Orwik

A donor-functionalized, silyl-substituted pentadienyllithium: structural insight from experiment and theory.

A donor-functionalized, silyl-substituted pentadienyllithium has been synthesized and characterized by crystallography and NMR spectroscopy. The pentadienyl negative charge was found to be partially localized, which DFT revealed to be due to the pola... expand abstractrizing power of the lithium cation. collapse abstract

A multi-scale approach to spin crossover in Fe(ii) compounds.

We report here for the first time a multi-scale study on the concept of spin-crossover compounds, which integrates improved density functionals, a polarizable force field and hybrid QM/MM calculations. This multi-scale setup is applied to the tempera... expand abstractture dependence of spin states of a Fe(ii) compound with trispyrazolylborate ligands that exhibits spin-crossover. Our study shows a transition temperature of around 290 K, which is in perfect agreement with experimental results. Moreover, based on our data we provide the origin of why spin transition occurs in this iron-compound: it results directly from spin-state changes in the iron-compound that lead to more favourable electrostatic interactions for the high-spin state. collapse abstract

Nuclear shieldings with the SSB-D functional.

The recently reported SSB-D functional [J. Chem. Phys. 2009, 131, 094103] is used to check the performance for obtaining nuclear magnetic resonance (NMR) shielding constants. Four different databases were studied, which contain a diversity of molecul... expand abstractes and nuclear shielding constants. The SSB-D functional is compared with its "parent" functionals (PBE, OPBE), the KT2 functional that was designed specially for NMR applications and the coupled cluster CCSD(T) method. The best performance for the experimentally most-used elements ((1)H, (13)C) is obtained for the SSB-D and KT2 functionals. collapse abstract

The reactivity of endohedral fullerenes. What can be learnt from computational studies?

The last two decades have witnessed major advances in the synthesis and characterization of endohedral fullerenes. These species have interesting physicochemical properties with many potential interesting applications in the fields of magnetism, supe... expand abstractrconductivity, nonlinear optical properties, radioimmunotherapy, and magnetic resonance imaging contrast agents, among others. In addition to the synthesis and characterization, the chemical functionalization of these species has been a main focus of research for at least four reasons: first, to help characterize endohedral fullerenes that could not be well described structurally otherwise; second, to generate materials with fine-tuned properties leading to enhanced functionality in one of their multiple potential applications; third, to produce water-soluble endohedral fullerenes needed for their use in medicinal sciences; and fourth, to generate electron donor-acceptor conjugates that can be used in solar energy conversion/storage. The functionalization of these species has been achieved through different types of reactions, the most common being the Diels-Alder reactions, 1,3-dipolar cycloadditions, Bingel-Hirsch reactions, and free-radical reactions. It has been found that the performance of these reactions in endohedral fullerenes may be quite different from that of the empty fullerenes. Indeed, encapsulated species have a large influence on the thermodynamics, kinetics, and regiochemistry of these reactions. A detailed understanding of the changes in chemical reactivity due to incarceration of atoms or clusters of atoms is essential to assist the synthesis of new functionalized endohedral fullerenes with specific properties. This Perspective seeks to highlight the key role played by computational chemistry in the analysis of the chemical reactivity of these systems. It is shown that the information obtained through calculations is highly valuable in the process of designing new materials based on endohedral fullerenes. collapse abstract

Inter- and intramolecular dispersion interactions.

We have investigated the performance of a variety of density functional methods for weak intra- and intermolecular dispersion interactions. Grimme's empirical dispersion correction method is shown to give a good description for these interactions and... expand abstract helps to improve the description of water-hexamer isomers, noble-gas dimers, hydrocarbon C(12)H(12) isomers, branching energy of linear versus branched octane, dissociation of the covalently bound anthracene dimer, and stacking within the adenine dimer. However, the dispersion correction does not correct all shortcomings of the different density functionals, which leads to sizeable differences compared to ab initio CCSD(T) and experimental reference data. The only exception is shown to be our recently presented SSB-D functional that works well for all systems studied here. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010. collapse abstract

Molecular mechanism of acid-triggered aryl-halide reductive elimination in well-defined aryl-Cu(III)-halide species.

