Carbon Atom as an Extremely Strong Nucleophilic and Electrophilic Center: Dendritic Allenes Are Powerful Organic Proton and Hydride Sponges.

Gas-phase proton affinities (PAs) and hydride affinities (HAs) of organic bases possessing an allene moiety and substituted with methyl, dimethylamino, cyano, and vinyl substituents were examined with the B3LYP/6-311+G(2df,p)//B3LYP/6-31G(d) model. It was shown that a number of superbases and hyperbases can be obtained, as well as the potent hydride sponges. Methyl or dimethylamino substituents increased the proton affinity of the parent molecule, and the cyano substituents increased its hydride affinity. When the vinyl substituents are placed on allene, both the hydride and the proton affinities increased. A disubstituted allene with two dimethylamino groups is the smallest studied superbase, whereas the allene tetrasubstituted with four vinyl groups gives the smallest superbase possessing only alkene substituents. By introducing the vinyl group as a repeating subunit, one can obtain dendritic structures with the investigated substituents determining its properties. By changing the dimethylamino with the cyano group, a dendrimeric molecule can change from a hyperbase with a proton affinity of 324.6 kcal mol-1 to a very strong hydride ion acceptor with a hydride affinity of 205.4 kcal mol-1, while possessing the same proton or hydride ion attachment site.

Hydrogen bond dynamics of histamine monocation in aqueous solution: Car-Parrinello molecular dynamics and vibrational spectroscopy study.

Hydration of histamine was examined by infrared spectroscopy and Car-Parrinello molecular dynamics simulation. Histamine is a neurotransmitter and inflammation mediator, which at physiological pH conditions is present mainly in monocationic form. Our focus was on the part of vibrational spectra that corresponds to histamine N-H stretching, since these degrees of freedom are essential for its interactions with either water molecules or transporters and receptors. Assignment of the experimental spectra revealed a broad feature between 3350 and 2300 cm(-1), being centered at 2950 cm(-1), which includes a mixed contribution from the ring N-H and the aminoethyl N-H stretching vibrations. Computational analysis was performed in two ways: first, by making Fourier transformation on the autocorrelation function of all four N-H bond distances recorded during CPMD run, and second, and most importantly, by incorporating quantum effects through applying an a posteriori quantization of all N-H stretching motions utilizing our snapshot analysis of the fluctuating proton potential. The one-dimensional vibrational Schrödinger equation was solved numerically for each snapshot, and the N-H stretching envelopes were calculated as a superposition of the 0→1 transitions. The agreement with the experiment was much better in the case of the second approach. Our calculations clearly demonstrated that the ring amino group absorbs at higher frequencies than the remaining three amino N-H protons of the protonated aminoethyl group, implying that the chemical bonding in the former group is stronger than in the three amino N-H bonds, thus forming weaker hydrogen bonding with the surrounding solvent molecules. In this way the results of the simulation complemented the experimental spectrum that cannot distinguish between the two sets of protons. The effects of deuteration were also considered. The resulting N-D absorption is narrower and red-shifted. The presented methodology is of general applicability to strongly correlated systems, and it is particularly tuned to provide computational support to vibrational spectroscopy. Perspectives are given for its future applications in computational studies of tunneling in enzyme reactive centers and for receptor activation.

Polycyclic croissant-like organic compounds are powerful superbases in the gas phase and acetonitrile--a DFT study.

A new type of the π-electron polycyclic organic superbases is proposed exhibiting very high proton affinities in the gas phase spanning the range from 280 to 323 kcal mol(-1) and the pK(a) up to 41.4 units in the MeCN solutions. Their salient feature is formation of the (H(+))-bridge upon protonation and a strong cationic resonance effect in the corresponding conjugate acids.

Polycyano derivatives of some organic tri- and hexacyclic molecules are powerful super- and hyperacids in the gas phase and DMSO: computational study by DFT approach.

