Environmental effects on the structure of metal ion-DOTA complexes: an ab initio study of radiopharmaceutical metals

Quantum chemical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA, but Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the resulting structures show a large variation between the Y and In ions. A six-residue model of the active site containing metal ion-DOTA showed that the Y-DOTA structure optimized to a structure similar to the crystal structure but that the water molecule in In-DOTA disrupts the salt bridge between Arg98B and a carboxylate side chain of DOTA. These observed differences could in part explain the differential binding constants for Y-DOTA and In-DOTA to the antibody 2D12.5.     

Long-range-distance NMR effects in a protein labeled with a lanthanide-DOTA chelate

A two-thiol reactive lanthanide-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) chelate, CLaNP-3 (CLaNP=caged lanthanide NMR probe), was synthesized for the rigid attachment to cysteine groups on a protein surface, and used to obtain long-range-distance information from the {15N,1H} HSQC spectra of the protein-lanthanide complex. The DOTA ring exhibits several isomers that are in exchange; however, single resonances were observed for most amide groups in the protein, allowing determination of a single, apparent magnetic-susceptibility tensor. Pseudocontact shifts caused by Yb-containing CLaNP-3 were observed for atoms at 15-35 A from the metal. By using Gd-containing CLaNP-3, relaxation effects were observed, allowing distances up to 30 A from the paramagnetic center to be determined accurately. Similar results were obtained with a Gd-DTPA (diethylene-triaminepentaacetic acid) chelate, CLaNP-1, bound in the same bidentate manner to the protein. This study demonstrates that bidentate attachment of a paramagnetic probe enables determination of long-range distances.     

表皮生长因子受体和抑制剂之间分子对接的研究

研究了表皮生长因子受体(EGFR)和4-苯胺喹唑啉类抑制剂之间的相互作用模式，表皮生长因子受体的三维结构通过同源蛋白模建的方法得到，而抑制剂和靶酶结合复合物结构则通过分子力学和分子动力学结合的方法计算得到。从模拟结果得到的抑制剂和靶酶之间的相互作用模式表明范德华相互作用、疏水相互作用以及氢键相互作用对抑制剂的活性都有重要的影响，抑制剂的苯胺部分位于活性口袋的底部，能够与受体残基的非极性侧链产生很强的范德华和疏水相互作用，抑制剂双环上的取代基团也能和活性口袋外部的部分残基形成一定的范德华和疏水性相互作用，而抑制剂喹唑啉环上的氮原子能和周围的残基形成较强的氢键相互作用，对抑制剂的活性有较大的影响，计算得到抑制剂和靶酶之间的非键相互作用能以及抑制剂和靶酶之间的相互作用信息能够很好地解释抑制剂活性和结构的关系，为全新抑制剂的设计提供了重要的结构信息。     

Hierarchical assembly of homochiral porous solids using coordination and hydrogen bonds

A family of homochiral metal carboxylate coordination polymers have been synthesized by treating 2,2'-dihydroxy-1,1'-binaphthalene-6,6'-dicarboxylic acid (H(2)BDA) with metal salts at elevated temperatures. BDA ligands link adjacent metal centers to form 1D coordination polymeric chains using the carboxylate functionality, while the hydroxyl groups of BDA ligands form H-bonds with carboxylate oxygen atoms to link 1D coordination polymeric chains into open frameworks of higher dimensionality. We also present evidence for the important role played by H-bonds in the stabilization of open framework structures which allows for the hierarchical assembly of chiral porous solids.     

A rare earth-DOTA-binding antibody: probe properties and binding affinity across the lanthanide series

An antibody that binds rare earth complexes selectively could be used as a docking station for a set of probe molecules, of particular interest for medical imaging and therapy. The rare earths are rich in probe properties, such as the paramagnetism of Gd, the luminescence of Tb and Eu, and the nuclear properties of Lu and Y. We find that antibody 2D12.5, initially developed to bind analogues of Y-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N' ',N' '-tetraacetic acid) for radiotherapy, binds not only Y-DOTA analogues but also analogous DOTA complexes of all of the lanthanides. Surprisingly, chelates of some metals such as Gd3+ bind more tightly than the original Y3+ complex. When the shape of the complex is perturbed by either increasing or decreasing the radius of the lanthanide ion, the thermodynamic stability of the protein-ligand complex changes in a regular fashion. The behavior of DeltaDeltaG as a function of ionic radius fits a parabola, as might be expected for a system that behaves in a thermodynamically elastic way. The broad specificity and high affinity of this antibody for all rare earth-DOTA complexes make it particularly interesting for applications that take advantage of the unique characteristics of lanthanides. For example, UV excitation of the Tb-DOTA-2D12.5 complex leads to energy transfer from aromatic side chains of the antibody to bound Tb-DOTA, enhancing green terbium luminescence >104 relative to unbound Tb-DOTA.     