Well-defined aryl-Cu(III)-halide species undergo reductive elimination upon acid addition resulting in the formation of strong aryl-halide bonds. The computationally studied mechanism points towards ligand protonation as the rate-determining step, in... expand abstract agreement with previous experimental data. collapse abstract

Performance of 3D-space-based atoms-in-molecules methods for electronic delocalization aromaticity indices.

Several definitions of an atom in a molecule (AIM) in three-dimensional (3D) space, including both fuzzy and disjoint domains, are used to calculate electron sharing indices (ESI) and related electronic aromaticity measures, namely, I(ring) and multi... expand abstractcenter indices (MCI), for a wide set of cyclic planar aromatic and nonaromatic molecules of different ring size. The results obtained using the recent iterative Hirshfeld scheme are compared with those derived from the classical Hirshfeld method and from Bader's quantum theory of atoms in molecules. For bonded atoms, all methods yield ESI values in very good agreement, especially for C-C interactions. In the case of nonbonded interactions, there are relevant deviations, particularly between fuzzy and QTAIM schemes. These discrepancies directly translate into significant differences in the values and the trends of the aromaticity indices. In particular, the chemically expected trends are more consistently found when using disjoint domains. Careful examination of the underlying effects reveals the different reasons why the aromaticity indices investigated give the expected results for binary divisions of 3D space. (c) 2010 Wiley Periodicals, Inc. J Comput Chem, 2010. collapse abstract

Spin-state-corrected Gaussian-type orbital basis sets.

Recently, we reported that the basis set has a profound influence on the computed values for spin-state splittings [J. Phys. Chem. A 2008, 112, 6384]. In particular, small Gaussian-type orbital (GTO) basis sets were shown to be unreliable for the pre... expand abstractdiction of them. Here, we report simple modifications of the small Pople-type Gaussian-type orbital basis sets (3-21G, 3-21G*, 6-31G, 6-31G*), which correct their faulty behavior for the spin-state energies. We have investigated the basis sets for a set of 13 first-row transition-metal complexes for which reliable reference data have been obtained at the OPBE/TZ2P(STO) level. For several systems, we have used single and double spin-contamination corrections to avoid ambiguity of the results because of spin contamination, that is, the energies and geometries were obtained for the pure spin states. The spin ground states as predicted by the spin-state-corrected GTO basis sets (s6-31G, s6-31G*) are in complete agreement with the reference Slater-type orbital (STO) data, while those of the original basis sets and a recent modification by Baker and Pulay (m6-31G*) are not for all cases. The spin-state-corrected GTO basis sets also improve upon the original and modified basis sets for the accuracy of geometry optimization, while the accuracy of the vibrational frequencies is as good or better. At a limited additional cost, one therefore obtains very reliable results for these important spin-state energies. collapse abstract

Patterns of pi-electron delocalization in aromatic and antiaromatic organic compounds in the light of Hückel's 4n + 2 rule.

The total pi-electron delocalization of a series of classical aromatic and antiaromatic organic compounds is separated into ortho (1,2), meta (1,3), para (1,4), and successive contributions (the so-called delocalization crossed terms) and the changes... expand abstract that take place in these crossed terms when two electrons are added or removed are analyzed. Our results show that these changes follow a similar alternation pattern in all cases. The patterns found represent a kind of electronic footprints that makes it possible to discern between aromatic and antiaromatic systems. collapse abstract

Reactivity and regioselectivity of noble gas endohedral fullerenes ngc(60) and ng(2)c(60) (nghe-xe).

Ene reactions between two alkynes? Doors open to thermally induced cycloisomerization of macrocyclic triynes and enediynes.

A domino process is described combining an ene reaction between two alkynes and a Diels-Alder cycloaddition of the vinylallene formed. The process accounts for the thermally induced cycloisomerization of macrocyclic triynes and enediynes to give fuse... expand abstractd tetracycles in a stereoselective manner. collapse abstract

On the mechanism of action of fullerene derivatives in superoxide dismutation.