B3LYP/6-311+G(2df,p)//B3LYP/6-31+G(d) calculations convincingly show that tricyclic organic compounds 1 and 2 offer scaffolds suitable for tailoring powerful neutral organic acids. Their cyanation at all C(sp(2))-H positions provide superacids as evidenced by their enthalpies of deprotonation ΔHacid(1bCN) = 257.2 and ΔHacid(2bCN) = 250.9 kcal mol(-1), which are close to the threshold of hyperacidity of 245 kcal mol(-1). On the other hand hexacyclic system 3 cyanated at all possible substitution sites along the perimeter except the acidic C(sp(3))-H position provides a true hyperacid with ΔHacid(3aCN) = 242.8 kcal mol(-1). The reason behind the dramatic acidifying effect is a vigorous anionic resonance effect in the corresponding conjugate bases assisted by a cooperative substituent effect of the CN groups. It is convincingly shown that compounds 1 and 2 represent rigid antiaromatic quasi-[12]annulene and aromatic quasi-[14]annulene par excellence, respectively, conforming to Hückel's (4n + 2)π electron count rule in the bridged polycyclic systems. Calculations of the pKa values in DMSO show that the polycyano derivatives are powerful superacids in solutions too.

Superbasicity of a bis-guanidino compound with a flexible linker: a theoretical and experimental study.

The bis-guanidino compound H(2)C{hpp}(2) (I; hppH = 1,3,4,6,7,8-hexahydro-2H-pyrimido[1,2-a]pyrimidine) has been converted to the monocation [I-H](+) and isolated as the chloride and tetraphenylborate salts. Solution-state spectroscopic data do not differentiate the protonated guanidinium from the neutral guanidino group but suggest intramolecular "-N-H...N=" hydrogen bonding to form an eight-membered C(3)N(4)H heterocycle. Solid-state CPMAS (15)N NMR spectroscopy confirms protonation at one of the imine nitrogens, although line broadening is consistent with solid-state proton transfer between guanidine functionalities. X-ray diffraction data have been recorded over the temperature range 50-273 K. Examination of the carbon-nitrogen bond lengths suggests a degree of "partial protonation" of the neutral guanidino group at higher temperatures, with greater localization of the proton at one nitrogen position as the temperature is lowered. Difference electron density maps generated from high-resolution X-ray diffraction studies at 110 K give the first direct experimental evidence for proton transfer in a poly(guanidino) system. Computational analysis of I and its conjugate acid [I-H](+) indicate strong cationic resonance stabilization of the guanidinium group, with the nonprotonated group also stabilized, albeit to a lesser extent. The maximum barrier to proton transfer calculated using the Boese-Martin for kinetics method was 2.8 kcal mol(-1), with hydrogen-bond compression evident in the transition state; addition of zero-point vibrational energy values leads to the conclusion that the proton transfer is barrierless, implying that the proton shuttles freely between the two nitrogen atoms. Calculations determining the gas-phase proton affinity and the pK(a) in acetonitrile both indicate that compound I should behave as a superbase. This has been confirmed by spectrophotometric titrations in MeCN using polyphosphazene references, which give an average pK(a) of 28.98 +/- 0.05. Triadic analysis indicates that the dominant term causing the high basicity is the relaxation energy.

The isomerization barrier in cyanocyclobutadienes: an ab initio multireference average quadratic coupled cluster study.

The energy profiles of the isomerization of mono, di-, and tetracyano-substituted cyclobutadienes (CBDs) are computed at the multireference average quadratic coupled cluster/complete active space self-consistent field level of theory. It was found that the energy barrier heights for the automerization reaction are 2.6 (tetracyano-CBD), 5.1 (1,3-dicyano-CBD), and 6.4 (cyano-CBD) kcal mol(-1), implying that they are lowered relative to that in the parent CBD (6.4 kcal mol(-1)), the monosubstituted derivative being an exception. Since the free CBD shuttles between two equivalent structures even at low temperature of 10 K, it follows that bond-stretch isomerism does not take place in cyanocyclobutadienes. Instead, these compounds exhibit rapid fluxional interconversion at room temperature between two bond-stretch isomers by the double bond flipping mechanism. The reason behind the decrease in the barrier heights is identified as a slightly enhanced resonance effect at the saddle points separating two (equivalent) bond-stretch isomers, compared to that in the equilibrium structures, predominantly due to the diradical character of the former. It is also shown that the energy gap between the singlet ground state saddle point structure and the first triplet equilibrium geometry decreases upon multiple substitution by the cyano groups. The splitting of the S and T energy is small being within the range of 6.5-8.2 kcal mol(-1).

Interpretation of Brønsted acidity by triadic paradigm: a G3 study of mineral acids.

