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Density functional studies of Cu2+ and Ni2+ binding to chitosan
Journal of Molecular Structure (Theochem) 499 (2000) 51–55 www.elsevier.nl/locate/theochem
Density functional studies of Cu 21 and Ni 21 binding to chitosan N.C. Braier*, R.A. Jishi Chemistry Division Code 6189, Naval Research Laboratory, Washington, DC 20375, USA Received 17 May 1999; accepted 7 July 1999
Abstract Density functional theory (DFT) calculations of the biopolymer chitosan interacting with transition metals Cu 21 and Ni 21 are presented. The DFT calculations explored divalent transition metal coordination structures by optimizing disaccharide–transition metal complexes. Results indicate that transition metal coordination to the chitosan biopolymer takes place in the vicinity of the glycosidic oxygen and includes interactions with nitrogen and hydroxyl oxygen atoms. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Density functional theory; Oligosaccharide; Chitosan binding site; Copper coordination
1. Introduction The function of metals in biological systems has been the focus of extensive research [1]. Bacterial, plant and mammalian systems use metals to achieve certain biological functions [2]. Of particular interest are the interactions between oligosaccharides and metals [3–5]. Oligosaccharides are involved in many biological processes [6–11]. The interactions of polysaccharide biopolymers can trigger transport across membranes [10,11] and mediate receptor binding [5]. Oligosaccharide–metal interactions can affect biofouling and bioremediation in marine environments [3]. Semiempirical methods have been used to study non-transition metal–saccharide coordination but calculations were limited to metals for which parameters have been developed [12,13]. Density functional theory (DFT) provides a new alternative in * Corresponding author. Tel.: 1 1-202-404-1687; fax: 1 1-202767-1716. E-mail address: [email protected] (N.C. Braier).
the study of metal–saccharide coordination. DFT methods do not require parametrization and can be used to study the interactions of oligosaccharides and other biomaterials with a variety of metals including transition metals [14]. DFT includes electronic correlations, the calculations are relatively fast and allow with the help of parallel computers, the study of systems much larger than those traditionally treated by other first-principles methods. In fact, DFT methods have already been used in the study of biological problems [15]. This paper reports a theoretical investigation on transition metal binding sites of the chitosan disaccharide. Chitosan is a very electronegative molecule. Its biopolymer forms stable complexes with transition metal cations even when the all-equatorial nature of the chitosan substituents makes binding unfavorable. Di-, tri-, and tetra-saccharides of chitosan in the presence of transition metals have been studied by potentiometry and tandem mass spectroscopy [16,17]. The potentiometry and tandem electrospray mass spectroscopy experiments have shown the formation of complexes between chitosan oligosaccharides
0166-1280/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S0166-128 0(99)00288-2
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N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
2. Theoretical procedures and method
Fig. 1. Structure of the chitosan disaccharide. Only heavy atoms are included in this figure.
and transition metals such as copper and nickel. The possible gas structure of these complexes is not known. The DFT calculations presented provide insight into the structure of oligosaccharide–transition metal coordination complexes.
We used DFT calculations to geometrically optimize the formation of complexes between disaccharides of chitosan and either copper (Cu 21) or nickel (Ni 21). Chitosan (Fig. 1) is an all equatorial molecule with b-1,4 interglycosidic linkages. The chitosan biopolymer has a primary amine in the equatorial carbon-2 position. The calculations were performed on the chitosan dimer. Initial structures were generated using the program CHARMM [18]. A combination of conjugate gradient and adopted basis Netwton–Raphson methods were used to minimize the initial structures. To make a complex, a transition metal (M 21) atom was ˚ of a given initial structure. DFT placed within 4.0 A optimizations probed several disaccharide conformations and different transition metal spatial locations. An optimal geometry was obtained by minimizing the maximum potential energy gradient to less than 0.005 a.u., which is close to the limit of accuracy of the numerical integration [19,20].
3. Results and discussion 3.1. Chitosan binding to copper
Fig. 2. Coordination of copper (Cu 21) to chitosan. The two lowest energy complexes are shown. (a) Shows Cu 21 interacting with O6, N2 and Og in structure A. (b) Shows Cu 21 interacting with O3, N2 and Og in structure B.
