Dragan B. Ninković

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.

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.

Stacking of Benzene with Metal Chelates: Calculated CCSD(T)/CBS Interaction Energies and Potential-Energy Curves

Accurate values for the energies of stacking interactions of nickel- and copper-based six-membered chelate rings with benzene are calculated at the CCSD(T)/CBS level. The results show that calculations made at the ωB97xD/def2-TZVP level are in excellent agreement with CCSD(T)/CBS values. The energies of [Cu(C3H3O2)(HCO2)] and [Ni(C3H3O2)(HCO2)] chelates stacking with benzene are -6.39 and -4.77 kcal mol(-1), respectively. Understanding these interactions might be important for materials with properties that are dependent on stacking interactions.

Aliphatic–aromatic stacking interactions in cyclohexane–benzene are stronger than aromatic–aromatic interaction in the benzene dimer

Stacking interactions between cyclohexane and benzene were studied in crystal structures from the Cambridge Structural Database and by ab initio calculations. Calculated at the very accurate CCSD(T)/CBS level of theory, the cyclohexane-benzene interaction energy is -3.27 kcal mol-1, which is significantly stronger than the interaction in the benzene dimer (-2.84 kcal mol-1) indicating the importance of aliphatic-aromatic interactions.

Stacking of Metal Chelates with Benzene: Can Dispersion‐Corrected DFT Be Used to Calculate Organic–Inorganic Stacking?

CCSD(T)/CBS energies for stacking of nickel and copper chelates are calculated and used as benchmark data for evaluating the performance of dispersion-corrected density functionals for calculating the interaction energies. The best functionals for modeling the stacking of benzene with the nickel chelate are M06HF-D3 with the def2-TZVP basis set, and B3LYP-D3 with either def2-TZVP or aug-cc-pVDZ basis set, whereas for copper chelate the PBE0-D3 with def2-TZVP basis set yielded the best results. M06L-D3 with aug-cc-pVDZ gives satisfying results for both chelates. Most of the tested dispersion-corrected density functionals do not reproduce the benchmark data for stacking of benzene with both nickel (no unpaired electrons) and copper chelate (one unpaired electron), whereas a number of these functionals perform well for interactions of organic molecules.

Geometries of stacking interactions between phenanthroline ligands in crystal structures of square-planar metal complexes

Stacking interactions of phenanthroline square-planar complexes in crystal structures were studied by analyzing data from the Cambridge Structural Database. In most of the crystal structures, two phenanthroline complexes were oriented “head to tail.” Phenanthroline complexes show a wide range of overlap geometries in stacking interactions, while short metal–metal distances were not observed. Stacking chains with alternating overlaps were the predominant type of packing in the crystal structures.

The influence of water molecule coordination onto the water–aromatic interaction. Strong interactions of water coordinating to a metal ion

The interactions between water molecules (non-coordinating and coordinating) and aromatic rings were studied by analyzing data in the Cambridge Structural Database and by quantum chemical calculations. The results show the influence of water coordination to a metal ion; interactions of coordinating water are stronger. The MP2/def2-QZVP interaction energies of non-coordinating water and neutral aqua complexes [ScCl3(H2O)3], [ZnCl2(H2O)4], [CdCl2(H2O)4], and [ZnCl2(H2O)2] with benzene molecule are −3.36, −5.10, −5.43, −6.86, and −5.14 kcal mol−1, respectively. Interactions of charged aqua complexes [ZnCl(H2O)5]+ and [Zn(H2O)6]2+ are stronger, −9.69 and −13.96 kcal mol−1, respectively. The calculations also reveal strong long-range interactions: at the distance of 3.0 A the interaction energies of neutral complexes are in the range of −4.11 to −4.91 kcal mol−1, while interaction energies of charged complexes are −6.37 and −10.76 kcal mol−1.

