Snežana D. Zarić

Metal Ligand Aromatic Cation–π Interactions in Metalloproteins: Ligands Coordinated to Metal Interact with Aromatic Residues

Cation-pi interactions between aromatic residues and cationic amino groups in side chains and have been recognized as noncovalent bonding interactions relevant for molecular recognition and for stabilization and definition of the native structure of proteins. We propose a novel type of cation-pi interaction in metalloproteins; namely interaction between ligands coordinated to a metal cation--which gain positive charge from the metal--and aromatic groups in amino acid side chains. Investigation of crystal structures of metalloproteins in the Protein Data Bank (PDB) has revealed that there exist quite a number of metalloproteins in which aromatic rings of phenylalanine, tyrosine, and tryptophan are situated close to a metal center interacting with coordinated ligands. Among these ligands are amino acids such as asparagine, aspartate, glutamate, histidine, and threonine, but also water and substrates like ethanol. These interactions play a role in the stability and conformation of metalloproteins, and in some cases may also be directly involved in the mechanism of enzymatic reactions, which occur at the metal center. For the enzyme superoxide dismutase, we used quantum chemical computation to calculate that Trp163 has an interaction energy of 10.09 kcal mol(-1) with the ligands coordinated to iron.

Evidence Based on Crystal Structures and Calculations of a C−H···π Interaction Between an Organic Moiety and a Chelate Ring in Transition Metal Complexes

Structural and computational evidence is given for a special type of C−H···π interaction where the C−H group interacts with the π-system of a six-membered chelate ring. An investigation of crystal structures shows that these interactions take place in quite a number of metal complexes, including organometallic compounds; in the CSD we found over 1200 structures with these interactions. These interactions exist in complexes of different metals and various chelate rings. DFT calculations on three model systems show that the energy of these interactions is about 1 kcal/mol. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

A reexamination of the propensities of amino acids towards a particular secondary structure: classification of amino acids based on their chemical structure

The correlation between the primary and secondary structures of proteins was analysed using a large data set from the Protein Data Bank. Clear preferences of amino acids towards certain secondary structures classify amino acids into four groups: α-helix preferrers, strand preferrers, turn and bend preferrers, and His and Cys (the latter two amino acids show no clear preference for any secondary structure). Amino acids in the same group have similar structural characteristics at their Cβ and Cγ atoms that predicts their preference for a particular secondary structure. All α-helix preferrers have neither polar heteroatoms on Cβ and Cγ atoms, nor branching or aromatic group on the Cβ atom. All strand preferrers have aromatic groups or branching groups on the Cβ atom. All turn and bend preferrers have a polar heteroatom on the Cβ or Cγ atoms or do not have a Cβ atom at all. These new rules could be helpful in making predictions about non-natural amino acids.

Stacking vs. CH–π interactions between chelate and aryl rings in crystal structures of square-planar transition metal complexes

The crystal structures of square-planar transition-metal complexes from the Cambridge Structural Database (CSD) with close contacts between planar chelate rings and aryl rings containing six carbon atoms (C6-aryl) were analyzed. Most of the chelate rings in these structures are fused with aromatic or other π-delocalized chelate rings. The results show that planar chelate rings can be involved in stacking and CH–π interactions with organic aryl rings. However, the number of stacking interactions is a few times larger than the number of CH–π interactions. The analysis also shows that in almost all cases CH–π interactions are formed only when stacking interactions are prevented by voluminous substituents. Hence, between planar chelate rings and C6-aryl rings stacking interactions are preferred to CH–π interactions.

What Are the Preferred Horizontal Displacements in Parallel Aromatic–Aromatic Interactions? Significant Interactions at Large Displacements

Aromatic–aromatic interactions are of great importance in numerous molecular systems, from biomolecules to molecular crystals, and play an important role in different fields ranging from molecular recognition and catalysis to transport. The majority of drug molecules contain aromatic rings and their interactions are crucial for their activity. It is important to understand the aromatic–aromatic interactions and to find out the preferred horizontal displacements (offsets) for parallel aromatic–aromatic interactions. Aromatic interactions have been extensively studied between two benzene molecules. Highlevel ab initio calculations showed two low-energy geometries of the benzene dimer. 4] In the first one, CH groups of one benzene molecule interact with the p system of the other, forming a CH–p interaction. The energy of the interaction is 2.84 kcal mol . In the other geometry, two benzene molecules are parallel with an offset (horizontal displacement) of 1.51 , forming a stacking interaction. The interaction energy is similar, namely, 2.73 kcal mol . In spite of extensive studies on benzene–benzene interactions, 3] no studies on stacking interactions with large horizontal displacement have been performed. Our recent results reveal that the parallel alignment on water–aromatic interactions can be significantly strong at large horizontal displacements. This prompted us to study benzene–benzene interactions at large horizontal displacements. Herein, we present our result on the interactions of two benzene molecules in the parallel orientation. Since analysis of the data in the crystal structures from the Cambridge Structural Database (CSD) enable the study of noncovalent interactions, 6] our analysis is based on crystal structures from the CSD. We also performed DFT and CCSD(T) calculations. To the best of our knowledge, this is the first study describing the significance of parallel aromatic–aromatic interactions at large offsets (horizontal displacements). The statistical study was based on the crystal structures archived in CSD (November 2010 release, version 5.32) A CSD search was performed using the ConQuest 1.13 program to extract all structures containing a benzene molecule and satisfying the following criteria: a) a crystallographic R factor below 10 %, b) error-free coordinates, c) normalized H-atom positions, and d) no polymer structures. The geometrical parameters used to search CSD, and to characterize the interactions between parallel benzene molecules, are displayed in Figure 1.

