Effect of Side Chain of α-Amino Acids and Esters on the Stability Constants for β-Cyclodextrin Complexes†

doi:10.7503/cjcu20160956

Abstract

Abstract:

For exploring effects of side chain R groups on binding strength of non-covalent complexes of β-cyclodextrin(β-CD) with α-amino acids and esters, a stoichiometry of β-CD with L-Norvaline(n-Val), L-Phenylalanine(Phe), L-Leucine(Leu) L-Aspartic acid(Asp), L-Aspartic acid-4-tert-butyl ester(Asp-4-t-butyl ester) and L-Aspartic acid-4-benzyl ester(Asp-4-benzyl ester) were mixed respectively and incubated at room temperature for 12 h to reach the equilibrium. In positive mode, electrospray ionization mass spectrometry(ESI MS) results indicated that β-CD could form non-covalent complexes with n-Val, Phe, Leu, Asp, Asp-4-t-butyl ester and Asp-4-benzyl ester, respectively. By comparison, two group competition reactions showed that the binding strength order were [β-CD∶Asp-4-benzyl ester+H]⁺>[β-CD∶Asp-4-t-butyl ester+H]⁺>[β-CD∶Asp+H]⁺ and [β-CD∶Phe+H]⁺>[β-CD∶Leu+H]⁺>[β-CD∶n-Val+H]⁺, respectively. The stability constants of the complexes of β-CD with α-amino acids and esters were determined via an improved mass spectrometric titration coupled with curve fitting methodology. The obtained lgK_st values were 1.81, 2.54, 3.14, 3.26, 3.36, 3.67 for [β-CD∶n-Val+H]⁺, [β-CD∶Asp+H]⁺, [β-CD∶Asp-4-t-butyl ester+H]⁺, [β-CD∶Asp-4-benzyl ester+H]⁺, [β-CD∶Leu+H]⁺ and [β-CD∶Phe+H]⁺, respectively. The obtained lgK_st values further confirmed competition reactions results. Because all α-amino acids or esters have the same C-termini(—COOH) and the N-termini(—NH₂), which are both hydrophilic, and different side chain R group. It can be concluded that the guest molecules were driven to approach β-CD by the hydrophobic force in the formation of the complexes in solution. Therefore, hydrophobic effect and polarity of the side chain R group can play an important role in the formation of the inclusion complexes. Moreover, the formed inclusion complexes can be stabilized by hydrogen-bonding interactions.

Key words: β-Cyclodextrin complex, Side chain of α-amino acid and ester, Stability constant, Electrospray ionization mass spectrometry

CLC Number:

O657.6

TrendMD:

HUANG Yandong, WU Ruofei, CHU Yanqiu, DING Chuanfan. Effect of Side Chain of α-Amino Acids and Esters on the Stability Constants for β-Cyclodextrin Complexes^†[J]. Chem. J. Chinese Universities, 2017, 38(5): 743.

Figures/Tables 8

Fig.1 Structures of α-amino acids and esters

Fig.2 Mass spectra for β-CD with amino acid and esters(A) n-Val; (B) Leu; (C) Phe; (D) Asp; (E) Asp-4-benzyl ester; (F) Asp-4-t-butyl ester.[β-CD]=[Amino acids or esters]=2.0×10-4 mol/L.

Fig.3 Relationship between [β-CD∶Leu+H]+ peak intensities and pH value(A) and declustering voltage(B)[β-CD]=[Leu]=2.0×10-4 mol/L.

Fig.4 Competitive reaction mass spectra for β-CD with amino acid and esters in groups(A) β-CD with n-Val, Leu, Phe;(B) β-CD with Asp, Asp-4-benzyl ester, Asp-4-t-butyl ester.[β-CD]=[Amino acids or esters]=2.0×10-4 mol/L.

Fig.5 CID curves of complexes of β-CD with amino acid and esters [β-CD]=[Amino acids or esters]=2.0×10-4 mol/L.

Fig.6 Linear fitting results of concentration and relative intensity of β-CD(A) Without internal standard; (B) with internal standard K5. [K5]=2.0×10-4 mol/L.

Fig.7 lg[Kst(I)] with variation in concentration of guest compounds(A) n-Val; (B)Leu; (C)Phe; (D)Asp; (E)Asp-4-benzyl ester; (F)Asp-4-t-butyl ester.[β-CD]=1.0×10-4 mol/L, [Internal standard K5]=2.0×10-4 mol/L.

Fig.8 Nonlinear fitting curves of [CD] and [G]t(A) n-Val; (B) Leu; (C) Phe; (D) Asp; (E) Asp-4-benzyl ester; (F) Asp-4-t-butyl ester.[β-CD]= 1.0×10-4 mol/L, [Internal standard K5]=2.0×10-4 mol/L.

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