My sincere thanks go to all the other faculty members in the Department of Chemistry for their help and encouragement and the non-teaching staff of the Department for their technical support. Structural characterization of complexes of L-methionine (Figure 2) and L-asparagine-derived ligands showed weak thioether and amide axial coordination with Cu(II), respectively.
Chiral recognition and resolution of amino alcohols through well defined interaction inside metallocavity
The small molecular weight and rigidity of the metal complexes can produce a structurally characterized host-guest adduct, which in turn can contribute to the understanding of the chiral recognition mechanism. Structural characterization of the bis-Cu(II) complexes supported by their solution and electrochemical studies revealed the interesting effect of ferrocene substitution on the axial coordination to the Cu(II) network and H-bonding in the crystal lattice.
Synthesis of the ligands and the Cu(II) complexes
Experimental Section .1 Solvents and Reagents
- Measurements
The IR and UV-vis spectra were recorded on a Perkin-Elmer Spectrum One FT-IR spectrophotometer with KBr disks in the range 4000-400 cm−1 and electronic spectra on a Perkin-Elmer Lambda 25 UV-vis spectrophotometer, respectively . Solid-state magnetic susceptibility of the complexes at room temperature was recorded using a Sherwood Scientific Magnetic balance MSB-1.
Synthesis of ligands
- Ferrocenylmethyl derivative of methionine [H(S-fMeth)] (1)
- Ferrocenylmethyl derivative of asparagine [H(S-fAsn)] (2)
- Ferrocenylmethyl derivative of serine [H(S-fSer)] (3)
- Ferrocenylmethyl derivative of threonine [H(S-fThr)] (4)
The hydrogen atoms were located where possible based on the difference Fourier maps and were isotropically refined. A cloudy solution was obtained, which was then acidified with dilute HCl and the pH of the solution was maintained between 5 and 7.
Syntheses of Complexes
Dark green crystals of 2a were grown by diffusion of diethyl ether into a methanol solution of the complex.
Result and discussion
- Synthesis and characterization of ligands and complexes
- Molecular structures
- H-Bonded Networks
- UV-visible absorption and EPR spectroscopy
- Electrochemistry
- Conclusion
The in-plane bond lengths for CuOcarboxylate are within the range of 1.92–1.94 Å observed for other amino acid or amino-derived ligand Cu(II) complexes.1 The in-plane bond lengths for CuNamine are longer at ∼2.01 apart from 2a compared to corresponding amino acid complexes Å).1. In 4a (Figure 2.6), the presence of polar water influenced the ferrocene units to move away from each other and methyl groups on top, forcing it to adopt a different arrangement containing channels (Figure 2.9). Due to the separation of hydrophobic and hydrophilic regions, the present complexes retain layered structure even when the amino acid is changed.
Experimental Section .1 Solvents and Reagents
In the previous chapter, we have explored the coordination chemistry of the ferrocenylmethyl derivatives of four amino acids with Cu(II) ion. We observed that two ligands organize around Cu(II) in a C2 symmetry such that both amino acid residues remain on the same side of the Cu(II) coordination plane (Scheme 3.1). Since our primary goal in this thesis was to create a chiral cavity around the binding site of the metal center for guest recognition, in this chapter we have used L-tyrosine derivative to form a chiral pocket around the fifth coordination site of Cu(II) (axial) and studied the guest binding preference with three monodentate heterocycles and water.
Synthesis
Recrystallization from MeOH by slow evaporation gave dark green rod-shaped crystals after three days. The complex was recrystallized by slow evaporation of the methanolic solution, and block-shaped crystals were obtained after four days. Green plate-like crystals of 4 were obtained by slow evaporation of the resulting solution after one week.
- Result and discussion
- Syntheses and Selected Properties
All the Cu(II) complexes were synthesized directly by reacting Cu(II), H2S-fTyr, base (LiOH or acetate anion), and guest molecule. All the complexes were characterized by FT-IR, elemental analysis and room temperature magnetic moments (experimental section). The IR spectra of the ligand and the complexes show strong and sharp asymmetric carboxylate stretches between 1580-1630 cm, 1 symmetric stretches ~1377 cm-1,1-2 The complexes are non-conducting, supporting the non-electrolytic nature of the complexes.
