New Aspects of Alcohol-Alcohol and Alcohol-Water Interactions: Crystallographic and Quantum Chemical Studies of Antiparallel O-H/O-H Interactions.

New modes of interaction, antiparallel O-H/O-H interactions of alcohol-alcohol dimers and alcohol-water dimers, were studied by analyzing data in the Cambridge Structural Database (CSD) and by calculating potential energy surfaces at a very accurate quantum chemical CCSD(T)/CBS level. The data reveal the existence of antiparallel interactions in crystal structures and significant interaction energies. Data from the CSD for alcohol-alcohol dimers show 49.2% of contacts with classical hydrogen bonds and 10.1% of contacts with antiparallel interactions, while for alcohol-water dimers, 59.4% of contacts are classical hydrogen bonds and only 0.6% of contacts are antiparallel interactions. The calculations were performed on methanol, ethanol, and n-propanol dimers. Classical hydrogen-bonded alcohol-alcohol and alcohol-water dimers have interaction energies of up to -6.2 kcal/mol and up to -5.5 kcal/mol, respectively. Antiparallel interactions in alcohol-alcohol and alcohol-water dimers have interaction energies of up to -4.7 kcal/mol and up to -4.4 kcal/mol, respectively. Symmetry-adapted perturbation theory analysis for antiparallel interactions shows their electrostatic nature.

Computational and crystallographic study of hydrogen bonds in the second coordination sphere of chelated amino acids with a free water molecule: Influence of complex charge and metal ion.

Hydrogen bonds of glycine complexes were calculated using quantum chemistry calculations at M06L-GD3/def2-TZVPP level and by analyzing the crystal structures from the Cambridge Structural Database (CSD). One hydrogen bond where amino acid plays the role of the H-donor (NH/O), and two where it plays the role of the H-acceptor (O1/HO, O1 is a coordinated oxygen atom, and, O2/HO, O2 is a non-coordinated oxygen atom) were investigated. The calculations were done on octahedral nickel(II), square pyramidal copper(II), square planar copper(II), palladium(II), and platinum(II) glycine complexes with different charges adjusted using water(s) and/or chlorine ion(s) as the remaining ligands. For NH/O hydrogen bond, interaction energies of neutral complexes are the weakest, from -5.2 to -7.2 kcal/mol for neutral, stronger for singly positive, from -8.3 to -12.1 kcal/mol, and the strongest for doubly positive complex, -16.9 kcal/mol. For O1/HO and O2/HO interactions, neutral complexes have weaker interaction energies (from -2.2 to -5.1 kcal/mol for O1/HO, and from -3.7 to -5.0 kcal/mol for O2/HO), than for singly negative complexes (from -6.9 to -8.2 kcal/mol for O1/HO, and from -8.0 to -9.0 kcal/mol for O2/HO). Additionally to the complex charge, metal oxidation number, coordination number, and metal atomic number also influence the hydrogen bond strength, however, the influence is smaller.

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.

Hydrogen bonds of a water molecule in the second coordination sphere of amino acid metal complexes: Influence of amino acid coordination.

The hydrogen bonds of free and coordinated amino acids with water molecule were studied by analyzing data in the crystal structures from the Cambridge Structural Database (CSD) and by quantum chemical calculations. The CSD data indicate bifurcated NH/O hydrogen bonds and O1/HO hydrogen bonds of coordinated oxygen. The O/HO hydrogen bonds of free zwitterions and non-coordinated carbonyl oxygen (O2/HO) in metal complexes form primarily linear, non-bifurcated hydrogen bonds. Calculated M06L-GD3/def2-TZVPP interaction energies for free zwitterions (glycine, cysteine, phenylalanine and, serine) and water molecule are in the range from -5.1 to -9.6 kcal/mol for NH/O and from -6.9 to -7.6 kcal/mol for O/HO interactions. Coordinated amino acids in neutral octahedral cobalt(III) complexes have NH/O interaction energies ca. -7.4 kcal/mol, independent of the amino acid. The singly and doubly charged complexes have stronger NH/O interactions; the strongest has energy of -16.9 kcal/mol. In the case of O1/HO hydrogen bond, the interaction energy decreases upon coordination; interactions are quite weak for neutral complexes (-2.2 to -2.6 kcal/mol). For O2/HO hydrogen bonds, all amino acids except serine show slightly stronger interaction in singly negative complexes (-6.3 to -8.0 kcal/mol), while interactions are weaker for neutral complexes (-2.8 to -4.4 kcal/mol), comparing to zwitterions.

