Substituent effects on cation–π interactions: A quantitative study

Hunter, Christopher A.; Low, Caroline M. R.; Rotger, Carmen; Vinter, Jeremy G.; Zonta, Cristiano

doi:10.1073/pnas.072647899

Cited by 122 publications

(105 citation statements)

References 25 publications

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“…This renders the protein-DNA cation-interactions quite specific. This view is in agreement with the recent observations that the strength of the cation-interactions is very sensitive to the electron density on the face of the aromatic ring (38). In protein-ligand complexes, there are much fewer constraints, and amino side chains can come right above the aromatic cycles of the ligands, with the consequence that the cation-energy values are more similar for the four nucleic acid bases and that these interactions lose specificity.…”

Section: Conservation Of Cation-interactions In Protein Families-supporting

confidence: 80%

Probing the Energetic and Structural Role of Amino Acid/Nucleobase Cation-π Interactions in Protein-Ligand Complexes

Biot

Buisine

Kwasigroch

et al. 2002

Journal of Biological Chemistry

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X-ray structures of proteins bound to ligand molecules containing a nucleic acid base were systematically searched for cation-interactions between the base and a positively charged or partially charged side chain group located above it, using geometric criteria. Such interactions were found in 38% of the complexes and are thus even more frequent than -stacking interactions. They are moreover well conserved in families of related proteins. The overwhelming majority of cation-contacts involve Ade bases, as these constitute by far the most frequent ligand building block; Arg-Ade is the most frequent cation-pair. Ab initio energy calculations at MP2 level were performed on all recorded pairs. Though cation-interactions involving the net positive charge carried by Arg or Lys side chains are the most favorable energetically, those involving the partial positive charge of Asn and Gln side chain amino groups (sometimes referred to as amino-interactions) are favorable too, owing to the electron correlation energy contribution. Chains of cation-interactions with a nucleobase bound simultaneously to two charged groups or a charged group sandwiched between two aromatic moieties are found in several complexes. The systematic association of these motifs with specific ligand molecules in unrelated protein sequences raises the question of their role in protein-ligand structure, stability, and recognition.

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Section: Conservation Of Cation-interactions In Protein Families-supporting

confidence: 80%

Probing the Energetic and Structural Role of Amino Acid/Nucleobase Cation-π Interactions in Protein-Ligand Complexes

Biot

Buisine

Kwasigroch

et al. 2002

Journal of Biological Chemistry

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“…In our test set, even for large aromatics, viz. pyrene (12), [6]-cyclacene (13), and corannulene (14,15), the predicted E Li + values show good agreement with the calculated E M + . It means that even if induction dominates, a prediction of the interaction energy is possible by adding the contribution due to substituent effect on the interaction energy of the unsubstituted system.…”

Section: ■ Computational Detailssupporting

confidence: 71%

Accurate Prediction of Cation−π Interaction Energy Using Substituent Effects

Sayyed

Suresh

2012

J. Phys. Chem. A

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Substituent effects on cation-π interactions have been quantified using a variety of Φ-X···M(+) complexes where Φ, X, and M(+) are the π-system, substituent, and cation, respectively. The cation-π interaction energy, E(M(+)), showed a strong linear correlation with the molecular electrostatic potential (MESP) based measure of the substituent effect, ΔV(min) (the difference between the MESP minimum (V(min)) on the π-region of a substituted system and the corresponding unsubstituted system). This linear relationship is E(M(+)) = C(M(+))(ΔV(min)) + E(M(+))' where C(M(+)) is the reaction constant and E(M(+))' is the cation-π interaction energy of the unsubstituted complex. This relationship is similar to the Hammett equation and its first term yields the substituent contribution of the cation-π interaction energy. Further, a linear correlation between C(M(+))() and E(M(+))()' has been established, which facilitates the prediction of C(M(+)) for unknown cations. Thus, a prediction of E(M(+)) for any Φ-X···M(+) complex is achieved by knowing the values of E(M(+))' and ΔV(min). The generality of the equation is tested for a variety of cations (Li(+), Na(+), K(+), Mg(+), BeCl(+), MgCl(+), CaCl(+), TiCl(3)(+), CrCl(2)(+), NiCl(+), Cu(+), ZnCl(+), NH(4)(+), CH(3)NH(3)(+), N(CH(3))(4)(+), C(NH(2))(3)(+)), substituents (N(CH(3))(2), NH(2), OCH(3), CH(3), OH, H, SCH(3), SH, CCH, F, Cl, COOH, CHO, CF(3), CN, NO(2)), and a large number of π-systems. The tested systems also include multiple substituted π-systems, viz. ethylene, acetylene, hexa-1,3,5-triene, benzene, naphthalene, indole, pyrrole, phenylalanine, tryptophan, tyrosine, azulene, pyrene, [6]-cyclacene, and corannulene and found that E(M)(+) follows the additivity of substituent effects. Further, the substituent effects on cationic sandwich complexes of the type C(6)H(6)···M(+)···C(6)H(5)X have been assessed and found that E(M(+)) can be predicted with 97.7% accuracy using the values of E(M(+))' and ΔV(min). All the Φ-X···M(+) systems showed good agreement between the calculated and predicted E(M(+))() values, suggesting that the ΔV(min) approach to substituent effect is accurate and useful for predicting the interactive behavior of substituted π-systems with cations.