Chelators for radioimmunotherapy: I. NMR and ab initio calculation studies on 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr)

This work describes the modification of the chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N' ',N' "-tetraacetic acid (DOTA) to improve the rate of metal loading for radioimmunotherapy applications. Previous ab initio calculations predicted that the compounds 1,4,7,10-tetra(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO4Pr) and 1,4,7-tris(carboxymethyl)-10-(carboxyethyl)-1,4,7,10-tetraazacyclododecane (DO3A1Pr) have a ca. 2000-fold improvement in yttrium metal loading rates compared to those of DOTA (Jang, Y. H.; Blanco, M.; Dasgupta, S.; Keire, D. A.; Shively, J. E.; Goddard, W. A., III. J. Am. Chem. Soc. 1999, 121, 6142-6151). In this study, we report the synthesis, purification, (1)H-NMR chemical shift assignments, pK(a) values, metal loading rate measurements, and additional ab initio calculations of these two compounds. The yttrium loading rates of DO3A1Pr are approximately twice those of DOTA, at pH 4.6 and 37 degrees C. The NMR data indicates that the DO4Pr analogue forms a stable type I complex but does not form a type II complex. The new ab initio calculations performed on DO4Pr and DO3A1Pr indicate that the rate-determining step is the deprotonation of the first macrocycle amine proton, not the second proton as assumed in the previous calculations. The new calculations predict an improvement in the rate of metal loading that more closely matches the experimentally observed change in the rate.     

Preferential formation of the different hydrogen bonds and their effects in tetrahydrofuran and tetrahydropyran microhydrated complexes

The role of cycloether-water (c-w) and water-water (w-w) hydrogen bonds (H-bonds) on the stability of the tetrahydrofuran THF/(H(2)O)(n) and the tetrahydropyran THP/(H(2)O)(n) complexes with n = 1-4 was investigated herein using the density functional and ab initio methods and the atoms in molecules theory. Geometry optimizations for these complexes were carried out with various possible initial guess structures. It was revealed that the major contributions of the mono and dihydrated complexes came from c-w H-bonds. A competition between c-w and w-w H-bonds contribution was observed for trihydrated complexes. For most of tetrahydrated complexes, the inter-water H-bonds provided the greatest contribution, whereas the c-w contributions were small but not negligible. It was confirmed that to produce a hydrophobic hydration of cycloethers, the C-H···O(w) H-bond should be associated with a network of H-bonds that connects both portions of the solute, through the formation of a bifunctional H-bond. A linear correlation is obtained for the sum of electron density at the bond critical points (ρ(b)) with the interaction energy (ΔE) and with the solute-solvent interaction energy (ΔE(s-w)) of the microhydrated complexes. In addition, a new way to estimate the energetic contribution as well as the preferential formation of the different H-bonds based completely on ρ(b) was found. Even more, it allows to differentiate the contribution from c-w interactions in both hydrophilic and hydrophobic contributions, it is therefore a useful tool for studying the hydration of large biomolecules. The analysis of the modifications in the atomic and group properties brought about by successive addition of H(2)O molecules allowed to pinpoint the atoms or molecular groups that undergo the greatest changes in electron population and energetic stabilization. It was identified that the remarkable stabilization of the water oxygen atoms is crucial for the stabilization of the complexes.     