Evaluation of the DFT calculations indicates that coordination of copper to chitosan takes place in the vicinity of the interglycosidic linkage and includes the glycosidic oxygen (Og). Two possible coordination structures arise from the DFT calculations. Structure A features copper interacting with N2 of ring 1, O6 of ring 2 and Og (Fig. 2a). This structure was ˚ from lowest in relative energy. In A copper is 1.87 A ˚ from Og. These distances both N2 and O6 and 2.24 A indicate that copper binds to N2 and O6 and interacts but is not bound to Og. Copper-centered coordination angles are close to 908 and 1808 and copper’s rootmean-squared (rms) deviation from the plane formed ˚ . The coordination by atoms O6, Og and N2 is 0.02 A complex is therefore square planar. Average carbon–oxygen and carbon–nitrogen ˚ from the neutral bond distances decrease by 0.02 A uncoordinated disaccharide calculated distances. The overall shortening of bond distances is attributed to the redistribution of the positive charge over the
N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
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Table 1 Calculated properties of Cu 21 –chitosan coordinated complexes Property
˚) CuOg (A ˚) CuOg (A ˚) CuN (A ˚) COcplx (A ˚) COcrd (A ˚) CNcplx (A ˚) CNcrd (A /OCuN (8) /OgCuN (8) /OcuOg (8)
Structure A
B
1.87 2.24 1.87 1.39 1.45 1.42 1.47 177 88 94
1.88 2.51 1.89 1.38 1.43 1.40 1.46 145 83 80
divalent complex. However, the copper-coordinated N2 and O6 atoms carbon–heteroatom bond distances ˚ longer lengthen. The C2 –N2 bond in ring 1 is 0.06 A than the corresponding bond in ring 2 and the C6 –O6 ˚ longer than the corredistance in ring 2 is 0.03 A sponding C6 –O6 bond in ring 1 indicative of the strong copper–nitrogen and copper–oxygen interactions. Next in relative energy is the coordination structure B (Fig. 2b). In B copper interacts with O3 of ring 2, N2 of ring 1 and Og. Copper–disaccharide distances are ˚ to nitrogen, 1.89 A ˚ to the hydroxyl oxygen 1.88 A ˚ to the glycosidic oxygen. This (O3) and 2.51 A complex is not planar. Copper rms deviation from ˚ . Steric the plane formed by O3, Og and N2 is 0.22 A effects make the copper coordination structure in B Table 2 Calculated structural features for the Ni 21 –chitosan coordinated complexes Property
˚) NiOg (A ˚) NiOg (A ˚) NiN (A ˚) COcplx (A ˚) COcrd (A ˚) CNcplx (A ˚) CNcrd (A /ONi 21N (8) /OgNi 21N (8) /ONi 21Og (8)
Structure C
D
1.88 2.23 1.88 1.39 1.45 1.42 1.47 176 88 95
1.89 2.51 1.89 1.39 1.43 1.40 1.45 145 83 80
Fig. 3. Coordination of nickel (Ni 21) to chitosan. The two lowest energy complexes are shown. (a) Shows Ni 21 interacting with O6, N2 and Og in structure C. (b) Shows Ni 21 interacting with O3, N2 and Og in structure D.
22 kcal/mol higher than in energy than A. This steric hindrance arises from the proximity between the O3 ˚ in B versus a 3.75 A ˚ separation and N2 atoms, 3.59 A for the equivalent coordination atoms, O6 and N2, in A. The smaller coordination site in B cannot accommodate a planar coordination structure that maintains optimal copper interactions with Og, O6 and N2. Copper–nitrogen and copper–hydroxyl distances in ˚ rms deviation from correspondB are within a 0.02 A ing copper distances in coordination structure A. However, the distance between copper and the glyco˚ in B. Although sidic oxygen increases by 0.33 A complex B has the same type of interactions as A, the resulting coordination geometry—distorted tetragonal—and a weaker glycosidic oxygen–copper interaction explain the energy difference. The calculated structural properties for A and B are presented in Table 1.
