Computer Simulation for Effect of Tb3 + on Ca2 +

R eceived date :2001-02-26;revised date :2001-07-10

Foundation item :Project Supported by the National Natural Science Foundation of China (29890280,29971029)Biography :Lu X ing (1975-),Male ,Master 3Correspondent (E 2mail :ldq @https://www.360docs.net/doc/c815625349.html, )

Computer Simulation for E ffect of Tb 3+on C a 2+Speciation in Human Plasma

Lu Xing (卢　兴),Wang Yue (王　悦),Zhang Haiyuan (张海元),Wang Jinping (王进平),Niu Chunji (牛春吉)3,Ni Jiazuan (倪嘉缵)

(Key L aboratory of Rare Earth Chemistry and Physics ,Changchun Institute of Applied Chemistry ,Chinese Academy of Sciences ,Changchun 130022,China )

Abstract :E ffect of Tb 3+on Ca 2+speciation in human plasma was studied by means of the computer program of MINTEQA2.When Tb 3+ions are not added into the system ,Ca 2+ions mostly distribute in free Ca 2+(74.7%)and the surplus distributes in Ca 2+complexes ,such as [CaHCO 3]+(7.9%),[Ca (Lac )]+(6.4%),CaHPO 4(113%),[CaHistidinateThreoninateH 3]3+(2.4%),[CaCitrateHistidinateH 2](2.3%)and CaCO 3(1.1%).Tb 3+can compete with Ca 2+for inorganic as well as biological ligands.An increase of concentration of Tb 3+in the system results in an increase of content of free Ca 2+and a decrease of contents of Ca 2+complexes.

K ey words :rare earths ;computer simulation ;speciation ;human plasma ;calcium ;terbium CLC number :O614.33;Q592.1 Document code :A Article ID :1002-0721(2002)03-0238-03

Because of the excellent spectroscopic and magnetic properties of tri 2positive lan 2thanide ions coupled with the similarities be 2tween them and Ca 2+ion particularly with re 2gard to ionic radii ,ligand exchange rates and coordination numbers [1],many studies have fo 2cused on application of lanthanide probes for Ca 2+in biological systems [2].On the other hand ,it is well known that displacement of Ca 2+from biological molecules by lanthanide ions is closely concerned with biological effects of lanthanides.For example ,the displacement of Ca 2+by lanthanide ions affects some enzyme activities.Therefore the research on the effect of lanthanides on Ca 2+species is a key to ex 2ploring the distribution ,metabolism and bio 2logical effects of lanthanides in organisms ,also it is very important to elucidating the effects of lanthanides on health and environment.For some complex systems ,such as human plasma and other biological fluids ,computer simula 2tion has been used to study the distribution of species because of the absence of direct accu 2

rate analysis methods [3].Jackson et al.[4]published the speciation of biological metal ions and Gd 3+ions in plasma using May ′s sin 2gle 2phase model ,but some stability constants used in his model were estimated and the in 2soluble species were not considered because of his single 2phase model.Webb studied the spe 2ciation of Gd 3+and Cm 3+in the digestive tract to see whether Gd 3+can be used as a surrogate for Cm 3+,and the insoluble species of both metals were not considered either [5].In this article ,we developed a multi 2phase model of human plasma and the precipitates of Tb 3+were considered.S ome new results were ob 2tained.

1　Methods

1.1　Multi 2phase model of human plasma May ′s model [6]is a single 2phase model ,so it can not be used to study the effect of lan 2thanide ions on Ca 2+speciation in human plas 2ma.We improved May ′s model and developed a multi 2phase model of human plasma.PO 43-

JOURNAL O F RAR E E ARTHS 2002　Vol.20　No.3

and CO32-are important ligands in human plasma,and lanthanides prefer to bind them than bind biological molecules[7,8].Therefore, PO43-and CO32-were included in the multi2 phase model.Human serum transferring(T f), human serum albumin(HSA)and im2 munoglobin G(IgG)were added into this mod2 el because their complexes with lanthanides are quite stable.The logarithm values of the sta2 bility constants of their complexes with Tb3+ are:[Tb(T f)],11.20;[Tb2(T f)], 18181[9];[Tb(HSA)],～6.5[1];[Tb (IgG)],3.7[1].In addition,the model con2 tained almost all the important low2molecular2 weight biological ligands which consist of amino acids,carboxylic acids and hydroxy2car2 boxylic acids.Only a few low2molecular2weight biological ligands were not included because either their concentrations are comparatively low or their binding constants with metal ions are rather small,such as histaminate whose concentration in human plasma is only3×10-8mol?L-1and logarithm value of the bind2 ing constant with Gd3+is just0.9.There are more than400species in this model.This model is superior to the previous single2phase models because the precipitate species of Tb3+ can be calculated.