We have studied the mechanism of the antioxidant activity of C(60) derivatives at the BP86/TZP level with inclusion of solvent effects (DMSO) by using the COSMO approach. The reaction studied here involves degradation of the biologically relevant sup... expand abstracteroxide radical (O(2)(*-)), which is linked to tissue damage in several human disorders. Several fullerene derivatives have experimentally been shown to be protective in cell culture and animal models of injury, but precisely how these compounds protect biological systems is still unknown. We have investigated the activity of tris-malonyl C(60) (also called C(3)), which efficiently removes the superoxide anion with an activity in the range of several biologically effective, metal-containing superoxide dismutase mimetics. The antioxidant properties of C(3) are attributed to the high affinity of C(60) to accept electrons. Our results show that once the superoxide radical is in contact with the surface of C(3), its unpaired electron is transferred to the fullerene. This process, which converts the damaging O(2)(*-) to neutral oxygen O(2), is the rate-determining step of the reaction. Afterwards, another superoxide radical reacts with C(3)(*-) to form hydrogen peroxide and in the process takes up the additional electron that was transferred in the first step. The overall process is clearly exothermic and, in general, involves reaction steps with relatively low activation barriers. The capability of C(3) to degrade a highly reactive oxygen species that is linked to several human diseases is of immediate interest for future applications in the field of biology and medicine. collapse abstract

Computational methods to predict the reactivity of nanoparticles through structure-property relationships.

Importance of the field: Innovative biomedical techniques operational at the nanoscale level are being developed in therapeutics, including advanced drug delivery systems and targeted nanotherapy. Given the large number of nanoparticles that are bein... expand abstractg developed for possible biomedical use, the use of computational methods in the assessment of their properties is of key importance. Areas covered in this review: Among the in silico methods, quantum mechanics is still used rarely in the study of nanostructured particles. This review provides an overview of some of the main quantum mechanics methods that are already used in the assessment of chemicals. Furthermore, classical tools used in the chemistry field are described, to show their potential also in the pharmacological field. What the reader will gain: The current status of computational methods in terms of availability and applicability to nanoparticles, and recommendations for further research are highlighted. Take home message: The in silico modelling of nanoparticles can assist in targeting and filling gaps in knowledge on the effects of these particular particles. Computational models of the behaviour of nanoparticles in biological systems, including simulation models for predicting intermolecular interactions and harmful side effects, can be highly valuable in screening candidate particles for potential biomedical use in diagnostics, imaging and drug delivery. collapse abstract

Examining the planarity of poly(3,4-ethylenedioxythiophene): consideration of self-rigidification, electronic, and geometric effects.

The intramolecular interactions responsible for the planarity observed in poly(3,4-ethylenedioxythiophene) and small 3,4-ethylenedioxythiophene-containing oligomers have been investigated using quantum mechanical methods. Specifically, the relative i... expand abstractnfluence of electron-donating effects, pi-conjugation, and geometric restrictions induced by the cyclic substituent and attractive S...O intramolecular noncovalent interactions, which were proposed to be the most relevant factor for such planarity on the self-rigidification observed in these compounds, have been examined considering a wide number of model compounds. Results evidenced that noncovalent S...O interactions, which were postulated on the basis that the nonbonded distances between sulfur and oxygen atoms belonging to neighboring repeating units are significantly shorter than the sum of the van der Waals radii of sulfur and oxygen, are slightly repulsive destabilizing the planar anti conformation. In contrast, the latter arrangement is favored by the pi-conjugation produced by both geometric restrictions imposed by the cyclic substituent and the electron-donating effects provided by the oxygen atoms attached to positions three and four of each tiophene ring. Therefore, these factors produce gain in aromaticity and favorable electrostatic interactions when the planarity is reached, compensating the Pauli repulsions between the shared electron pairs of the sulfur and oxygen atoms. collapse abstract

Spin-state splittings of iron(II) complexes with trispyrazolyl ligands

We report a computational study at the OPBE/TZP level on the chemical bonding and spin ground-states of mono-nuclear iron(II) complexes with trispyrazolylborate and trispyrazolylmethane ligands. We are in particular interested in how substitution pat... expand abstractterns on the pyrazolyl-rings influence the spin-state splittings, and how they can be rationalized in terms of electronic and steric effects. One of the main observations of this study is the large similarity of the covalent metal–ligand interactions for both the borate and methane ligands. Furthermore, we find that the spin-state preference of an individual transition-metal (TM) complex does not always concur with that of an ensemble of TM-complexes in the solid-state. Finally, although the presence of methyl groups at the 3-position of the pyrazolyl groups leads to ligand–ligand repulsion, it is actually the loss of metal–ligand bonding interactions that is mainly responsible for shifts in spin-state preferences. collapse abstract

Structural studies on the full-length LysR-type regulator TsaR from Comamonas testosteroni T-2 reveal a novel open conformation of the tetrameric LTTR fold.

