體。

(2)NPA電荷特征。如表1所示，隨著配體數(shù)目的增加，鋁-麥芽酚配合物的中心Al原子上正電荷逐漸減小(1.938 e→1.932 e→1.919 e)，其中trans構(gòu)型的1∶2配合物比1∶1配合物減少了0.01 e，1∶3構(gòu)型比1∶1構(gòu)型減少了0.019 e。分析原因可能為，隨著配體的加入體系形成了更大的共軛體系導(dǎo)致電荷進(jìn)一步分散。

圖2 鋁-麥芽酚配合物優(yōu)化得到的10種靜態(tài)構(gòu)型Fig. 2 The ten optimized static configurations of Al-maltolate complexes

表1 鋁-麥芽酚配合物10種靜態(tài)構(gòu)型的結(jié)構(gòu)、NPA電荷和能量參數(shù)Table 1 Structural parameters, NPA charges and energies for ten static configurations of Al-maltolate complexes

注：∠O1-Al-O2和∠O1-Al-O3為赤道鍵角；∠O5-Al-O6為軸向鍵角；a鋁與螯合O的平均鍵長(zhǎng)；b鋁與配體麥芽酚中4-吡喃酮O的(平均)鍵長(zhǎng)；c鋁與麥芽酚中3-羥基O的(平均)鍵長(zhǎng)；dAl-OH2平均鍵長(zhǎng)；eAl-OH2(cis)的平均鍵長(zhǎng)；fAl-OH2(trans)的平均鍵長(zhǎng)；g螯合O的平均NPA電荷；h4-吡喃酮O的(平均)NPA電荷；i3-羥基O的(平均)NPA電荷；j配位H2O中O的平均NPA電荷。

Note: ∠O1-Al-O2and ∠O1-Al-O3are the equatorial bond angles; ∠O5-Al-O6is the axial bond angle;athe average Al-O bond length between Al and chelated O;bthe (average) Al-O bond length between Al and 4-pyronate O;cthe (average) Al-O bond length between Al and 3-oxy O;dthe average Al-OH2bond length;ethe average Al-OH2(cis) bond length;fthe average Al-OH2(trans) bond length;gthe average NPA charge of chelated O;hthe (average) NPA charge of 4-pyronate O;ithe (average) NPA charge of 3-oxy O;jthe average NPA charge of O in H2O.

圖3 Al(ma)3配合物在水溶液中的紫外吸收光譜圖Fig. 3 The UV spectrums of Al(ma)3 complexes in aqueous solution

(4)光譜學(xué)特征。由表2中27Al NMR和1H NMR數(shù)據(jù)可以看出，計(jì)算得到的化學(xué)位移與實(shí)驗(yàn)值基本一致，說(shuō)明GP-SM-PCM模型適合用于處理鋁-麥芽酚配合物體系。如表3以及圖3所示，Al(ma)3的4種同分異構(gòu)體計(jì)算得到的紫外最大吸收波長(zhǎng)～ 300 nm，與實(shí)驗(yàn)值305 nm相符。根據(jù)圖4所示紅外光譜圖，選取特征Al-O振動(dòng)、配體環(huán)中C=C振動(dòng)以及C-H振動(dòng)進(jìn)行對(duì)比，以Λ-fac-Al(ma)3為例，文獻(xiàn)中Al-O最強(qiáng)振動(dòng)發(fā)生在410 cm-1和445 cm-1處，理論計(jì)算得到的Al-O振動(dòng)主要在423～462 cm-1之間，兩者基本相符。

表2 1∶3鋁-麥芽酚配合物的27Al NMR和1H NMR計(jì)算結(jié)果aTable 2 27Al NMR and 1H NMR shielding constants and chemical shifts (ppm) of Al(ma)3 a

注：a 27Al的Al(H2O)63+參比屏蔽常數(shù)為572.6 ppm (δ = 0 ppm)，1H的四甲基硅烷(TMS)參比屏蔽常數(shù)為32.0 ppm(δ = 0 ppm)；b實(shí)驗(yàn)中得到的27Al NMR數(shù)據(jù)無(wú)法區(qū)分4種異構(gòu)體；c甲基中的H原子；d4-吡喃O相鄰C原子上鍵合的H原子；e3-羰基O對(duì)位的C原子上鍵合的H原子。

Note:aReference shielding constants of Al(H2O)63+and tetramethyl silane (TMS) are 572.6 ppm (δ = 0 ppm) and 32.0 ppm (δ = 0 ppm) respectively;bThe isomers of Al(ma)3cannot be distinguished in the experiments;cH atom in the methyl group;dH atom is bonded to the C atom which is next to 4-pyronate oxygen;eH atom is in the para-position to 3-oxy oxygen.

表3 1∶3鋁-麥芽酚配合物的紫外和紅外計(jì)算結(jié)果Table 3 The calculated ultraviolet spectral data and infrared absorptions of Al(ma)3

注：a文獻(xiàn)[8]中檢測(cè)紫外光譜時(shí)溶劑為飽和正辛醇的水溶液；b吸光度ε的單位為(mol·L-1)-1·cm-1。

Note:aThe solvent is water saturated with n-octanol for UV in reference [8];bthe unit for ε is (mol·L-1)-1·cm-1.

圖4 Al(ma)3配合物的紅外光譜圖Fig. 4 The IR spectrums of Al(ma)3 complexes

2.2 鋁-麥芽酚配合物的水交換反應(yīng)

表4 1∶1/1∶2鋁-麥芽酚配合物水交換反應(yīng)的結(jié)構(gòu)參數(shù)(?)Table 4 Structural parameters for the water-exchange reaction of 1:1/1:2 Al-maltolate complexes (?)