NMR investigation of the interaction of vanadate with carbasilatranes in aqueous solutions

Reaction of vanadate with carbasilatranes [methoxy{N,N',N' '-2,2',3-[bis(1-methylethanolato)(propyl)]amino}silane (1), methoxy{N,N',N' '-2,2',3-[bis(1-ethanolethanolato)(propyl)]amino}silane (2), and {N,N',N' '-2,2',2-[bis(ethanolato)(glycolpropyl ether)]amino}silane (3)] in aqueous solution results in the formation of vanadosilicates and five-coordinated chelate vanadium(V) complexes as evidenced by 51V, 1H, and 13C NMR spectroscopy. Chiral carbasilatrane S,S-1 was characterized in the solid state by X-ray diffraction, revealing a trigonal bipyramidal geometry around the metal ion, with one unidentate methoxy group and one atrane nitrogen atom at the axial positions and one carbon and two atrane oxygen atoms at the equatorial plane of the bipyramid. Crystal data (Mo Kalpha; 100(2) K) are as follows: orthorhombic space group P2(1)2(1)2(1); a = 8.8751(6), b = 9.7031(7), c = 14.2263(12) A; Z = 4. The complexation of vanadium either with 1 or 2 is stereoselective yielding approximately 94% of the complex containing ligand in the S,R-configuration. The lower ability of the S,S- and R,R-diastereoisomers of 1 and 2 to ligate vanadate was attributed to stereochemical factors, dictating a square pyramidal geometry for the chelated complexes. A dynamic process between the vanadium chelate complexes and the respective carbasilatranes was evaluated by 2D {1H} EXSY NMR spectroscopy. These spectra show that the vanadate complexes with the open carbasilatranes exchange more slowly with the free ligand compared to the respective alcohol aminate complexes.     

含dmpzm配体的锌和镉配合物的合成、结构及性质研究

通过M(NO₃)₂(M=Zn，Cd)和二(3，5-二甲基吡唑)甲烷(dmpzm)的反应，合成了2个锌和镉配合物[M(dmpzm)₂(NO₃)][NO₃](1：M=Zn；2：M=Cd)。配合物1和2经元素分析,红外光谱表征，并经X射线单晶衍射法证实。配合物1属于正交晶系，空间群为Pca2₁，晶体学参数：a=1.625 9(3) nm，b=0.832 10(17) nm，c=2.031 1(4) nm，V=2.747 9(10) nm³，Z=4。配合物2属于正交晶系，空间群为Pca2₁，晶体学参数：a=1.674 36(15) nm，b=0.821 29(7) nm，c=2.048 01(19) nm，V=2.816 3(4) nm³，Z=4。在这2个配合物的阳离子中，金属原子分别与2个dmpzm中的4个N原子及1个NO₃^-中的2个O原子配位，形成略为畸变的八面体构型。配合物1和2的晶体中，NO₃^-的O原子与配体dmpzm中的甲基及亚甲基间存在的C-H…O氢键作用，从而形成了有趣的三维网状结构。此外，还研究了配合物1和2的荧光性质。     

Secondary bonding interactions in biomimetic [2Fe-2S] clusters

A series of synthetic [2Fe-2S] complexes with terminal thiophenolate ligands and tethered ether or thioether moieties has been prepared and investigated in order to provide models for the potential interaction of additional donor atoms with the Fe atoms in biological [2Fe-2S] clusters. X-ray crystal structures have been determined for six new complexes that feature appended Et (1(C)), OMe (1(O)), or SMe (1(S)) groups, or with a methylene group (2(C) ), an ether-O (2(O)), or an thioether-S (2(S)) linking two aryl groups. The latter two systems provide a constrained chelate arrangement that induces secondary bonding interactions with the ether-O and thioether-S, which is confirmed by density functional theory (DFT) calculations that also reveal significant spin density on those fifth donor atoms. Structural consequences of the secondary bonding interactions are analyzed in detail, and effects on the spectroscopic and electronic properties are probed by UV-vis, M?ssbauer, and (1)H NMR spectroscopy, as well by SQUID measurements and cyclic voltammetry. The potential relevance of the findings for biological [2Fe-2S] sites is considered.     