Cation–π interaction with transition-metal complex as cation

Abstract A novel type of cation–π interaction, where a transition-metal complex cation interacts with a π-system, is predicted here. The theoretical calculations on the [Co(NH3)6]3+–C6H6 system presented demonstrate that a transition-metal complex cation can interact strongly with π-systems. The bonding energy obtained with the B3LYP method is 31.34 kcal/mol. In the most stable structure, three NH3 groups from [Co(NH3)6]3+ interact with the π-system of benzene.

Parallel alignment of water and aryl rings—crystallographic and theoretical evidence for the interaction

Analysis of crystal structures from the Cambridge Structural Database (CSD) that involve close contact between water and aryl rings revealed the existance of conformations where the water molecule or one of its O-H bonds is parallel to the aromatic ring plane at distances typical for stacking interactions; attractive interaction energies obtained from ab initio calculations performed on model systems are significant (e.g.DeltaE(CCSD(T)) = -1.60 kcal mol(-1)) and consistent with the observed structures.

Surface modification of anatase nanoparticles with fused ring catecholate type ligands: a combined DFT and experimental study of optical properties

Surface modification of nanocrystalline TiO(2) particles (45 Å) with catecholate-type ligands consisting of an extended aromatic ring system, i.e., 2,3-dihydroxynaphthalene and anthrarobin, was found to alter the optical properties of the nanoparticles in a similar way to modification with catechol. The formation of inner-sphere charge-transfer (CT) complexes results in a red shift of the semiconductor absorption compared to unmodified nanocrystallites and the reduction of the band gap upon the increase of the electron delocalization on the inclusion of additional rings. The binding structures were investigated by FTIR spectroscopy. The investigated ligands have the optimal geometry for binding to surface Ti atoms, resulting in ring coordination complexes of catecholate type (binuclear bidentate binding-bridging) thus restoring the six-coordinated octahedral geometry of surface Ti atoms. From the Benesi-Hildebrand plot, stability constants in methanol/water = 90/10 solutions at pH 2 of the order 10(3) M(-1) have been determined. Quantum chemical calculations on model systems using density functional theory (DFT) were performed to obtain vibrational frequencies of charge transfer complexes, and the calculated values were compared with the experimental data.

Are C–H⋯O interactions linear? The case of aromatic CH donors

The angular distribution of the C–H⋯O interactions of aromatic C–H donors was studied by analyzing data in the Cambridge Structural Database (CSD) and by ab initio calculations. The analysis of the C–H⋯O interactions in the crystal structures from the CSD indicate that aromatic C–H donors do not show strong preference for linear contacts and that the preference depends on the type of the atom or group in the o-position to the interacting C–H group. Namely, the acceptor oxygen atom has possibility for simultaneous C–H⋯O interactions with the hydrogen atom in the o-position to the interacting C–H group. The C–H⋯O interactions of aromatic molecules with two hydrogen atoms in the o-positions do not show preference for linear contacts. Bifurcated interactions are observed in a substantial number of structures. Moreover, in the structures with a substituent in the o-position there is possibility for simultaneous interactions, depending on the nature of the substituent. The results of the ab initio calculations are in accord with the CSD data and show that the stabilization energy is larger for bifurcated than for linear interactions. The calculated energies at the MP2/cc-pVTZ level for linear C–H⋯O interactions of benzene with water, methanol, and acetone are 1.28, 1.47, 1.45 kcal mol−1; while for bifurcated interactions are 1.38, 1.63, and 1.70 kcal mol−1, respectively. Analysis of the data in the CSD and the ab initio calculations indicate that the vicinity of the other possible hydrogen donors in the aromatic molecules causes a small tendency for linear contact in the C–H⋯O interactions. The result that nonlinear interactions are not energetically disfavoured, because of the possibility for simultaneous interactions, can be very important for recognizing C–H⋯O interactions in biomolecules containing aromatic groups, like proteins.

Parallel Interactions at Large Horizontal Displacement in Pyridine–Pyridine and Benzene–Pyridine Dimers

A study of crystal structures from the Cambridge Structural Database (CSD) and DFT calculations reveals that parallel pyridine-pyridine and benzene-pyridine interactions at large horizontal displacements (offsets) can be important, similar to parallel benzene-benzene interactions. In the crystal structures from the CSD preferred parallel pyridine-pyridine interactions were observed at a large horizontal displacement (4.0-6.0 Å) and not at an offset of 1.5 Å with the lowest calculated energy. The calculated interaction energies for pyridine-pyridine and benzene-pyridine dimers at a large offset (4.5 Å) are about 2.2 and 2.1 kcal mol(-1), respectively. Substantial attraction at large offset values is a consequence of the balance between repulsion and dispersion. That is, dispersion at large offsets is reduced, however, repulsion is also reduced at large offsets, resulting in attractive interactions.