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N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
3.2. Chitosan binding to nickel Nickel coordination to chitosan is most probable in the vicinity of the interglycosidic linkage. Calculated nickel–chitosan structures are similar to those obtained with copper. A summary of structural properties is presented in Table 2. Structure C (Fig. 3a) is lowest in relative energy. In C nickel interacts with the N2 atom of ring 1, the O6 ˚ from atom of ring 1 and the Og atom. Nickel is 1.88 A ˚ both N2 and O6 and 2.23 A from Og. Coordination distances indicate that nickel is chelated by N2 and O6 and also has a non-bonding interaction with Og. The coordination complex is square planar with Og – Ni–O6, Og –Ni–N2 and O6 –Ni–N coordination angles of 958, 888 and 1768, respectively. The nickel rms deviation from the plane formed by atoms N2, Og ˚ . In this positively charged complex, and O6 is 0.02 A average carbon–oxygen and carbon–nitrogen bond ˚ . Coordinated O6 distances decrease by about 0.01 A and N2 carbon–oxygen and carbon–nitrogen bond ˚, distances increase by at least 0.03 and 0.07 A respectively. Coordination complex D is closest to C in relative energy (Fig. 3b). Structure D is 15 kcal mol 21 higher in energy than D. In D nickel interacts with O3 of ring ˚ to 2, N2 of ring 1 and Og. Nickel distances are 1.89 A both nitrogen and the hydroxyl oxygen (O3) and ˚ to the glycosidic oxygen. Nickel has an rms 2.51 A ˚ from the O3, Og and N2 plane. The deviation of 0.22 A coordination site has a distorted tetragonal structure. Steric effects arise from proximity between the coor˚ in D dinated hydroxyl and nitrogen atoms, 3.59 A ˚ in C. The shorter distance drives the versus 3.79 A optimal copper interactions of the O3, Og and N2 plane and changes the coordination structure from square planar (in C) to distorted tetragonal. While coordinated nickel–amine and nickel–hydroxyl ˚ rms from oxygen distances in D are within 0.02 A the corresponding nickel distances in C, nickel is ˚ farther from the glycosidic oxygen in D thus 0.33 A weakening the Og –Ni 21 non-bonding interaction.
4. Final comments Using DFT we observed that transition metal binding to chitosan takes places in the vicinity of
glycosidic linkage. Our results also indicate that copper and nickel bind to chitosan in a similar manner. DFT calculations on both metals showed similar lower energy structures. All low energy structures included interactions with one of the amine nitrogens, N2 of ring 1, the glycosidic oxygen Og, and hydroxyl oxygens O6 or O3. Two general types of low energy coordination structures resulted from the calculations. Structures A and C represent one type of structure and structures B and D another type. The interacting atoms in the two types of structures differ only in the position of the hydroxyl atom, O6 versus O3. Measured metal–hydroxyl oxygen and metal–amine nitrogen distances in all four complexes ˚ rms difference but metal– are similar, within a 0.02 A ˚ glycosidic oxygen distances increase by over 0.30 A in structures B and D. Energetic differences between the two types of structures arise from the variation in size of the metal binding sites. Sites A and C are bigger and can better optimize interactions with all three coordinated atoms. These sites have a square planar geometry. Sites B and D are smaller. Specifically, the proximity between the hydroxyl oxygen and the nitrogen pushes the transition metal off the planar structure and into a distorted tetrahedral structure. The resulting geometry increases the glycosidic oxygen– metal distance and consequently, weakens this interaction. Chitosan is a chelating molecule. Copper/ nickel–nitrogen and copper/nickel–hydroxyl oxygen distances indicate that nitrogen and oxygen atoms (from a hydroxyl group) chelate these two transition metals. There is also an interaction between the transition metals and Og but this oxygen is farther than N2, ˚ farther in structures A and C and O6 or O3, about 0.4 A ˚ 0.8 A farther in structures B and D, and does not bind to copper. Gas phase mass spectroscopy experiments have been carried out on chitosan di-, tri- and tetrasaccharides [16]. In agreement with these calculations, experiments on the chitosan disaccharide indicate that one nitrogen atom is involved in the coordination. Fragmentation patterns of nickel–chitosan complexes suggest that nickel interacts with Og and O3. Structure D fits the mass spectroscopy data. In the case of copper coordination to chitosan, the experiments seem to indicate that copper interacts with a nitrogen, the glycosidic oxygen and the hydroxyl oxygen O1. DFT calculations did not suggest this interaction. For
N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
a structure to include these atoms, it would need to be in a higher energy regime as, for example, in a boat conformation. This type of conformation is possible in a mass spectroscopy experiment because energy is put into the gas phase molecule in order to fragment it. Higher energy conformations were beyond the scope of the present DFT calculations. The intermediate structures of non-equilibrium complexes can be studied in future calculations. Using DFT, we have investigated the interactions between transition metals and a model biopolymer. These types of studies applied to a variety of biomolecules can enhance our understanding and aid in the control of metal coordination in biological processes. Acknowledgements We would like to acknowledge helpful discussions with Dr J.H. Callahan, Dr C.T. White, Dr J.W. Mintmire and Dr L. Lou. R.A.J. gratefully acknowledges the U.S. Naval Research Laboratory for providing use of its computational resources. One of us (R.A.J.) acknowledges support from NSF under Grant HRD-9628526. N.C.B. acknowledges ONR support both directly under Grant N001499WX20257 and, indirectly through NRL, as well as computational support under the DOD HPCMP. References [1] G.L. Eichorn, L.G. Marzilli, Advances in Inorganic Chemistry, 4, Elsevier, New York, 1982.