Deprotonation enthalpies and the gas-phase acidities of 24 inorganic acids are calculated by using composite G3 and G2 methodologies. The computed values are in very good accordance with available measured data. It is found that the experimental DeltaH(acid) values of the FSO(3)H and CF(3)SO(3)H are too high by some 6 and 7 kcal mol(-1), respectively. Furthermore, a new DeltaH(acid) value for HClO(4) of 300 kcal mol(-1) is recommended and suggested as a threshold of superacidicity in the gas phase. The calculated deprotonation enthalpies are interpreted by employing the trichotomy paradigm. Taking into account that the deprotonation enthalpy is a measure of acidity, it can be safely stated that the pronounced acidities of mineral acids are to a very large extent determined by Koopmans' term with very few exceptions, one of them being H(2)S. To put it in another way, acidities are predominantly a consequence of the ability of the conjugate bases to accommodate the excess electron charge, since Koopmans' term in trichotomy analysis is related to conjugate base anion. The final state is decisive in particular for superacids like ClSO(3)H, CF(3)SO(3)H, HClO(4), HBF(4), HPF(6), HAlCl(4), and HAlBr(4). However, in the latter two molecules the bond dissociation energy of the halogen-H bond substantially contributes to their high acidity too. Therefore, acidity of these two most powerful superacids studied here is determined by cooperative influence of both initial and final state effects. It should be emphasized that acidity of hydrogen halides HCl and HBr is a result of concerted action of all three terms included in triadic analysis. A byproduct of the triadic analysis are the first adiabatic ionization energies of the anionic conjugate bases. They are in fair to good agreement with the experimental data, which are unfortunately sparse. A fairly good qualitative correlation is found between the gas-phase deprotonation enthalpies of six mineral O-H acids and available Hammett-Taft sigma(p)- constants of the corresponding substituent groups.

Hydride affinities of some substituted alkynes: prediction by DFT calculations and rationalization by triadic formula.

Hydride affinities (HAs) of the ethynes substituted by a wide range of different substituents are considered by using the B3LYP methodology. The computed values are in fair agreement with available experimental data, which are unfortunately scarce. The trend of changes of the HAs is rationalized by trichotomy formula. One of the important results of this analysis is a finding that similar HA values might result from completely different effects. Alternative sites of the H- attack are examined and the difference in energies relative to the most susceptible positions is interpreted. Structural features of substituted ethyne hydrides are briefly discussed.

Automerization reaction of cyclobutadiene and its barrier height: an ab initio benchmark multireference average-quadratic coupled cluster study.

The problem of the double bond flipping interconversion of the two equivalent ground state structures of cyclobutadiene (CBD) is addressed at the multireference average-quadratic coupled cluster level of theory, which is capable of optimizing the structural parameters of the ground, transition, and excited states on an equal footing. The barrier height involving both the electronic and zero-point vibrational energy contributions is 6.3 kcal mol(-1), which is higher than the best earlier theoretical estimate of 4.0 kcal mol(-1). This result is confirmed by including into the reference space the orbitals of the CC sigma bonds beyond the standard pi orbital space. It places the present value into the middle of the range of the measured data (1.6-10 kcal mol(-1)). An adiabatic singlet-triplet energy gap of 7.4 kcal mol(-1) between the transition state (1)B(tg) and the first triplet (3)A(2g) state is obtained. A low barrier height for the CBD automerization and a small DeltaE((3)A(2g),(1)B(1g)) gap bear some relevance on the highly pronounced reactivity of CBD, which is briefly discussed.

Clar's sextet rule is a consequence of the sigma-electron framework.