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.

New Type of Aromatic π-Systems for Anion Recognition: Strong Anion-π and C-H⋠⋠⋠Anion Interactions Between Halides and Aromatic Ligands in Half-Sandwich Compounds.

Half-sandwich compounds of benzene, cyclopentadienyl, pentamethylcyclopentadienyl, and indenyl were studied as a new type of aromatic π-systems for interactions with halide anions. Although uncoordinated benzene forms only C-H⋅⋅⋅anion interactions, and hexafluorobenzene forms only anion-π interactions, aromatic ligands in half-sandwich compounds can form both types of interactions, because their entire electrostatic potential surface is positive. These aromatic ligands can form stronger anion-π interactions than organic aromatic molecules, as a consequence of more pronounced dispersion and induction energy components. Moreover, C-H⋅⋅⋅anion interactions of aromatic ligands are stronger than anion-π interactions, and significantly stronger than C-H⋅⋅⋅anion interactions of benzene. Our study shows that transition-metal coordination can make aromatic moieties suitable for strong interactions with anions, and gives insight into the design of new anion receptors.

Stacking interactions of the methylated cyclopentadienyl ligands in the crystal structures of transition metal complexes.

In the crystal structures of methylated cyclopentadienyl (Cp) complexes (MeCp, Me4Cp and Me5Cp) deposited in the Cambridge Structural Database, certain orientation types of stacked contacts can be noted as the most frequent. These orientation preferences can be well explained by the matching of oppositely charged regions of electrostatic potential. Parallel displaced stacking, large offset stacking and C-H...π interactions are the dominant interaction types that are responsible for the arrangement in the crystal structures of stacked methylated Cp complexes.

The Affinity of Some Lewis Bases for Hexafluoroisopropanol as a Reference Lewis Acid: An ITC/DFT Study.

To figure out the possible role of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as well as to provide reference thermochemical data in solution, the formation of Lewis acid-base complexes between HFIP (Lewis acid) and a series of 8 different Lewis bases (3 sulfoxides, 3 Nsp2 pyridine derivatives, 1 aromatic amine, 1 cyclic aliphatic ether) was examined by isothermal titration calorimetry (ITC) experiments and static density functional theory augmented with Dispersion (DFT-D) calculations. Measured ITC association enthalpy values (ΔHa ) lie between -9.3 and -14 kcal mol-1 . Computations including a PCM implicit solvation model produced similar exothermicity of association of all studied systems compared to the ITC data with ΔHa values ranging from -8.5 to -12.7 kcal mol-1 . An additional set of calculations combining implicit and explicit solvation by chlorobenzene of the reactants, pointed out the relatively low interference of the solvent with the HFIP-base complexation: its main effect is to slightly enhance the Gibbs energy of the HFIP-Lewis base association. It is speculated that the interactions of bulk HFIP with Lewis bases therefore may significantly intervene in catalytic processes not only via the dynamic microstructuring of the medium but also more explicitly by affecting bonds' polarization at the Lewis bases.

Stacking interactions of resonance-assisted hydrogen-bridged rings and C6-aromatic rings.

Stacking interactions between six-membered resonance-assisted hydrogen-bridged (RAHB) rings and C6-aromatic rings were systematically studied by analyzing crystal structures in the Cambridge Structural Database (CSD). The interaction energies were calculated by quantum-chemical methods. Although the interactions are stronger than benzene/benzene stacking interactions (-2.7 kcal mol-1), the strongest calculated RAHB/benzene stacking interaction (-3.7 kcal mol-1) is significantly weaker than the strongest calculated RAHB/RAHB stacking interaction (-4.7 kcal mol-1), but for a particular composition of RAHB rings, RAHB/benzene stacking interactions can be weaker or stronger than the corresponding RAHB/RAHB stacking interactions. They are also weaker than the strongest calculated stacking interaction between five-membered saturated hydrogen-bridged rings and benzene (-4.4 kcal mol-1) and between two five-membered saturated hydrogen-bridged rings (-4.9 kcal mol-1). SAPT energy decomposition analyses show that the strongest attractive term in RAHB/benzene stacking interactions is dispersion, however, it is mostly canceled by a repulsive exchange term; hence the geometries of the most stable structures are determined by an electrostatic term.