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[2] T.W. Rademacher, R.B. Parekh, R.A. Dwek, Ann. Rev. Biochem. 57 (1988) 785. [3] G.G. Geesey, L. Jang, Microbial Mineral Recovery, McGrawHill, New York, 1990, p. 223. [4] W.J. Cook, C.E. Bugg, Metal–Ligand Interactions in Organic Chemistry and Biochemistry, Reidel, Dordrecht, 1977, pp. 231–256, Part 2. [5] D.M. Whitfield, S. Stojkovski, B. Sarkar, Coord. Chem. Rev. 122 (1993) 171. [6] K.-A. Karlsson, Ann. Rev. Biochem. 58 (1989) 309. [7] N. Sharon, H. Lis, Science 246 (1989) 227. [8] G.W. Hart, R.S. Altiwanger, Trends Biochem. Sci. 13 (1988) 380. [9] Y. Sugiura, K. Nomoto, Struct. Bond. 58 (1984) 109. [10] R.H. Holm, J.M. Berg, Pure Appl. Chem. 56 (1984) 1645. [11] P.F. Predki, D.M. Whitfeld, B. Sarkar, Biochem. J. 281 (1992) 835. [12] A. Staempfli, Z. Zhou, J.A. Leary, J. Org. Chem. 57 (1992) 3590. [13] Y.-J. Zheng, A. Staempfli, J.A. Leary, J. Am. Soc. Mass Spectrom. 4 (1993) 943. [14] Y.-J. Zheng, R.L. Ornstein, J.A. Leary, J. Mol. Struct. (Theochem) 389 (1997) 233. [15] J.K. Labanowsky, J.W. Andzelm, Density Functional Methods in Chemistry, Springer, New York, 1991. [16] M. Shahgoli, J.H. Callahan, B.J. Rappoli, D. Rowley, J. Mass. Spectrom. 32 (1997) 1080. [17] M. Shahgoli, J.H. Callahan, B.J. Rappoli, D. Rowley, N.C. Braier, R.A. Jishi, personal communication, 1999. [18] B.R. Brooks, R.E. Bruccoleri, B.D. Olafson, D.J. States, S. Swaminathan, M. Karplus, J. Comput. Chem. 4 (1983) 187, CHARMM version used is c24b2. [19] L. Lou, P. Nordlanker, R.E. Smalley, J. Chem. Phys. 97 (1992) 1858. [20] S.H. Vosko, L. Wilk, M. Nussair, Can. J. Phys. 58 (1980) 1200.
Density functional studies of Cu 21 and Ni 21 binding to chitosan N.C. Braier*, R.A. Jishi Chemistry Division Code 6189, Naval Research Laboratory, Washington, DC 20375, USA Received 17 May 1999; accepted 7 July 1999
Abstract Density functional theory (DFT) calculations of the biopolymer chitosan interacting with transition metals Cu 21 and Ni 21 are presented. The DFT calculations explored divalent transition metal coordination structures by optimizing disaccharide–transition metal complexes. Results indicate that transition metal coordination to the chitosan biopolymer takes place in the vicinity of the glycosidic oxygen and includes interactions with nitrogen and hydroxyl oxygen atoms. q 2000 Elsevier Science B.V. All rights reserved. Keywords: Density functional theory; Oligosaccharide; Chitosan binding site; Copper coordination
1. Introduction The function of metals in biological systems has been the focus of extensive research [1]. Bacterial, plant and mammalian systems use metals to achieve certain biological functions [2]. Of particular interest are the interactions between oligosaccharides and metals [3–5]. Oligosaccharides are involved in many biological processes [6–11]. The interactions of polysaccharide biopolymers can trigger transport across membranes [10,11] and mediate receptor binding [5]. Oligosaccharide–metal interactions can affect biofouling and bioremediation in marine environments [3]. Semiempirical methods have been used to study non-transition metal–saccharide coordination but calculations were limited to metals for which parameters have been developed [12,13]. Density functional theory (DFT) provides a new alternative in * Corresponding author. Tel.: 1 1-202-404-1687; fax: 1 1-202767-1716. E-mail address: [email protected] (N.C. Braier).