A number of condensed PAHs are examined to identify the underlying reasons governing empirical Clar's rule taking benzene as a limiting case. It is found that the so-called Clar's structures are the only minima on the MP2(fc) potential energy hypersurfaces, meaning that other conceivable valence isomers are nonexistent. The influence of the electron correlation energies to the stability of Clar's structures is substantial with predominating influence of the sigma-electrons. However, the contributions arising from the sigma- and pi-electron correlation energies are approximately the same, if Clar's structures are compared with some artificial pi-electron localized or graphite-like delocalized planar systems. Analysis of the Hartree-Fock (HF) energies provides a compelling evidence that the origin of stability of Clar's structures lies in a decrease of the positive T, V(ee) and V(nn) energy terms relative to some characteristic virtual "delocalized" or "localized" model geometries. Partitioning of the mixed and terms in the sigma- and pi-type contributions, by using the stockholder (SHR), equipartitioning (EQP) and standard pi (SPI) schemes, unequivocally shows that the driving force leading to Clar's structures are more favorable sigma-type interactions. All these conclusions hold for the archetypal benzene too, which could be considered as a limiting Clar system. Finally, the boundaries of Clar's hypothesis and some common misconceptions are briefly discussed. Perusal of the geometric parameters and pi-bond orders reveals that there are no benzene rings completely "vacant" or "fully occupied" by the pi-electrons, envisaged by Clar in his picture of condensed benzenoid compounds. Instead, there are six-membered rings with higher and lower total pi-electron density. The bond length anisotropy of the former rings is smaller. It is concluded that Clar's proposition is a useful rule of thumb providing qualitative information on the stability of the PAH systems, which in turn should not be overinterpreted.

High basicity of phosphorus-proton affinity of tris-(tetramethylguanidinyl)phosphine and tris-(hexamethyltriaminophosphazenyl)phosphine by DFT calculations.

It is shown by approximate but reliable DFT calculations that the title compounds represent very strong superbases in gas phase and MeCN. In particular, tris-(hexamethyltriaminophosphazenyl)phosphine has a proton affinity, PA, of 295.5 kcal mol(-1) and records a pKa(MeCN) of 50 +/- 1 units.

1,8-Bis(hexamethyltriaminophosphazenyl)naphthalene, HMPN: a superbasic bisphosphazene "proton sponge".

It is shown that a combination of Schwesinger's phosphazene base concept and the idea of the disubstituted 1,8-naphthalene spacer, first introduced by Alder in paradigmatic 1,8-bis(dimethylamino)naphthalene (DMAN), yields a new superbase, HMPN, which represents the up to date most basic representative of this class of "proton sponges", as evidenced by the theoretically estimated proton affinity PA = 274 kcal/mol and the measured pK(BH+) (MeCN) 29.9 +/- 0.2. HMPN is by nearly 12 orders of magnitude more basic than Alder's classical 1,8-bis(dimethylamino)naphthalene (DMAN). The title compound, HMPN, is prepared and fully characterized. The spatial structure of HMPN and its conjugate acid is determined by X-ray technique and theoretical DFT calculations. It is found that monoprotonated HMPN has an unsymmetrical intramolecular hydrogen bridge (IHB). This cooperative proton chelating effect renders the bisphosphazene more basic than Schwesinger's set of "monodentate" P1 phosphazene bases. The density functional calculations are in good accordance with the experimental results, providing some complementary information. They conclusively show that the high basicity of HMPN is a consequence of the high energy content of the base in its initial neutral state and the intramolecular hydrogen bonding in the resulting conjugate acid with contributions to proton affinity of 14.1 and 9.5 kcal/mol, respectively.

Extremal acidity of Rees polycyanated hydrocarbons in the gas phase and DMSO--a density functional study.

It is shown by using the density functional theory (DFT) calculations that Rees tricyclic[10]annulene 1 and its benzo-annelated derivative 2, substituted by CN groups at all peripheral sp2 carbon positions, represent hyperstrong neutral superacids in the gas-phase and DMSO.

Hydride affinities of borane derivatives: novel approach in determining the origin of lewis acidity based on triadic formula.

The problem of intrinsic Lewis acidities of simple boron compounds (BH3-mXm, m = 0-3, X = F, Cl, Br, CH3, and OH) is assessed by their gas-phase hydride affinities (HAs). A simple and intuitively appealing picture of the interaction process including detachment of an electron from the hydride ion H-, capture of the pruned electron to the investigated Lewis acid (LA), and subsequent formation of the homolytic chemical bond between two newly created radicals is proposed. It enables transparent and straightforward dissection of the initial and final state effects, which taken together with the intermediate relaxation stabilization determine the trend of changes in the hydride affinities. The former effect is reflected in the electron affinities of the neutral Lewis acids given within Koopmans' approximation, while the final state effect involves properties of the formed Lewis acid-base adducts mirrored in the bond dissociation energy of the formed [LA-H]- chemical bond. It is demonstrated that unexpectedly low Lewis acidity of fluoroboranes relative to the corresponding chlorine and bromine derivatives can be traced down to the unfavorable Koopmans' electron affinities. Hence, it is a consequence of the initial state effect. In contrast, chloroboranes are more potent Lewis acids than fluoroboranes, because the relaxation and final state effects decisively influence their Lewis acidity. Finally, bromine-substituted borane compounds provide the most powerful studied Lewis acids. Their hydride affinities are result of a synergic interplay of the initial state, intermediate stabilization via relaxation, and final state effects. It is shown that Pearson's global hardness indices defined within his hard and soft acid-base (HSAB) principle fail to adequately predict and interpret the calculated hydride affinities.