LysR-type transcriptional regulators (LTTRs) constitute the largest family of regulators in prokaryotes. The full-length structures of the LTTR TsaR from Comamonas testosteroni T-2 and its complex with the natural inducer para-toluensulfonate have be... expand abstracten characterized by X-ray diffraction. Both ligand-free and complexed forms reveal a dramatically different quaternary structure from that of CbnR from Ralstonia eutropha, or a putative LysR-type regulator from Pseudomonas aeruginosa, the only other determined full-length structures of tetrameric LTTRs. Although all three show a head-to-head tetrameric ring, TsaR displays an open conformation, whereas CbnR and PA01-PR present additional contacts in opposing C-terminal domains that close the ring. Such large differences may be due to a broader structural versatility than previously assumed or either, reflect the intrinsic flexibility of tetrameric LTTRs. On the grounds of the sliding dimer hypothesis of LTTR activation, we propose a structural model in which the closed structures could reflect the conformation of a ligand-free LTTR, whereas inducer binding would bring about local changes to disrupt the interface linking the two compact C-terminal domains. This could lead to a TsaR-like, open structure, where the pairs of recognition helices are closer to each other by more than 10 A. collapse abstract

Reactivity and Regioselectivity of Noble Gas Endohedral Fullerenes NgC60 and Ng2C60 (NgHe–Xe)

Recently, it was shown that genuine NgNg chemical bonds are present in the endohedral fullerenes Ng2@C60 in the case of Ng=Xe, while it is more debatable whether a chemical bond exist for Ng=Ar and Kr. The lighter homologues with helium and neon are ... expand abstractweakly bonded van der Waals complexes. The presence of a noble gas dimer inside the cage is expected to modify the exohedral reactivity of the C60 cage with respect to that of free C60. To investigate the impact of encapsulated diatomic noble gas molecules on the chemical reactivity of C60, we analyzed the thermodynamics and the kinetics of [4+2] Diels–Alder cycloaddition of 1,3-cis-butadiene at all nonequivalent bonds in free C60, Ng@C60, and Ng2@C60 (Ng=He, Ne, Ar, Kr, and Xe). Our BP86/TZP calculations reveal that introduction of single noble gas atoms in Ng@C60 and noble gas dimers He2 and Ne2 in Ng2@C60 has almost no effect on the exohedral reactivity compared to free C60, in agreement with experimental results. In all these cases cycloaddition is clearly favored at the [6,6] bonds in the fullerene cage. For the endohedral compounds He2@C60 and Ne2@C60 a slight preference (by less than 2 kcal mol−1) for bonds closer to the C5 symmetry axis is found. This picture changes dramatically for the endohedral compounds with heavier noble gas dimers. Encapsulation of these noble gas dimers clearly enhances the reaction, both under thermodynamic and kinetic control. Moreover, in the case of Xe2@C60, addition to [6,6] and [5,6] bonds becomes equally viable. These reactivity changes in endohedral fullerenes are attributed to stabilization of the LUMO, increased fullerene strain energy, and greater compression of the encapsulated Ng2 unit along the He to Xe series. collapse abstract

Homolytic versus heterolytic dissociation of alkalimetal halides: the effect of microsolvation.

Herein we report density functional calculations of homolytic and heterolytic dissociation energies of the diatomic alkalimetal halides MX (M=Li, Na, K, Rb, and Cs and X=F, Cl, Br, I, and At) and their corresponding microsolvated structures MX(H(2)O)... expand abstract(n) (n=1 to 4). Our results show that the homolytic dissociation energy of the MX(H(2)O)(n) species increases with the number of water molecules involved in the microsolvated salts. On the other hand, the heterolytic dissociation energy follows exactly the opposite trend. As a result, while for the isolated diatomic alkalimetal halides, homolytic dissociation is always favored over heterolytic dissociation, the latter is preferred for CsF and CsCl already for n=2, and for n=4 it is the preferential mode of dissociation for more than half of the species studied. collapse abstract