the study of metal–saccharide coordination. DFT methods do not require parametrization and can be used to study the interactions of oligosaccharides and other biomaterials with a variety of metals including transition metals [14]. DFT includes electronic correlations, the calculations are relatively fast and allow with the help of parallel computers, the study of systems much larger than those traditionally treated by other first-principles methods. In fact, DFT methods have already been used in the study of biological problems [15]. This paper reports a theoretical investigation on transition metal binding sites of the chitosan disaccharide. Chitosan is a very electronegative molecule. Its biopolymer forms stable complexes with transition metal cations even when the all-equatorial nature of the chitosan substituents makes binding unfavorable. Di-, tri-, and tetra-saccharides of chitosan in the presence of transition metals have been studied by potentiometry and tandem mass spectroscopy [16,17]. The potentiometry and tandem electrospray mass spectroscopy experiments have shown the formation of complexes between chitosan oligosaccharides
0166-1280/00/$ - see front matter q 2000 Elsevier Science B.V. All rights reserved. PII: S0166-128 0(99)00288-2
52
N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
2. Theoretical procedures and method
Fig. 1. Structure of the chitosan disaccharide. Only heavy atoms are included in this figure.
and transition metals such as copper and nickel. The possible gas structure of these complexes is not known. The DFT calculations presented provide insight into the structure of oligosaccharide–transition metal coordination complexes.
We used DFT calculations to geometrically optimize the formation of complexes between disaccharides of chitosan and either copper (Cu 21) or nickel (Ni 21). Chitosan (Fig. 1) is an all equatorial molecule with b-1,4 interglycosidic linkages. The chitosan biopolymer has a primary amine in the equatorial carbon-2 position. The calculations were performed on the chitosan dimer. Initial structures were generated using the program CHARMM [18]. A combination of conjugate gradient and adopted basis Netwton–Raphson methods were used to minimize the initial structures. To make a complex, a transition metal (M 21) atom was ˚ of a given initial structure. DFT placed within 4.0 A optimizations probed several disaccharide conformations and different transition metal spatial locations. An optimal geometry was obtained by minimizing the maximum potential energy gradient to less than 0.005 a.u., which is close to the limit of accuracy of the numerical integration [19,20].
3. Results and discussion 3.1. Chitosan binding to copper
Fig. 2. Coordination of copper (Cu 21) to chitosan. The two lowest energy complexes are shown. (a) Shows Cu 21 interacting with O6, N2 and Og in structure A. (b) Shows Cu 21 interacting with O3, N2 and Og in structure B.