Periodic trends in bond dissociation energies. A theoretical study.

Bond dissociation energies (BDEs) of all possible A-X single bonds involving the first- and second-row atoms, from Li to Cl, where the free valences are saturated by hydrogens, have been estimated through the use of the G3-theory and at the B3LYP/6-311+G(3df,2pd)//B3LYP/6-31G(2df,p) DFT level of theory. BDEs exhibit a periodical behavior. The A-X (A = Li, Be, B, Na, Mg, Al, and Si) BDEs show a steady increase along the first and the second row of the periodic table as a function of the atomic number Z(X). For A-X bonds involving electronegative atoms (A = C, N, O, F, P, S, and Cl) the bond energies achieve a maximum around Z(X) = 5. The same behavior is observed when BDEs are plotted against the electronegativity chi(X) of the atom X. Thus, for A-X bonds (A = Li, Be, B, Na, Mg, Al, Si), the BDEs for a fixed A increases, grosso modo, as the electronegativity differences between X and A increase, with some exceptions, which reflect the differences in the relaxation energies of the radicals produced upon the bond cleavage. A similar trend, albeit less pronounced, is found for single A-X bonds, where A = C, N, O, F, P, S, and Cl. However, there is an additional feature embodied in the enhancement of the strength of the A-boron bonds due to the ability of boron to act as a strong electron acceptor. The trends in bond lengths and charge densities at the bond critical points are in line with the aforementioned behavior.

Gas-phase structure of protonated histidine and histidine methyl ester: combined experimental mass spectrometry and theoretical ab initio study.

Gas-phase H/D exchange experiments with CD3OD and D2O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp2) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol(-1) for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol(-1) lower than the reported experimental value.

A novel approach in analyzing aromaticity by homo- and isostructural reactions: an ab initio study of fluorobenzenes.

The influence of fluorine substitutions on the stability of benzene is examined by using the Hartree-Fock (HF) and MP2 models. It is conclusively demonstrated that homodesmotic reactions based on the open-chain zigzag polyenes are unsatisfactory. A comparison of the intramolecular interactions of educts and products shows that they are not well balanced. Hence, these reactions should be abandoned in discussing aromaticity. A much better vehicle for exploring aromaticity is provided by homostructural reactions, which employ cyclic monoene and diene as reference model compounds. Their heavy atoms are enforced to assume planar geometries to enable sigma/pi separation. The HF/cc-pVTZ calculations show that extrinsic aromaticity of benzene B DeltaE(ease)(B)() arises both from the sigma- and pi-contributions. They are -14.8 and -23.1 in kcal/mol, respectively, if the stockholder energy partitioning scheme is employed. This result implies that both the sigma- and pi-frameworks contribute to the aromatic stabilization of B, the latter being more important. The total aromatic stabilization DeltaE(ease)(B)() is -37.9 kcal/mol. Schleyer's indene-isoindene isomerization approach also strongly indicates that the decisive factor in determining the aromatic stability of the benzene moiety is the pi-electron framework. The origin of extrinsic aromaticity is identified as the increased nuclear-electron attraction of both sigma- and pi-electrons, if 1,3-cyclohexadiene is used as a gauge compound. Further, by using a system of isostructural reactions, it is conclusively demonstrated that fluorobenzenes exhibit a remarkable additivity of the substituent effects, as far as the stability of multiply substituted benzenes is concerned. This additivity rule is so accurate that it enables delineation of the fluorine repulsions and the aromaticity defect DeltaE(AD). It appears that the DeltaE(AD) values increase upon sequential fluorine substitution at the next nearest (vicinal) position thus making multiply fluorinated benzenes less stable.