On the Regioselective Intramolecular Nucleophilic Addition of Thiols to C60

The first intramolecular nucleophilic addition of a thiol to a fullerene double bond is reported. Whereas the reaction of cysteine (4) or cystine (11) with formaldehyde and [60]fullerene in chlorobenzene at reflux afforded the new compound 10 bearing... expand abstract a thiazolidine moiety fused to the fullerene sphere, the reaction of commercially available N-methylglycine (12; sarcosine) with 1,4-dithiane-2,5-diol (13) and C60 in chlorobenzene at reflux led to the desired cyclized compound 3 in poor yield. The favorable geometrical approach of the reactive thiol group towards the fullerene double bond is followed by a 5-exo-trig intramolecular nucleophilic addition of the S–H group to the adjacent double bond of the fullerene to form compound 3 in which a tetrahydrothiophene ring is simultaneously fused to the pyrrolidine and the fullerene moieties. Compound 3 was spectroscopically and electrochemically characterized and CV revealed that saturation of a second double bond of the fullerene sphere (cis-1 regioisomer) is compensated by the electronegative character of the sulfur atom, resulting in reduction potentials similar to those observed for fullerene monoadducts. The two-fold cyclization reaction occurs in a totally regioselective stepwise process leading exclusively to the cis-1 isomer. Theoretical calculations (DFT and the ONIOM approach) predict that the formation of the sulfur pentagonal ring is highly favored and does not present structural constraints. Furthermore, the activation barrier for the nucleophilic attack of the thiol group on the fullerene surface was found to be substantially higher in comparison with the analogous previously reportedhydroxy group (activation barrier about 8 kcal mol–1 larger for SH than for OH), thus accounting for the poor yields of tetrahydrothiophene 3. The formation of 3 competes with the formation of 1,2-dimethylpyrrolidino[3,4:1,2][60]fullerene (15), which is formed as the main reaction product by loss of the SH group. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) collapse abstract

Tuning aromaticity in trigonal alkaline earth metal clusters and their alkali metal salts.

In this work, we analyze the geometry and electronic structure of the [X(n)M(3)](n-2) species (M = Be, Mg, and Ca; X = Li, Na, and K; n = 0, 1, and 2), with special emphasis on the electron delocalization properties and aromaticity of the cyclo-[M(3)... expand abstract](2-) unit. The cyclo-[M(3)](2-) ring is held together through a three-center two-electron bond of sigma-character. Interestingly, the interaction of these small clusters with alkali metals stabilizes the cyclo-[M(3)](2-) ring and leads to a change from sigma-aromaticity in the bound state of the cyclo-[M(3)](2-) to pi-aromaticity in the XM(3) (-) and X(2)M(3) metallic clusters. Our results also show that the aromaticity of the cyclo-[M(3)](2-) unit in the X(2)M(3) metallic clusters depends on the nature of X and M. Moreover, we explored the possibility for tuning the aromaticity by simply moving X perpendicularly to the center of the M(3) ring. The Na(2)Mg(3), Li(2)Mg(3), and X(2)Ca(3) clusters undergo drastic aromaticity alterations when changing the distance from X to the center of the M(3) ring, whereas X(2)Be(3) and K(2)Mg(3) keep its aromaticity relatively constant along this process. collapse abstract

Dötz benzannulation reactions: heteroatom and substituent effects in chromium Fischer carbene complexes.

We have carried out a theoretical investigation of the Dötz reaction between acetylene and a series of chromium Fischer-type carbenes [(CO)(5)Cr=C(X)R] with different representative substituents (R=CH=CH(2), Ph) and heteroatom ligands (X=OH, NH(2), O... expand abstractCH(3), N(CH(3))(2)) by using density functional theory with the B3LYP functional. We have studied the Dötz and chromahexatriene mechanisms of benzannulation and also the reaction mechanism leading to cyclopentannulation. For the benzannulation, it was found that the most likely mechanism in the case of vinylcarbenes is the chromahexatriene route, whereas for phenylcarbenes, the Dötz route via a ketene intermediate is clearly the most favorable. The reactions leading to the cyclopentannulated and benzannulated products are more exothermic with vinylcarbenes than with phenylcarbenes and also more exothermic with alkoxycarbenes than with aminocarbenes. The relative stability of the cyclopentannulated products as compared with the benzannulated products increases for bulkier X substituents and on going from alkoxy- to aminocarbenes. The kinetic data concurs with the experimental product distribution found for vinylcarbenes, by which mainly benzannulated products are obtained, and dimethylaminophenylcarbenes, which lead exclusively to cyclopentannulated adducts. collapse abstract

Competitive retro-cycloaddition reaction in fullerene dimers connected through pyrrolidinopyrazolino rings.