Evaluation of the DFT calculations indicates that coordination of copper to chitosan takes place in the vicinity of the interglycosidic linkage and includes the glycosidic oxygen (Og). Two possible coordination structures arise from the DFT calculations. Structure A features copper interacting with N2 of ring 1, O6 of ring 2 and Og (Fig. 2a). This structure was ˚ from lowest in relative energy. In A copper is 1.87 A ˚ from Og. These distances both N2 and O6 and 2.24 A indicate that copper binds to N2 and O6 and interacts but is not bound to Og. Copper-centered coordination angles are close to 908 and 1808 and copper’s rootmean-squared (rms) deviation from the plane formed ˚ . The coordination by atoms O6, Og and N2 is 0.02 A complex is therefore square planar. Average carbon–oxygen and carbon–nitrogen ˚ from the neutral bond distances decrease by 0.02 A uncoordinated disaccharide calculated distances. The overall shortening of bond distances is attributed to the redistribution of the positive charge over the
N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
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Table 1 Calculated properties of Cu 21 –chitosan coordinated complexes Property
˚) CuOg (A ˚) CuOg (A ˚) CuN (A ˚) COcplx (A ˚) COcrd (A ˚) CNcplx (A ˚) CNcrd (A /OCuN (8) /OgCuN (8) /OcuOg (8)
Structure A
B
1.87 2.24 1.87 1.39 1.45 1.42 1.47 177 88 94
1.88 2.51 1.89 1.38 1.43 1.40 1.46 145 83 80
divalent complex. However, the copper-coordinated N2 and O6 atoms carbon–heteroatom bond distances ˚ longer lengthen. The C2 –N2 bond in ring 1 is 0.06 A than the corresponding bond in ring 2 and the C6 –O6 ˚ longer than the corredistance in ring 2 is 0.03 A sponding C6 –O6 bond in ring 1 indicative of the strong copper–nitrogen and copper–oxygen interactions. Next in relative energy is the coordination structure B (Fig. 2b). In B copper interacts with O3 of ring 2, N2 of ring 1 and Og. Copper–disaccharide distances are ˚ to nitrogen, 1.89 A ˚ to the hydroxyl oxygen 1.88 A ˚ to the glycosidic oxygen. This (O3) and 2.51 A complex is not planar. Copper rms deviation from ˚ . Steric the plane formed by O3, Og and N2 is 0.22 A effects make the copper coordination structure in B Table 2 Calculated structural features for the Ni 21 –chitosan coordinated complexes Property
˚) NiOg (A ˚) NiOg (A ˚) NiN (A ˚) COcplx (A ˚) COcrd (A ˚) CNcplx (A ˚) CNcrd (A /ONi 21N (8) /OgNi 21N (8) /ONi 21Og (8)
Structure C
D
1.88 2.23 1.88 1.39 1.45 1.42 1.47 176 88 95
1.89 2.51 1.89 1.39 1.43 1.40 1.45 145 83 80
Fig. 3. Coordination of nickel (Ni 21) to chitosan. The two lowest energy complexes are shown. (a) Shows Ni 21 interacting with O6, N2 and Og in structure C. (b) Shows Ni 21 interacting with O3, N2 and Og in structure D.
22 kcal/mol higher than in energy than A. This steric hindrance arises from the proximity between the O3 ˚ in B versus a 3.75 A ˚ separation and N2 atoms, 3.59 A for the equivalent coordination atoms, O6 and N2, in A. The smaller coordination site in B cannot accommodate a planar coordination structure that maintains optimal copper interactions with Og, O6 and N2. Copper–nitrogen and copper–hydroxyl distances in ˚ rms deviation from correspondB are within a 0.02 A ing copper distances in coordination structure A. However, the distance between copper and the glyco˚ in B. Although sidic oxygen increases by 0.33 A complex B has the same type of interactions as A, the resulting coordination geometry—distorted tetragonal—and a weaker glycosidic oxygen–copper interaction explain the energy difference. The calculated structural properties for A and B are presented in Table 1.
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3.2. Chitosan binding to nickel Nickel coordination to chitosan is most probable in the vicinity of the interglycosidic linkage. Calculated nickel–chitosan structures are similar to those obtained with copper. A summary of structural properties is presented in Table 2. Structure C (Fig. 3a) is lowest in relative energy. In C nickel interacts with the N2 atom of ring 1, the O6 ˚ from atom of ring 1 and the Og atom. Nickel is 1.88 A ˚ both N2 and O6 and 2.23 A from Og. Coordination distances indicate that nickel is chelated by N2 and O6 and also has a non-bonding interaction with Og. The coordination complex is square planar with Og – Ni–O6, Og –Ni–N2 and O6 –Ni–N coordination angles of 958, 888 and 1768, respectively. The nickel rms deviation from the plane formed by atoms N2, Og ˚ . In this positively charged complex, and O6 is 0.02 A average carbon–oxygen and carbon–nitrogen bond ˚ . Coordinated O6 distances decrease by about 0.01 A and N2 carbon–oxygen and carbon–nitrogen bond ˚, distances increase by at least 0.03 and 0.07 A respectively. Coordination complex D is closest to C in relative energy (Fig. 3b). Structure D is 15 kcal mol 21 higher in energy than D. In D nickel interacts with O3 of ring ˚ to 2, N2 of ring 1 and Og. Nickel distances are 1.89 A both nitrogen and the hydroxyl oxygen (O3) and ˚ to the glycosidic oxygen. Nickel has an rms 2.51 A ˚ from the O3, Og and N2 plane. The deviation of 0.22 A coordination site has a distorted tetragonal structure. Steric effects arise from proximity between the coor˚ in D dinated hydroxyl and nitrogen atoms, 3.59 A ˚ in C. The shorter distance drives the versus 3.79 A optimal copper interactions of the O3, Og and N2 plane and changes the coordination structure from square planar (in C) to distorted tetragonal. While coordinated nickel–amine and nickel–hydroxyl ˚ rms from oxygen distances in D are within 0.02 A the corresponding nickel distances in C, nickel is ˚ farther from the glycosidic oxygen in D thus 0.33 A weakening the Og –Ni 21 non-bonding interaction.