Synthesis of Cu(II) complexes
Molecular structures
In 1, Cu(II) is octahedrally coordinated by two bidentate (S-fTyr)1 ligands and two acetonitrile (Figure 3.1). One of the two axially coordinated acetonitrile is inside the cavity with a longer CuN (2.662(3) Å, Table 2) bond. The second acetonitrile molecule is bound to copper with relatively shorter CuN bond (2.537(3) Å, Table 2) between the two ferrocene units.
H-bonded networks
UV-visible absorption and EPR spectroscopy
Electrochemistry
Conclusions
In this chapter we intend to study the effect of chirality as well as the effect of co-ligand on the geometry and electronic properties of the complexes. If the chirality of the two ligands in the complex is different, two possible isomers can be formed. By changing one of the ligands to a bidentate ligand, we may gain some insight into their properties, as we will lose the cavity after changing the ligand ratio, and recently a similar complex has been found useful in DNA cleavage1. In this chapter, we have synthesized the ferrocenylmethyl derivative of L-leucine ligand as a new entry to compare the results with similar sets of previous complexes and prepared different types of Cu(II) complexes using pure and racemic form of the ligand and to last explored their coordination properties.
Experimental Section .1 Solvents and Reagents
- Measurements
In the previous two chapters, we first investigated the coordination chemistry of ferrocenylmethyl amino acid as a ligand towards Cu(II) using four different amino acids, followed by cavity formation with an L-tyrosine derivative. The electrical conductivity measurements of the solution were performed with a Eutech Instruments CON5/TDS 5 conductivity meter calibrated with 0.01 N KCl solution as a calibrant.
Synthesis of ligands .1 H(S-fLeu)
This was synthesized following the procedure described above for H(S-fLeu) using D-leucine instead of L-leucine. The solvent is evaporated and the resulting sticky mass is dissolved in water and acidified with solution. After filtration, it was thoroughly washed with water and MeOH and dried in a vacuum desiccator.
Syntheses of Complexes
The mixture was filtered after stirring for 2 hours, washed with cold MeOH and dried in vacuo. Crystal suitable for X-ray data collection was grown by slowly diffusing diethyl ether into a DMF solution. All geometric and intensity data for the crystals were collected at room temperature using a Bruker SMART APEX.
Result and discussion
- Synthesis and selected properties
- Structures of the bis-complexes
- Structures of crystal 3 and 4
- Electrochemical behavior of the complexes
- Conclusion
The isopropyl groups of the leucine ligand rotated away from the water molecule without forming a cavity. From the structure of 4 and 5, it is found that both molecules of asymmetric unit 5 are close to w. By varying the counterions, we tried to understand the binding preference of the cavity.
Experimental Section .1 Solvents and Reagents
The results presented in the previous chapters showed that the cavity with ferrocenylmethyl amino acid derivatives with Cu(II) forms a narrow cavity or none at all. The narrowness of the cavity formed by the tyrosine derivative limits the choice of guest molecules and we could not find a chiral guest suitable for the cavity. For this reason, we looked at complexes of the salicylaldehyde derivative of L-histidine previously reported by our group.1 The reported complex [FeIII2(OH)(LL-his)2(CH3COO)] had a cavity around the bridging acetate group on one side and two carboxylate and hydroxide aligned on the other side.
Synthesis
- K[Ni II 2 (L L-his ) 2 (CH 3 COO)] (2)
- Cs[Ni II 2 (L L-his ) 2 (CH 3 COO)] (3)
- NH 4 [Ni II 2 (L L-his ) 2 (CH 3 COO)] (4)
- Synthesis of [(R)-methylbenzylammonium)][Ni 2 (L L-his ) 2 (OAc) ] (5)
- Synthesis of [(S)-methylbenzylammonium][Ni 2 (L L-his ) 2 (OAc) ] (6)
Volume of the reaction mixture was reduced by rotary evaporation to ~10 mL and kept in refrigerator. Volume of the reaction mixture was reduced by rotary evaporation to ∼10 mL and kept refrigerated. The CHN analysis was in good agreement with the formula [(R)-methylbenzylammonium][Ni2(LL-his)2(OAc)]·6H2O. The mixture was stirred with heating in a water bath.