Influence of supramolecular structures in crystals on parallel stacking interactions between pyridine molecules

Parallel stacking interactions between pyridines in crystal structures and the influence of hydrogen bonding and supramolecular structures in crystals on the geometries of interactions were studied by analyzing data from the Cambridge Structural Database (CSD). In the CSD 66 contacts of pyridines have a parallel orientation of molecules and most of these pyridines simultaneously form hydrogen bonds (44 contacts). The geometries of stacked pyridines observed in crystal structures were compared with the geometries obtained by calculations and explained by supramolecular structures in crystals. The results show that the mean perpendicular distance (R) between pyridine rings with (3.48 Å) and without hydrogen bonds (3.62 Å) is larger than that calculated, because of the influence of supramolecular structures in crystals. The pyridines with hydrogen bonds show a pronounced preference for offsets of 1.25-1.75 Å, close to the position of the calculated minimum (1.80 Å). However, stacking interactions of pyridines without hydrogen bonds do not adopt values at or close to that of the calculated offset. This is because stacking interactions of pyridines without hydrogen bonds are less strong, and they are more susceptible to the influence of supramolecular structures in crystals. These results show that hydrogen bonding and supramolecular structures have an important influence on the geometries of stacked pyridines in crystals.

Carbon-hydrogen bond activation by a titanium neopentylidene complex

Abstract The titanium neopentylidene complex (PNP)Ti=CHtBu(CH2tBu), PNP=N[2-PiPr2-4-methylphenyl]2−, can activate both sp2 and sp3 C–H bonds under mild conditions. In this work, we studied the reaction mechanism of this complex with benzene and methane using modern density functional theory, specifically the ωB97XD functional which contains long-range exchange and dispersion corrections. The mechanism of the reaction is similar to that computed previously in the literature, but we describe a new conformer that is both more stable and kinetically more reactive. The four-step mechanism is very similar for both benzene and methane. However, the highest energy barriers differ; for methane, it is the last step, which elucidates the inertness of that reactant. In addition, the hydrogen exchange between alkyl and alkylidene ligands in methane’s product was studied by two different mechanisms: tautomerization to form (PNP)TiCHtBu(=CH2) and reverse C–H activation to form (PNP)Ti≡CtBu(CH3). The feasibility of the tautomerization, through a preliminary, accessible isomerization, suggests that these systems can be used to explore the reactivity of terminal methylidenes. Finally, methodological considerations are also discussed, as the importance of including the dispersion in the density functionals was determined by comparing several functionals. This comparison has shown that the dispersion is critical for accurate modeling, especially in the stability of the unsaturated intermediate; this has been neglected in previous studies.

Methane Activations by Titanium Neopentylidene Complexes: Electronic Resilience and Steric Control

The titanium neopentylidene complex (PNP)Ti═CHtBu(CH2tBu) (PNP = N[2-PiPr2-4-methylphenyl]2-) is capable of activating both sp2 and sp3 C-H bonds under mild conditions. In addition to methane C-H activation, competition between the initial hydrogen abstraction reaction to form the methane activation product and the tautomerization reaction of this product to form a terminal methylidene was also explored. Several modifications of the PNP and CHtBu ligands were explored to determine the effect of these changes on C-H bond activation. In general, on the one hand, the modifications involving electronic effects have small and inconsistent influence on the stability of the intermediates and products and on the reaction barriers. On the other hand, the use of bulky groups in the ligands favors the methane activation process. By replacing the iPr groups in the PNP ligand with tBu groups, both methane activation and tautomerization reactions become more energetically favorable than in the unmodified complex. On the one hand, the largest acceleration of the methane C-H activation occurs when tBu groups in the phosphine are combined with an extra CH2 linker between the aromatic ring and the phosphine. On the other hand, replacing the nitrogen in the PNP ligand by phosphorus results in lower barriers for the tautomerization reaction and the stabilization of the product of the tautomerization although it remains slightly less stable than product of methane C-H activation. While several ligand modifications related to the electronic effects were examined, it is interesting that most of them did not make a significant change on the barriers for either reaction, indicating a significant resilience of this titanium complex, which could be used to enhance the practical aspects of the complex without a significant loss of its activity.