Balbuena Research Group | Research | Ion Complexation Inside Macromolecules

Ion Complexation Inside Macromolecules

Dendrimers are envisioned as promising materials in many areas of science and technology with applications spanning design of drug delivery systems, light harvesting, electronic devices, and catalysis.^1-5 Poly(amido-amine) (PAMAM) dendrimers have proven successful template agents for several ions, metal atoms, and clusters, including Pt, Pd, Au, Ag, Cu.^6-11 As ion complexation precedes the formation of embedded metallic nanoclusters, a clear understanding of ion complexation and that of the influence of the factors that affect the complexation process – such as pH, counterion, ligand exchange, and charge transfer- are needed. Due to their own peculiarities each ionic complexation requires individual study; this fact hampers the understanding of currently known systems and the search for new precursor-dendrimer systems for metal nanoparticle synthesis.

We use classical MD and quantum DFT to analyze ion complexation inside dendrimers.

Figure 1 - a) Full-solvent MD final configuration A2 : Cu(II) is coordinated with two amide O, one tertiary N in EDA-core and one water O in equatorial position. Branch folding places one amide O in axial position (the other is occupied by one water O). For clarity, water molecules other than those in the first coordination sphere of the ion are not shown. b) 38-atom-fragment-Cu(II)-(H₂O)₃ closed DFT (optimized structure) : Cu(II) coordinates in a similar fashion to (a) except that the branch folding effect is obviously not reproduced; another water O substitutes the amide O of the dendrimer branch. Here the equatorial water and one of the axial waters form hydrogen bonds R’-CH2-(OH)---HOH---(OH)-CH2-R’ to both hydroxyl O atoms with lengths 2.12 Å and 1.99 Å respectively. These H-bonds may explain its enhanced stability compared to the “open” configuration. c) Full-solvent MD final configuration A3 : Cu(II) is coordinated to one amide O, one hydroxyl O and four water O. d) 38-atom-fragment-Cu(II)-(H₂O)₄ (optimized structure) : Coordination to one amide O, one hydroxyl O and two water O in equatorial plane and one water in axial position. One of the equatorial waters forms H-bond –dashed lines - as R’- C=O---HOH---(OH)-CH2-R at 1.81 Å (with carbonyl O) and 1.81 Å (with hydroxyl O). The fifth water is in quasi-axial position (bond distance larger than typical Cu-O axial bond distance) and forms H-bonds with one amide O at 1.78 Å and with the equatorial water at 1.60 Å.

Figure 2 - DFT optimized configurations. a) 38-atom-fragment -Cu(II): Cooperative effect of two amide O to the branching N is evident. b) 38-atom-fragment -Cu(II)-(H₂O)₆: Coordination to one amide O and five water O (3 equatorial and 2 axial). Water interacts with dendrimer atoms forming H-bonds: b1. R-CH2-(OH)---H, length: 1.83 Å. b2. The sixth water molecule sits in the second coordination shell and forms two hydrogen bonds –dashed lines- R’-C=O---HOH---(OH)-CH2-R in the adjacent branch at 1.81 Å (amide O) and 1.94 Å (hydroxyl O). c) 38-atom-fragment -Cu(II)-3H₂O open configuration: Coordination to one branching N, two amide O and one water O in equatorial plane and two water O in axial positions.

Figure 3 - Snapshots obtained after 600ps full-solvent MD trajectories. For clarity, water molecules beyond the ionic first coordination shell are not shown. a) Coordination of one Cu(II) to an amide O , an hydroxyl O and four water O and another Cu(II) to one amide O and five water O in the opposite part of the dendrimer that remains open. Two branches and their environment can at least hold one Cu(II). b) Coordination of both Cu(II) to two amide O, one hydroxyl O and three water O atoms. Again the flat configuration enables the attachment of two branches to each ion. The green atoms are Cl^-counterions.

This work highlights the importance of water in Cu(II) stabilization during ionic complexation to dendrimers and suggests that amide oxygen atoms and possibly in a lesser extent hydroxyl O atoms are likely to be the preferred coordination sites in EDA-core PAMAM -OH terminated dendrimers. In low generation dendrimers, coordination to amide oxygen and water oxygen seems to be dominant whereas coordination to the tertiary amine nitrogen in EDA-core is expected to be less frequently found.

Time evolution of the distance between the ion and the tertiary amine N atoms indicates that their residence times are very short, suggesting a weaker coordination of Cu(II) to that site than that to the amide O and water O atoms. The results from DFT calculations in dendrimer fragments, where branch folding effect is low, can provide insights on how the Cu(II) ion coordinates in the outer pockets of large generation dendrimers. These calculations show cooperativity between the branching tertiary amine nitrogen, amide oxygen atoms and water. However as branch mobility and folding are expected to be higher in large generation dendrimers, the latter statement needs to be taken with caution. MD simulations incorporating the full solvent effect reveal that both “closed” configurations where the dendrimer branches contribute to a “cage” effect, and “open” structures may be found. In gas phase, such closed configurations are found energetically favorable (by ~ 6 kcal/mol) to the open ones. Moreover, closed configurations are also found in structures showing two-ion attachments to G0-OH, where a strong participation of the dendrimer branches in complexation is observed.

Analyses of the various complexation structures of Cu(II) in various degrees of hydration indicates that combined effects of shorter and stronger bonds, H-bonding enhanced stability, and chelate formation can explain why Cu(II) hexahydrates tend to lose some of their coordination waters to bind to the dendrimer sites. Solvent screening effects can be accounted for obtaining a Cu(II)/dendrimer load ratio of at least 2:1 which is expected to be maximum as the ionic separation is approximately equal to the dendrimer size with branches flatly extended. We did not observe ion pairing between Cu⁺⁺ and Cl^- but the results cannot be extended to larger generation dendrimers where the available area for counterion contact is larger. Finally, this study expects to set a motivation for fundamental experimental research related to low generation dendrimers as potential generators of useful insights that can help explaining experimentally observed phenomena in dendrimers of larger generations; such valuable insights can be enhanced upon integration of theory and experiment.