Results and Discussion
- Synthesis and Selected Properties
The SMART software was used for data acquisition and the SAINT software for data extraction. After the initial solution and refinement with SHELXL, the final refinements were performed on WinGX environment using SHELX-97.3a All non-hydrogen atoms were anisotropically refined. Where possible, the hydrogen atoms were located from the difference Fourier maps and were refined isotropically.
Synthesis of the binuclear complexes
Molecular structure and the cavity
- Alkali metal ion in the cavity
- Ammonium and alkyl ammonium cation in the cavity
- Solution behavior of the Host-Guest adducts
- Conclusion
Closer examination revealed that cation to one of the carbons of the ring is much shorter supporting the presence of interaction. The solution conductance measurements were performed in both methanol and DMF to ascertain the stability of the host–gas adducts. The other interesting aspect of the study is the observation of size-dependent effect of alkali metal ion on the lattice as well as on the geometry of the acetate bridge (Figure 5.4 A,B).
Structures of racemic amino alcohols used along with the noradrenaline and adrenaline
Experimental Section .1 Solvents and Reagents
- Measurements
In this chapter we have synthesized a mononuclear complex which behaves as a chiral monobasic acid and transforms into binuclear Ni(II) complexes in the presence of a base. Using amino alcohols as a base, we have been successful in separating the enantiomers of amino alcohols. Another reason for choosing amino alcohols is the presence of two different groups capable of H-bonding, namely the amine (ammonium after conversion) and the alcohol.
Syntheses of Complexes
- K[Ni 2 (L L-his ) 2 (OAc)](4)
Elemental analyzes were performed on a Carlo Erba 1108 and also using a Perkin-Elmer series II 2400 instrument. After stirring for 2 hours, the precipitated solid was filtered, washed with acetonitrile and dried in vacuo. It was prepared from 1 according to the procedure described for 2 using racemic 2-amino-1-propanol instead of 1-amino-2-propanol.
Quantitative estimation of 1-amino-2-propanol
Formation of the Schiff base
Estimation of enantiomeric separation through HPLC
- Isolation of Amine from reaction mixture of 1-2 (Extract 1 in Scheme 6. 3)
- Isolation of Amine from reaction mixture of 2-4 (Extract 2 in Scheme 6.3)
- Derivatization of chiral amines reacting with bezoyl chloride
Chiral amines were extracted from reaction mixture and degree of chiral separation was measured using HPLC using Chiralcel OD-H column attached with refractive index detector at a flow rate of 1mL/min. After stirring for 2-3 hours, the mixture was evaporated to dryness and was stirred with MeCN and filtered. Since the chiral column (Chiralcel OD-H) we used was not suitable for separating chiral amines, we derivatized the chiral amines to corresponding amide derivative before subjecting it to HPLC run.
Molecular Mechanics
Result and discussion
- Characterization of 1 and its behaviour as chiral monobasic acid
- Base induced mononuclear to binuclear transformation and chiral recognition
- Role of CH..... interaction in the recognition process
- Solution behaviour
- Recovery of the chiral guest
The PKa of the phenolic proton present in 1 was estimated to be ~6.6 (Figure 6.6), which is much lower than expected for the phenolic proton (range 8-10). These results highlight the strong nature of the H-bonds retained in DMF (partially in MeOH). This metathesis highlights the advantages of non-covalent interactions for recognition, allowing easy recovery of the guest.
Schematic representation of the sequence of reactions starting with monomer, its convertion to dinuclear cavity and eventual release of enantiomer after metathesis
Conclusion
The smaller size and stiffness of the resulting hosts allowed us for the first time to identify the molecular interactions responsible for recognition in a chiral cavity through structural characterization of the host-guest complexes. The flexibility of the design with regard to the choice of different amino acids and substitution in the aromatic ring used in the present method opens the possibility of recognition and effective separation of other amino alcohols. Structures of 2 and 3 also showed aligned carboxylates within the cavity, together with a solvent molecule, acting as an efficient receptor for amino alcohols compared to synthetically challenging organic designs.10 Isolation of acid 1 and its transformation were important because they provide a common route for relatively volatile chiral amines that are directly trapped in the cavity.