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.

Carbohydrate - Protein aromatic ring interactions beyond CH/π interactions: A Protein Data Bank survey and quantum chemical calculations.

The geometries of the contacts between monosaccharides and aromatic rings of amino acids found in X-ray crystallography structures, in the Protein Data Bank (PDB), were analyzed, while the energies of the interactions were calculated using quantum chemical method. We found 1913 sugar/aromatic ring contacts, 1054 of them (55%) with CH/π interactions and 859 of them (45%) without CH/π interactions. We showed that only the carbohydrate/aromatic contacts with CH/π interactions are preferentially parallel and enable sliding in the plane parallel to aromatic ring. The calculated interaction energies in systems with CH/π interactions are in the range from -1.7 kcal/mol to -6.8 kcal/mol, while in the systems without CH/π interactions are in the range -0.2 to -3.2 kcal/mol. Hence, the binding that does not include CH/π interactions, can also be important for aromatic amino acid and carbohydrate binding processes, since some of these interactions can be as strong as the CH/π interactions. At the same time, these interactions can be weak enough to enable releasing of small carbohydrate fragments after the enzymatic reaction. The analysis of the protein-substrate patterns showed that every second or third carbohydrate unit in long substrates stacks with protein aromatic amino acids.

Role of aromatic amino acids in amyloid self-assembly.

Amyloids are proteins of a cross-ß structure found as deposits in several diseases and also in normal tissues (nails, spider net, silk). Aromatic amino acids are frequently found in amyloid deposits. Although they are not indispensable, aromatic amino acids, phenylalanine, tyrosine and tryptophan, enhance significantly the kinetics of formation and thermodynamic stability, while tape or ribbon-like morphology is represented in systems with experimentally detected π-π interactions between aromatic rings. Analysis of geometries and energies of the amyloid PDB structures indicate the prevalence of aromatic-nonaromatic interactions and confirm that aromatic-aromatic interactions are not crucial for the amyloid formation.

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.

The Structural Details of Aspirin Molecules and Crystals.

We revisit, in the key of structural chemistry, one of the most known and important drugs: the aspirin. Although apparently simple, the factors determining the molecular structure and supramolecular association in crystals are not trivial. We addressed the problem from experimental and theoretical sides, considering issues from X-ray measurements and results of first-principle reconstruction of molecule and lattices by ab initio calculations. Some puzzling problems can give headaches to specialists and intrigue the general public. Thus, the reported polymorphism of aspirin is disputed, a so-called form II being alleged as a result of misinterpretation. At the same time, were presented evidences that the structure of common form I can be disrupted by domains where the regular packing is changed to the pattern of form II. The problems appear even at the level of independent molecule: the most stable conformation computed by various techniques of electronic structure differs from those encountered in crystals. Because the energy difference between the related conformational isomers (computed as most stable vs. the experimental structure) is small, about 1 kcal/mol, comprised in the error bars of used methods, the unresting question is whether the modelling is imprecise, or the supramolecular factors are mutating the conformational preferences. By a detective following of the issue, the intermolecular effects were made responsible for the conformation of the molecule in crystal. The presented problems were gathered from literature results, debates, glued with modelling and analysis redone by ourselves, in order to secure the unitary view of the considered prototypic topic.

Stacking interactions of borazine: important stacking at large horizontal displacements and dihydrogen bonding governed by electrostatic potentials of borazine.