4. Final comments Using DFT we observed that transition metal binding to chitosan takes places in the vicinity of
glycosidic linkage. Our results also indicate that copper and nickel bind to chitosan in a similar manner. DFT calculations on both metals showed similar lower energy structures. All low energy structures included interactions with one of the amine nitrogens, N2 of ring 1, the glycosidic oxygen Og, and hydroxyl oxygens O6 or O3. Two general types of low energy coordination structures resulted from the calculations. Structures A and C represent one type of structure and structures B and D another type. The interacting atoms in the two types of structures differ only in the position of the hydroxyl atom, O6 versus O3. Measured metal–hydroxyl oxygen and metal–amine nitrogen distances in all four complexes ˚ rms difference but metal– are similar, within a 0.02 A ˚ glycosidic oxygen distances increase by over 0.30 A in structures B and D. Energetic differences between the two types of structures arise from the variation in size of the metal binding sites. Sites A and C are bigger and can better optimize interactions with all three coordinated atoms. These sites have a square planar geometry. Sites B and D are smaller. Specifically, the proximity between the hydroxyl oxygen and the nitrogen pushes the transition metal off the planar structure and into a distorted tetrahedral structure. The resulting geometry increases the glycosidic oxygen– metal distance and consequently, weakens this interaction. Chitosan is a chelating molecule. Copper/ nickel–nitrogen and copper/nickel–hydroxyl oxygen distances indicate that nitrogen and oxygen atoms (from a hydroxyl group) chelate these two transition metals. There is also an interaction between the transition metals and Og but this oxygen is farther than N2, ˚ farther in structures A and C and O6 or O3, about 0.4 A ˚ 0.8 A farther in structures B and D, and does not bind to copper. Gas phase mass spectroscopy experiments have been carried out on chitosan di-, tri- and tetrasaccharides [16]. In agreement with these calculations, experiments on the chitosan disaccharide indicate that one nitrogen atom is involved in the coordination. Fragmentation patterns of nickel–chitosan complexes suggest that nickel interacts with Og and O3. Structure D fits the mass spectroscopy data. In the case of copper coordination to chitosan, the experiments seem to indicate that copper interacts with a nitrogen, the glycosidic oxygen and the hydroxyl oxygen O1. DFT calculations did not suggest this interaction. For
N.C. Braier, R.A. Jishi / Journal of Molecular Structure (Theochem) 499 (2000) 51–55
a structure to include these atoms, it would need to be in a higher energy regime as, for example, in a boat conformation. This type of conformation is possible in a mass spectroscopy experiment because energy is put into the gas phase molecule in order to fragment it. Higher energy conformations were beyond the scope of the present DFT calculations. The intermediate structures of non-equilibrium complexes can be studied in future calculations. Using DFT, we have investigated the interactions between transition metals and a model biopolymer. These types of studies applied to a variety of biomolecules can enhance our understanding and aid in the control of metal coordination in biological processes. Acknowledgements We would like to acknowledge helpful discussions with Dr J.H. Callahan, Dr C.T. White, Dr J.W. Mintmire and Dr L. Lou. R.A.J. gratefully acknowledges the U.S. Naval Research Laboratory for providing use of its computational resources. One of us (R.A.J.) acknowledges support from NSF under Grant HRD-9628526. N.C.B. acknowledges ONR support both directly under Grant N001499WX20257 and, indirectly through NRL, as well as computational support under the DOD HPCMP. References [1] G.L. Eichorn, L.G. Marzilli, Advances in Inorganic Chemistry, 4, Elsevier, New York, 1982.
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