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“…5). The systems except DA = (NEt 2 ) 2 bpy have negative slopes, showing that the electron-rich aromatic ring of AA, Lπ, interacts with the Cu-DA moiety, Mπ, more strongly than the electron-deficient Lπ, so that the pyridine rings coordinated to metal ions can be regarded as comparable with the N-methylpyridinium ring in the systems by Hunter et al 34 and the perfluorobenzene ring in the systems by Cozzi and Siegel,7 in both of which the electrons are strongly withdrawn by the substituents. 30 These relationships indicate that DA in Cu(DA)(AA) except (NEt 2 ) 2 bpy with an electron-donating diethylamino group is π-deficient due to the Lewis acidity of Cu(II).…”

Section: Effects Of Substituents On the Aromatic-aromatic Interactionsmentioning

confidence: 97%

π–π Stacking assisted binding of aromatic amino acids by copper(ii)–aromatic diimine complexes. Effects of ring substituents on ternary complex stability

et al. 2007

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Ternary Cu(II) complexes containing an aromatic diimine (DA = di(2-pyridylmethyl)amine (dpa), 4,4'-disubstituted 2,2'-bipyridine (Y 2 bpy; Y = H (bpy), Me, Cl, N(Et) 2 , CONH 2 , or COOEt), or 2,2'-bipyrimidine) and an aromatic amino acid (AA = p-substituted L-phenylalanine (Xphe; X = H (phe), NH 2 , NO 2 , F, Cl, or Br), L-tyrosine, L-tryptophan (trp), or L-alanine) were studied by X-ray diffraction, spectroscopic, and potentiometric measurements.The structures IntroductionNoncovalent or weak interactions involving aromatic rings attract much attention for their importance in molecular recognition, stabilization of protein structures, and supramolecular architecture in chemistry and biology. [1][2][3][4] Studies on benzene and porphyrin dimers showed that the edge-to-face and offset face-to-face interactions between the aromatic molecules are more effective than the face-to-face interactions, 5,6 and a survey of protein structures revealed that the former type of interactions are most common for phenylalanine residues. 3 Cozzi and Siegel reported that the intensities of face-to-face interactions are influenced by ring substituents;electron-withdrawing groups strengthen the interactions while electron-donating groups weaken them. 7 On the other hand, cation-π interactions have been revealed for various systems including proteins, where the cationic groups of amino acid side chains such as guanidinium and ammonium groups were found to be located close to the aromatic rings of aromatic amino acid residues. 8Both gas-phase experiments and theoretical calculations indicated that alkali metal ions bind strongly to aromatic rings in the gas phase. 8,9 Metalation of porphyrin is known to enhance the π-π interaction between two porphyrin molecules due to intramolecular polarization of the metal ion and the porphyrin. 5,10 We have been studying aromatic ring stacking interactions in ternary Cu(II) and Pd(II) complexes, [M(DA)(AA)] (M = Cu(II) or Pd(II); DA = aromatic diimines such as 1,10-phenanthroline (phen); AA = aromatic amino acids such as L-tyrosine (tyr)); we found that metal-coordinated DA effectively stacks with the side chain aromatic ring of coordinated AA 11 and that the ring substituent in the interacting ring of AA has influence on the stacking. 11,12 While 2N1O-donor tripod-like ligands containing one pyridine and one phenol ring and a pendent indole ring were found to undergo only weak intramolecular indole-pyridine interactions in CH 3 CN, their Pd(II) complexes exhibited much stronger interactions as evidenced by the 1 H NMR upfield shifts due to the ring current effect and the methylene proton signals showing a fixed side chain conformation. 13 The adduct formation between planar Pt(II) complexes, Pt(DA)(L') (L' = 4 ethylenediamine or amino acids), and mononucleotides was revealed to be enthalpically driven mainly through stacking interactions by the relevant thermodynamic parameters 14 and decrease the electron density of the Pt(II) center as seen from and the downfield shift of the 195 Pt NMR s...

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Substituent effects on cation–π interactions: A quantitative study

Cited by 122 publications

References 25 publications

Probing the Energetic and Structural Role of Amino Acid/Nucleobase Cation-π Interactions in Protein-Ligand Complexes

Probing the Energetic and Structural Role of Amino Acid/Nucleobase Cation-π Interactions in Protein-Ligand Complexes

Accurate Prediction of Cation−π Interaction Energy Using Substituent Effects

π–π Stacking assisted binding of aromatic amino acids by copper(ii)–aromatic diimine complexes. Effects of ring substituents on ternary complex stability

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