Potential energy surfaces of borazine-benzene and borazine-borazine stacking interactions were studied by performing DFT, CCSD(T)/CBS and SAPT calculations. The strongest borazine-benzene stacking was found in a parallel-displaced geometry, with a CCSD(T)/CBS interaction energy of -3.46 kcal mol-1. The strongest borazine-borazine stacking has a sandwich geometry, with a CCSD(T)/CBS interaction energy of -3.57 kcal mol-1. The study showed that borazine forms significant stacking interactions at large horizontal displacements (over 4.5 Å), with energies of -2.20 kcal mol-1 for the borazine-benzene and -1.96 kcal mol-1 for the borazine-borazine system. The strength of interactions and their geometrical preferences can be rationalized by observing the electrostatic potentials of borazine and benzene, which is in agreement with SAPT analysis showing that electrostatics is the most important energy component for borazine stacking. All the interactions found in crystal structures of borazine and related compounds were identified either as potential curve minima or the geometries obtained from their optimizations. We also report a new dihydrogen bonding dimer with a CCSD(T)/CBS interaction energy of -2.37 kcal mol-1, which is encountered in the borazine crystal structures and enables the formation of additional simultaneous interactions that contribute to the overall stability of the crystals.

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.

Strong stacking interactions of metal-chelate rings are caused by substantial electrostatic component.

Symmetry Adapted Perturbation Theory (SAPT) analysis shows that stacking interactions of metal-chelate rings are stronger than stacking interactions of organic molecules due to much stronger electrostatic interactions caused by the presence of metals. Depending on the ligand, electrostatic component of chelate stacking can be stronger than dispersion component.

Binding of metal ions and water molecules to nucleic acid bases: the influence of water molecule coordination to a metal ion on water-nucleic acid base hydrogen bonds.

The interactions of nucleic acid bases with non-coordinated and coordinated water molecules were studied by analyzing data in the Protein Data Bank (PDB) and by quantum chemical calculations. The analysis of the data in the crystal structures from the PDB indicates that hydrogen bonds involving oxygen or nitrogen atoms of nucleic acid bases and water molecules are shorter when water is bonded to a metal ion. These results are in agreement with the quantum chemical calculations on geometries and interaction energies of hydrogen bonds; the calculations on model systems show that hydrogen bonds of nucleic acid bases with water bonded to a metal ion are stronger than hydrogen bonds with non-coordinated water. These calculated values are similar to the strength of hydrogen bonds between nucleic acid bases. The results presented in this paper may be relevant to understand the role of water molecules and metal ions in the process of replication and stabilization of nucleic acids and also to understand the possible toxicity of metal ion interactions with nucleic acids.

Study of stacking interactions between two neutral tetrathiafulvalene molecules in Cambridge Structural Database crystal structures and by quantum chemical calculations.

Tetrathiafulvalene (TTF) and its derivatives are very well known as electron donors with widespread use in the field of organic conductors and superconductors. Stacking interactions between two neutral TTF fragments were studied by analysing data from Cambridge Structural Database crystal structures and by quantum chemical calculations. Analysis of the contacts found in crystal structures shows high occurrence of parallel displaced orientations of TTF molecules. In the majority of the contacts, two TTF molecules are displaced along their longer C2 axis. The most frequent geometry has the strongest TTF-TTF stacking interaction, with CCSD(T)/CBS energy of -9.96 kcal mol-1. All the other frequent geometries in crystal structures are similar to geometries of the minima on the calculated potential energy surface.

Influence of chelate ring type on chelate-chelate and chelate-aryl stacking: the case of nickel bis(dithiolene).

Chelate-aryl and chelate-chelate stacking interactions of nickel bis(dithiolene) were studied at the CCSD(T)/CBS and DFT levels. The strongest chelate-aryl stacking interaction between nickel bis(dithiolene) and benzene has a CCSD(T)/CBS stacking energy of -5.60 kcal mol-1. The strongest chelate-chelate stacking interactions between two nickel bis(dithiolenes) has a CCSD(T)/CBS stacking energy of -10.34 kcal mol-1. The most stable chelate-aryl stacking has the benzene center above the nickel atom, while the most stable chelate-chelate dithiolene stacking has the chelate center above the nickel atom. Comparison of chelate-aryl stacking interactions of dithiolene and acac-type nickel chelate shows similar strength. However, chelate-chelate stacking is stronger for dithiolene nickel chelate than for acac-type nickel chelate, which has a CCSD(T)/CBS interaction energy of -9.50 kcal mol-1.