Competitive retro-cycloaddition in [60]- and [70]fullerene homodimers (1a,1c) as well as [60]/[70]heterodimer (1b), linked through 2-pyrazolinopyrrolidino bridges, has been studied by means of HPLC, mass spectrometry, and theoretical calculations at ... expand abstractthe density functional theory (DFT) level by using the two-layered ONIOM approach. The results of these investigations indicate that the retro-cycloaddition reaction of pyrrolidinofullerenes is favored compared to the retro-cycloaddition reaction of 2-pyrazolinofullerenes in compounds 1a-c. Evidence of the occurrence of this process have been observed both by HPLC and MS-MALDI, these findings being in good agreement with those predicted by theoretical calculations. collapse abstract

Radioguided localization of nonpalpable breast cancer lesions: randomized comparison with wire localization in patients undergoing conservative surgery and sentinel node biopsy.

OBJECTIVE: The aim of this investigation was to determine whether radioguided occult lesion localization and routine wire localization differ in respect to the effectiveness of complete excision of nonpalpable breast cancer lesions. SUBJECTS AND METH... expand abstractODS: This prospective randomized study included patients with breast cancer scheduled for conservative tumor excision and sentinel node biopsy. Patients were randomized to either radioguided localization or wire localization. Comparative radiologic, surgical, and pathologic data were collected and analyzed to establish the duration, ease of use, and accuracy of the two techniques for occult lesion localization. The effectiveness of sentinel node biopsy also was assessed. One radiologist and two surgeons participated in the study. RESULTS: Among 134 patients, 68 were treated with wire localization and 66 with radioguided localization. The mean duration of radiologic localization was significantly shorter for radioguided localization (p < 0.001). No statistical differences were found for the other parameters studied. Radiography of the surgical specimen showed 100% lesion excision with both techniques. Complete tumor excision with tumor-free margins was achieved in 89.4% of patients who underwent radioguided localization group and 82.4% of patients who underwent wire localization. Pathologic examination showed the excised tissue volume was slightly larger (p = 0.371) and lesion concentricity slightly less (p = 0.730) with radioguided localization. The sentinel node detection rate was 91% with radioguided localization and 84% with wire localization. CONCLUSION: The radioguided technique is as effective as the standard wire technique for localization and excision of nonpalpable breast cancer lesions and is somewhat faster and simpler to perform than wire localization. collapse abstract

Local aromaticity of pristine and fluorinated carbon nanotubes.

We examine the use of nucleus independent chemical shifts (NICS) as a tool for analysis of pristine and fluorinated finite-length carbon nanotubes. The introduction of both variable molecule length and different nanotube curvatures introduces additio... expand abstractnal subtleties to NICS analysis not present in analysis of more conventional 2D molecules. Notably the precise length of tube segment considered can strongly influence calculated NICS values. We provide specific examples using (6, 6) and (7,7) nanotube segments under fluorination. Although care should be taken when comparing systems of different length or curvature, important chemical information can still be retrieved from the local aromaticity patterns. In particular, local aromaticity is observed to play a relevant role in the orientation towards the ideal C4F addition pattern for fluorinated carbon nanotubes. collapse abstract

A new all-round density functional based on spin states and S(N)2 barriers.

We report here a new empirical density functional that is constructed based on the performance of OPBE and PBE for spin states and S(N)2 reaction barriers and how these are affected by different regions of the reduced gradient expansion. In a previou... expand abstracts study [Swart, Sola, and Bickelhaupt, J. Comput. Methods Sci. Eng. 9, 69 (2009)] we already reported how, by switching between OPBE and PBE, one could obtain both the good performance of OPBE for spin states and reaction barriers and that of PBE for weak interactions within one and the same (SSB-sw) functional. Here we fine tuned this functional and include a portion of the KT functional and Grimme's dispersion correction to account for pi-pi stacking. Our new SSB-D functional is found to be a clear improvement and functions very well for biological applications (hydrogen bonding, pi-pi stacking, spin-state splittings, accuracy of geometries, reaction barriers). collapse abstract