注：aAl與配位水中O原子的鍵長(zhǎng)；bAl與離去水中O原子的鍵長(zhǎng)；cAl與配位水中O原子的平均鍵長(zhǎng)；dAl與配體麥芽酚中4-吡喃酮O (表示為Op)的(平均)鍵長(zhǎng)；eAl與配體麥芽酚中3-羥基O (表示為Oo)的(平均)鍵長(zhǎng)；fAl-O鍵長(zhǎng)總和；g△Σ(Al-Ligand) = Σ(Al-Ligand)transition state- Σ(Al-Ligand)reactant。

Note:aThe Al-O bond length between Al and the O atom of coordinated water molecules;bthe Al-O bond length between Al and the O atom of leaving water molecule;cthe average Al-OH2bond length;dthe (average) Al-O bond length between Al and 4-pyronate O (Op);ethe (average) Al-O bond length between Al and 3-oxy O (Oo);fthe sum of Al-O bond length;g△Σ(Al-Ligand) = Σ(Al-Ligand)transition state- Σ(Al-Ligand)reactant.

以鋁-麥芽酚配合物1∶1構(gòu)型離去水位于配體鄰位(cis to ma)的水交換反應(yīng)為例，反應(yīng)物中離去水和中心Al原子的距離為2.040 ?，軸向鍵角∠O4-Al1-O5為175.7°，赤道鍵角∠O2-Al1-O3與∠O2-Al1-O6分別為174.9°和87.0°，為一具有八面體結(jié)構(gòu)的六配位化合物。隨著水交換反應(yīng)的進(jìn)行，水分子逐漸離去到達(dá)過(guò)渡態(tài)，此時(shí)Al-OL距離為2.815 ?，且該水分子上O原子與另一配位水分子上H原子形成氫鍵(1.961 ?)，虛頻(-85.25 cm-1)下離去水分子在第一和第二水化層之間振動(dòng)，水交換反應(yīng)過(guò)程中軸向鍵角∠O4-Al1-O5基本不變化(175.7°→174.5°)，赤道鍵角∠O2-Al1-O3明顯減小(174.9°→147.9°)，此時(shí)過(guò)渡態(tài)構(gòu)型傾向于三角雙錐結(jié)構(gòu)。之后離去水分子進(jìn)一步遠(yuǎn)離Al離子進(jìn)入第二水化層形成五配位產(chǎn)物(Al-OL距離為3.872 ?)，此時(shí)軸向鍵角∠O4-Al1-O5變化很小(174.5°→173.9°)，赤道鍵角∠O2-Al1-O3與∠O2-Al1-O6分別變?yōu)?17.7°和111.8°，產(chǎn)物為具有三角雙錐結(jié)構(gòu)的五配位配合物。8條水交換反應(yīng)路徑(A→H)的Δ∑(Al-Ligand)均為正值，說(shuō)明鋁-麥芽酚配合物1∶1/1∶2構(gòu)型的水交換反應(yīng)均屬于解離活化機(jī)制[14]。

圖5 1∶1/1∶2鋁-麥芽酚配合物水交換反應(yīng)過(guò)渡態(tài)構(gòu)型圖(離去水以白色標(biāo)記)Fig. 5 The optimized transition state of the water exchange reaction for 1:1 and 1:2 Al-maltolate complexes (The leaving water molecules are white)

表5 1∶1/1∶2鋁-麥芽酚配合物水交換反應(yīng)的活化和反應(yīng)能量參數(shù)Table 5 The active and reaction energies for the water-exchange reaction of 1:1/1:2 Al-maltolate complexes

表6 3種方法預(yù)測(cè)鋁-麥芽酚配合物的水交換反應(yīng)速率logkex (s-1)Table 6 The predicted log kex (s-1) of Al-maltolate complexes by three methods

2.3 鋁-麥芽酚配合物毒性與其形態(tài)結(jié)構(gòu)之間關(guān)系的機(jī)理分析

致謝：本文的數(shù)值計(jì)算在南京大學(xué)高性能計(jì)算中心的IBM刀片式集群機(jī)上完成。

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InvestigationoftheConfigurationCharacteristicsandWater-ExchangeReactionsofAluminium(III)-MaltolateComplexesbyDensityFunctionalTheory

Zhang Jing, Dong Shaonan, Hou Xiaoxia, Bi Shuping*

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

10.7524/AJE.1673-5897.20170114005

2017-01-14錄用日期2017-05-31

1673-5897(2017)3-261-12

X171.5

A

畢樹(shù)平(1961-)，男，分析化學(xué)博士，教授，博士生導(dǎo)師，主要從事環(huán)境分析化學(xué)和環(huán)境表界面電化學(xué)研究。

國(guó)家自然科學(xué)基金(No.21177054)

張婧(1991-)，女，碩士研究生，研究方向?yàn)榄h(huán)境分析化學(xué)，E-mail: april_91@126.com;

*通訊作者(Corresponding author)， E-mail: bisp@nju.edu.cn

張婧, 董紹楠, 侯曉霞, 等. 密度泛函理論方法研究鋁-麥芽酚配合物的形態(tài)結(jié)構(gòu)與水交換反應(yīng)[J]. 生態(tài)毒理學(xué)報(bào)，2017, 12(3): 261-272

Zhang J, Dong S N, Hou X X, et al. Investigation of the configuration characteristics and water- exchange reactions of aluminium(III)-maltolate complexes by density functional theory [J]. Asian Journal of Ecotoxicology, 2017, 12(3): 261-272 (in Chinese)