A lot of accurate stability constants of bi2 nary and ternary complexes of metal ions (Pr3+,Gd3+,Tb3+,Yb3+,Ca2+and Zn2+) with biological ligands were determined under physiological conditions by potentiometry in our group,and some were used in this study[10～12].The logarithm values of the sta2 bility constants of main Ca2+species are listed below:[CaHCO3]+,11.33;CaCO3(aq), 3115;CaHPO4,15.085;[CaPO4]-,6.459; [Ca(Cit)]-,6.637;[Ca(Lac)]+,2.332; [CaHisThrH3]3+,33.095;[CaCitHisH2], 25.997.

The concentration of the exchangeable Ca2+in human plasma is 1.460×10-3 mol?L-1[6]and it is used in our simulation. All our simulations are processed under physio2 logical conditions(θ=37℃,I=0.15NaCl) and p H7.40.

1.2　C omputer program The computer program of MINTEQA2used to simulate the speciation in human plasma was developed by U.S.Environment Protection Agency in1991. 2　Results and discussion

E ffect of Tb3+on Ca2+speciation is listed in Table1.The data show that all the species of Ca2+are soluble.In the absence of Tb3+, 74.7%of Ca2+ions are free,10.3%dis2 tribute in carbonate and phosphate and the rest exists as[Ca(Lac)]+,[CaHisThrH3]3+and [CaCitHisH2].Below or at the concentration

T able1　E ffect of Tb3+on distribution of Ca2+species in human plasma(%)

Species3T otal concentration of Tb3+/(m ol?L-1)

0 1.000×10-6 3.744×10-4 1.667×10-2 4.000×10-2

Ca2+74.77417751984199418 [CaHCO3]+7.9719810<110<110 CaCO3(aq)111111111<110<110 CaHPO4113113<110<110<110 [CaPO4]-<110<110<110<110<110 [Ca(Cit)]-<110<110<110<110<110 [Ca(Lac)]+614614615712114 [CaHisThrH3]3+214214214317310 [CaCitHisH2]213213213<110<110 TbPO40100100212019 Tb2(CO3)300096184018 soluble Tb(Ⅲ)0001105813 3His=histidinate;Thr=threoninate;Cit=citrate;Lac=lactate 932

No.3 Computer Simulation for E ffect of Tb3+on Ca2+Speciation in Human Plasma

of3.744×10-4mol?L-1which equals to the concentration of phosphate in human plasma, Tb3+ions are almost completely bound to phosphate to form precipitate of TbPO4[7,8]and have little effect on Ca2+species except CaH2 PO4.As the total concentration of Tb3+in2 creases further,available phosphate ions are exceeded and the surplus Tb3+ions are bound to carbonate to form another kind of precipitate of Tb2(CO3)3,which causes the contents of CaHPO4,CaCO3(aq),[CaHCO3]+and [CaCitHisH2]decrease while the contents of free Ca2+ions,[Ca(Lac)]+and [CaHisThrH3]3+increase.Because the con2 centration of lactate is rather high in the system and the stability constant of[CaHisThrH3]3+ is relatively large,thus the Ca2+previously bound to phosphate and carbonate now begin to form[Ca(Lac)]+and[CaHisThrH3]3+,and also some exist as free Ca2+.But as the total concentration of Tb3+reaches 4.000×10-2 mol?L-1,the contents of[Ca(Lac)]+and [CaHisThrH3]3+also decrease because the concentration of soluble Tb3+is high enough to compete with Ca2+for lactate,histidinate and threoninate.

The simulation results show that Tb3+can compete with Ca2+for phosphate and carbonate as well as some biological ligands,such as cit2 rate,lactate,histidinate and threoninate in human plasma.In the presence of Tb3+,the concentration of free Ca2+increases and the concentrations of Ca2+complexes decrease.

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