Abilities of different electron donors (D) to engage in a P···D noncovalent interaction

Previous work has documented the ability of the P atom to form a direct attractive noncovalent interaction with a N atom, based in large measure on the charge transfer from the N lone pair into the σ* antibonding orbital of the P-H that is turned away from the N atom. The present work considers whether other atoms, namely, O and S, can also participate as electron donors, and in which bonding environments. Also considered are the π-systems of multiply bonded C atoms. Unlike an earlier observation that the interaction is unaffected by the nature of the electron-acceptor atom, there is strong sensitivity to the donor. The P···D binding energy diminishes in the order D = NH(3) > H(2)CO > H(2)CS > H(2)O > H(2)S, different from the patterns observed in both H and halogen bonds. The P···D interactions are comparable to, and in some cases stronger than, the analogous H-bonds formed by HOH as proton donor. The carbon π systems form surprisingly strong P···D complexes, augmented by the back-donation from the P lone pair to the C-C π* antibond, which surpass the strengths of H-bonds, even some with HF as proton donor.     

Allosteric and Chelate Cooperativity in Divalent Crown Ether/Ammonium Complexes with Strong Binding Enhancement

A thorough thermodynamic analysis by isothermal titration calorimetry of allosteric and chelate cooperativity effects in divalent crown ether/ammonium complexes is combined with DFT calculations including implicit solvent on the one hand and large‐scale molecular dynamics simulations with explicit solvent molecules on the other. The complexes studied exhibit binding constants up to 2×10⁶ m ^?1 with large multivalent binding enhancements and thus strong chelate cooperativity effects. Slight structural changes in the spacers, that is, the exchange of two ether oxygen atoms by two isoelectronic methylene groups, cause significantly stronger binding and substantially increased chelate cooperativity. The analysis is complemented by the examination of solvent effects and allosteric cooperativity. Such a detailed understanding of the binding processes will help to efficiently design and construct larger supramolecular architectures with multiple multivalent building blocks.     

Structural variations across the lanthanide series of macrocyclic DOTA complexes: insights into the design of contrast agents for magnetic resonance imaging

It was early shown that the macrocyclic Ln(DOTA) complexes (DOTA = 1,4,7,10-tetra-azacyclododecane-N,N',N' ',N' "-tetraacetic acid) exists in solution as a mixture of two enantiomeric pairs of diastereoisomers differing in the ligand conformation, namely, square antiprismatic (SA) and twisted square antiprismatic (TSA) geometries, respectively. Later, extensive (1)H NMR investigations suggested that a coordination change may be superimposed on this conformational equilibrium involving two additional structures in which the metal ion possesses a coordination number of eight (CN 8). It was predicted that these two species, lacking the apical coordinated water molecule, would maintain the SA and TSA coordination geometries, and therefore, they have been labeled as SA' and TSA', respectively. In this work we report the X-ray solid-state crystal structure determination of six Ln(DOTA) complexes representative of all four coordination geometry typologies deduced from NMR solution studies. A distinctive structural feature that discriminates SA (and SA') and TSA (and TSA') structures is represented by the twist angle between the two square planes of the antiprism, the basal four nitrogen, and the apical four oxygen planes. [Ce(DOTA)(H(2)O)](-) displays a TSA structural typology with a twist angle of 25 degrees and a Ce-O(water) distance of 2.59 A. The SA-type structure has been found in the case of complexes with Pr(III), Nd(III), and Dy(III), where the twist angle is 39, 39, and 38 degrees, respectively, and the metal-water oxygen distance varies significantly (Pr-O(w) 2.529 A; Nd-O(w) 2.508 A; and Dy-O(w) 2.474 A). [Tm(DOTA)](-) displays a TSA'-type structure with a twist angle of 24 degrees. As compared with the TSA structure of the corresponding Ce(III) complex, the Tm(III) complex shows an overall marked shrinkage of all metal-nitrogen and metal-oxygen distances (ca. 0.2 A), which reflects the contraction of the metal ionic radius across the series but also the effect associated with the decrease of the CN from 9 to 8. In [Sc(DOTA)](-), the even smaller ionic radius of Sc(III) shifts the geometry of the coordination cage to the more compact SA' typology with a twist angle of 41 degrees, a value very similar to that found in the SA structures of lanthanide(III) ions with CN 9. Finally, an investigation was made into the hydration spheres of the complexes with SA and TSA geometries to account for the experimental evidence of a markedly different rate of water exchange for the two isomeric structures. This is of fundamental importance to the understanding of the corresponding Gd(III) complexes as MRI contrast agents.     

