Improving a Methane C-H Activation Complex by Metal and Ligand Alterations from Computational Results.

We present results for a series of complexes derived from a titanium complex capable of activating C-H bonds under mild conditions (PNP)Ti═CHtBu(CH2tBu), where PNP = N[2-PiPr2-4-methylphenyl]2-. In addition to the initial activation of methane, a tautomerization reaction to a terminal methylidene is also explored due to methylidene's potential use as a synthetic starting point. Analogous complexes with other low-cost 3d transition metals were studied, such as scandium, titanium, vanadium, and chromium as both isoelectronic and isocharged complexes. Our results predict that V(IV) and V(V) complexes are promising for methane C-H bond activation. The V(V) complex has a low rate-determining barrier for methane activation, specifically 16.6 kcal/mol, which is approximately 12 kcal/mol less than that for the Ti complex, as well as having a moderate tautomerization barrier of 29.8 kcal/mol, while the V(IV) complex has a methane activation barrier of 19.0 kcal/mol and a tautomerization barrier of 31.1 kcal/mol. Scandium and chromium complexes are much poorer for C-H bond activation; scandium has very high barriers, while chromium strongly overstabilizes the alkylidene intermediate, potentially stopping the further reaction. In addition to the original PNP ligand, some of the most promising ligands from a previous work were tested, although (as shown previously) modification of the ligand does not typically have large effects on the activity of the system. Our best ligand modification improves the performance of the V(V) complex via the substitution of the nitrogen in PNP by phosphorus, which reduces the tautomerization barrier by 5 to 24.4 kcal/mol.

How flexible is the water molecule structure? Analysis of crystal structures and the potential energy surface.

Water molecules from crystal structures archived in the CSD show a relatively large range both in the bond angle and bond lengths. High level ab initio calculations at the CCSD(T)/CBS level predicted a possibility for energetically low-cost (±1 kcal mol-1) changes of the bond angle and bond lengths in a wide range, from 96.4° to 112.8° and from 0.930 Å to 0.989 Å, respectively.

Unexpected Importance of Aromatic-Aliphatic and Aliphatic Side Chain-Backbone Interactions in the Stability of Amyloids.

The role of aromatic and nonaromatic amino acids in amyloid formation has been elucidated by calculating interaction energies between ß-sheets in amyloid model systems using density functional theory (B3LYP-D3/6-31G*). The model systems were based on experimental crystal structures of two types of amyloids: (1) with aromatic amino acids, and (2) without aromatic amino acids. Data show that these two types of amyloids have similar interaction energies, supporting experimental findings that aromatic amino acids are not essential for amyloid formation. However, different factors contribute to the stability of these two types of amyloids. In the former, the presence of aromatic amino acids significantly contributes to the strength of interactions between side chains; interactions between aromatic and aliphatic side chains are the strongest, followed by aromatic-aromatic interactions, while aliphatic-aliphatic interactions are the weakest. In the latter, that is, the amyloids without aromatic residues, stability is provided by interactions of aliphatic side chains with the backbone and, in some cases, by hydrogen bonds.

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.

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.

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.

What are the preferred horizontal displacements of aromatic-aromatic interactions in proteins? Comparison with the calculated benzene-benzene potential energy surface.

The data from protein structures from the Protein Data Bank and quantum chemical calculations indicate the importance of aromatic-aromatic interactions at large horizontal displacements (offsets). The protein stacking interactions of the phenylalanine residue show preference for large offsets (3.5-5.0 Å), while the calculations show substantially strong interactions, of about -2.0 kcal mol(-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 interactions of Ni(acac) chelates with benzene: calculated interaction energies.

Piling 'em up: The stacking energy of the [Ni(acac)2]/benzene system is calculated at local CCSD(T) level and is in good agreement with the values obtained with the SCS-MP2 method. Energies calculated with several DFT-D methods are somewhat overestimated. The calculated stacking energy of the [Ni(acac)2]/benzene system is significantly stronger than that of the benzene dimer.

The influence of water molecule coordination to a metal ion on water hydrogen bonds.

The geometry of hydrogen bonds in the crystal structures from the Cambridge Structural Database and calculated data show that water coordination to a metal ion has a remarkable influence on hydrogen bonds. The calculated energies of hydrogen bonds of coordinated water are much stronger, even if the aqua complex is neutral.

Water: new aspect of hydrogen bonding in the solid state.

All water-water contacts in the crystal structures from the Cambridge Structural Database with d OO ≤ 4.0 Šhave been found. These contacts were analysed on the basis of their geometries and interaction energies from CCSD(T)/CBS calculations. The results show 6729 attractive water-water contacts, of which 4717 are classical hydrogen bonds (d OH ≤ 3.0 Šand α ≥ 120°) with most being stronger than -3.3 kcal mol-1. Beyond the region of these hydrogen bonds, there is a large number of attractive interactions (2062). The majority are antiparallel dipolar interactions, where the O-H bonds of two water molecules lying in parallel planes are oriented antiparallel to each other. Developing geometric criteria for these antiparallel dipoles (ß1, ß2 ≥ 160°, 80 ≤ α ≤ 140° and T HOHO > 40°) yielded 1282 attractive contacts. The interaction energies of these antiparallel oriented water molecules are up to -4.7 kcal mol-1, while most of the contacts have interaction energies in the range -0.9 to -2.1 kcal mol-1. This study suggests that the geometric criteria for defining attractive water-water interactions should be broader than the classical hydrogen-bonding criteria, a change that may reveal undiscovered and unappreciated interactions controlling molecular structure and chemistry.

What Is Special about Aromatic-Aromatic Interactions? Significant Attraction at Large Horizontal Displacement.

High-level ab initio calculations show that the most stable stacking for benzene-cyclohexane is 17% stronger than that for benzene-benzene. However, as these systems are displaced horizontally the benzene-benzene attraction retains its strength. At a displacement of 5.0 Å, the benzene-benzene attraction is still ∼70% of its maximum strength, while benzene-cyclohexane attraction has fallen to ∼40% of its maximum strength. Alternatively, the radius of attraction (>2.0 kcal/mol) for benzene-benzene is 250% larger than that for benzene-cyclohexane. Thus, at relatively large distances aromatic rings can recognize each other, a phenomenon that helps explain their importance in protein folding and supramolecular structures.

Green Light-Responsive CO-Releasing Polymeric Materials Derived from Ring-Opening Metathesis Polymerization.

Carbon monoxide (CO) is an important biological gasotransmitter in living cells. Precise spatial and temporal control over release of CO is a major requirement for clinical application. To date, the most reported carbon monoxide releasing materials use expensive fabrication methods and require harmful and poorly designed tissue-penetrating UV irradiation to initiate the CO release precisely at infected sites. Herein, we report the first example of utilizing a green light-responsive CO-releasing polymer P synthesized via ring-opening metathesis polymerization. Both monomer M and polymer P were very stable under dark conditions and CO release was effectively triggered using minimal power and low energy wavelength irradiation (550 nm, ≤28 mW). Time-dependent density functional theory (TD-DFT) calculations were carried out to simulate the electronic transition and insight into the nature of the excitations for both L and M. TD-DFT calculations indicate that the absorption peak of M is mainly due to the excitation of the seventh singlet excited state, S7. Furthermore, stretchable materials using polytetrafluoroethylene (PTFE) strips based on P were fabricated to afford P-PTFE, which can be used as a simple, inexpensive, and portable CO storage bandage. Insignificant cytotoxicity as well as cell permeability was found for M and P against human embryonic kidney cells.

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.

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.