Molecular assembly directed by metal-aromatic interactions: control of the aggregation and photophysical properties of Zn-salen complexes by aromatic mercuration

There is widespread interest in non-covalent bonding and weak interactions, such as electrostatic interactions, hydrogen bonding, solvophobic/hydrophobic interactions, metal-metal interactions, and π-π stacking, to tune the molecular assembly of planar π-conjugated organic and inorganic molecules. Inspired by the roles of metal-aromatic interaction in biological systems, such as in ion channels and metalloproteins, herein, we report the first example of the use of Hg(2+) -aromatic interactions to selectively control the assembly and disassembly of zinc-salen complexes in aqueous media; moreover, this process exhibited significant "turn on" fluorescent properties. UV/Vis and fluorescence spectroscopic analysis of the titration of Hg(2+) ions versus complex ZnL(1) revealed that the higher binding affinity of Hg(2+) ions (compared to 13 other metal ions) was ascribed to specific interactions between the Hg(2+) ions and the phenyl rings of ZnL(1); this result was also confirmed by (1)H NMR spectroscopy and HRMS (ESI). Further evidence for this type of interaction was obtained from the reaction of small-molecule analogue L(1) with Hg(2+) ions, which demonstrates the proximity of the N-alkyl group to the aromatic protons during Hg(2+)-ion binding, which led to the consequential H/D exchange reaction with D(2) O. DFT modeling of such interactions between the Hg(2+) ions and the phenyl rings afforded calculated distances between the C and Hg atoms (2.29 ?) that were indicative of C-Hg bond-formation, under the direction of the N atom of the morpholine ring. The unusual coordination of Hg(2+) ions to the phenyl ring of the metallosalen complexes not only strengthened the binding ability but also increased the steric effect to promote the disassembly of ZnL(1) in aqueous media.     

Synthesis and Characterization of α-Hexadecyl-DOTA and its Gd(III) Chelate

Introduction Recent interest in polyazamacrocyclic paramagnetic Gd(III) chelates largely results form their clinical appli-cation for magnetic resonance imaging (MRI) contrast agents. The ligand DOTA (1,4,7,10-tetraazacyclodo- decane-N,N',N',N'-tetraacetic acid) forms one of the most thermodynamically stable and kinetically inert complexes with the trivalent lanthanide cations of any known chelate. These properties make Gd-DOTA one of the most effective and the safest MRI contrast …     

Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reductoisomerase complexes

We have obtained the single-crystal X-ray crystallographic structures of the bisphosphonates [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate, bound to the enzyme 1-deoxyxylulose-5-phosphate reductoisomerase (DXR, EC 1.1.1.267, also known as 2-C-methyl-d-erythritol-4-phosphate synthase), an important target for the development of antimalarial drugs. Our results indicate that both bisphosphonates bind into the fosmidomycin binding site. The aromatic groups are in a shallow hydrophobic pocket, and the phosphonate groups are involved in electrostatic interactions with Mg2+ or a cluster of carboxylic acid groups and lysine while the fosmidomycin phosphonate-binding site is occupied by a sulfate ion (as also observed in the DXR/NADP+ structure). The availability of these two new crystal structures opens up the possibility of the further development of bisphosphonates and related systems as DXR inhibitors and, potentially, as antiinfective agents.     

Spectral studies on the structure and monovalent cation binding to poly(1,3-propylene phosphate) — a synthetic analogue of natural teichoic acids

A poly(1,3-propylene phosphate), (PPP), which can be considered as a synthetic analogue of naturally occurring teichoic acids, has been studied with infrared spectroscopy. Infrared spectra of PPP in acidic and alkali metal forms have been analyzed in detail and the conclusions concerning intermolecular interactions between phosphate diester groups and the monovalent cation binding to PPP of a different degree of polymerization (n) have been drawn out. It has been shown that in anhydrous PPP, acidic groups are extensively hydrogen bonded. The process of association of phosphate diester groups is rather complex, especially in the samples of lowern. The role of H-bonds in some solution properties of high-molecular PPP samples has been discussed.     

含氟二羧酸和含氮配体与过渡金属(Ⅱ)配合物的合成、表征及晶体结构

水热法合成了5个新的配位聚合物:[Cd(TFSA)(2,2’-bpy)2]n(1),[Mn(HFGA)(phen)2]n(2),[Co(TFSA)(bpp)2(H2O)2]n(3),[Zn(TFSA)(bpp)2(H2O)2]n(4)和[Cu(HFGA)(phen)]n(5)(TFSA=四氟丁二酸,HFGA=六氟戊二酸,2,2’-bpy=2,2’-联吡啶,phen=1,10-邻菲啰啉,bpp=1,3-二吡啶基丙烷),通过X射线单晶衍射确定了配合物的晶体结构.配合物1和2具有相似的1D链结构,四氟丁二酸和六氟戊二酸以两个单齿羧基氧原子分别配位于Cd2+和Mn2+离子,2,2’-联吡啶和1,10-邻菲啰啉分别螯合配位于Cd2+和Mn2+离子.配合物3和4具有相似的1D链结构,1,3-二吡啶基丙烷以两个端基氮原子桥联金属离子,四氟丁二酸和六氟戊二酸分别以单齿方式配位.配合物5是具有{4.82}拓扑的2D网结构,六氟丁二酸配体通过单齿/双齿-桥联模式连接Cu2+离子.5个配合物均通过分子间弱作用进一步构筑成3D超分子结构.     

Formation kinetics and stability studies on the lanthanide complexes of 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid by capillary electrophoresis

In this study, the kinetic behaviors of four lanthanide ions, Sm(3+), Dy(3+), Yb(3+) and Lu(3+), when mixed with a polyazamacrocyclic chelating agent 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA), were investigated by capillary electrophoresis (CE) in the pH range of 2.0-6.0. At pH 2.0, the formation rate of DOTA-metal complex is extremely low as very little complex was detected after 5 days reaction, whereas almost no free DOTA was found in the mixture of metal ion and DOTA after 4 min at pH 6.0. The second-order kinetic association rate constants of the four lanthanide ions chelates at pH 4.2 were calculated as 1.44 x 10(-2) mM(-1)min(-1), 5.20 x 10(-2) mM(-1)min(-1), 4.56 x 10(-2) mM(-1)min(-1) and 4.54 x 10(-2) mM(-1)min(-1) at 25 degrees C with CE, respectively. In addition, the stability constants of the four lanthanide ions with DOTA were determined by CE at pH 3.0 where approximately 80-90% of the metal ions were associated with DOTA at 25 degrees C. The measured stability constants (log K(f)) of the four DOTA-metal complexes were 23.36, 23.93, 23.39 and 23.06, respectively, and correlated well with published data obtained by different methods. The percentage of metal ion bound with DOTA was evaluated as a function of reactant concentration in pH 6.0 buffer. After adding excess strong acid (0.1 M HCl) to each solution of DOTA-metal was formed at pH 6.0, no released DOTA was detected after 24 h; thus, dissociation of these lanthanide complexes did not occur under strongly acidic conditions. The Ln(DOTA)(-) species for the four DOTA-metal complexes were characterized by electrospray ionization-mass spectroscopy (ESI-MS), and the results correlated with proposed structures.     

Influence of Surface Hydrophobic Groups on the Adsorption of Proteins onto Nonporous Polymeric Particles with Immobilized Metal Ions

Iminodiacetic acid (IDA) and octyl moieties were covalently bound on nonporous particles, which were prepared from dispersion polymerization of methyl methacrylate and glycidyl methacrylate. After being charged with copper ions, the IDA-bound particles could specifically adsorb deoxyribonuclease I (DNase I) through the affinity interaction between protein and immobilized metal ion. A mixed-ligand (metal–chelate and octyl–bound) support was obtained after hydrophobic (octyl) groups were also introduced to the particle surface. The affinity adsorption of DNase I on the copper–IDA chelate was influenced by interaction between the protein and the bound octyl group. Both the affinity and the hydrophobic interactions could be well described by the Langmuir isotherms. The equilibrium adsorption constants were estimated separately to be 0.96 and 0.50 liter g⁻¹ for affinity and hydrophobic bindings, respectively. For binding on mixed-ligand support, the adsorption constant was 0.45 liter g⁻¹. It was evident that both affinity and hydrophobic interactions are involved in the adsorption of proteins onto mixed-ligand particles. Desorption of the inactive proteins from the support was possible by increasing the hydrophobicity of the solution.