Zvonimir B. Maksić

The proton affinity of the superbase 1,8-bis(tetramethylguanidino)naphthalene (TMGN) and some related compounds: a theoretical study.

The spatial and electronic structure of the very strong neutral organic bases bis(tetramethylguanidino)naphthalene (TMGN), 4,5-bis(tetramethylguanidino)fluorene (TMGF) and some related compounds are explored by ab initio computational methods. Their affinity towards the proton is scrutinized both in the gas phase and in solution in acetonitrile. The protonation at the most basic center (the imine nitrogen) yields asymmetric and relatively strong intramolecular hydrogen bonds (IHB). It is found that the angular strain effect and steric repulsion practically vanish in TMGN which implies that its high absolute proton affinity (APA) has its origin in the inherent basicity of the guanidine fragment and a relatively strong IHB in [TMGN]H(+). The nonbonded repulsions in TMGF are higher than in TMGN, which in conjunction with a slightly stronger IHB in the corresponding conjugate acid makes it more basic: APA(TMGF)>APA(TMGN). An interesting new phenomenon is observed in both TMGN and TMGF: the proton triggers the resonance stabilization not only in the directly bonded guanidine moiety, but also in the other guanidine fragment which is more distant from the proton, albeit in a less pronounced manner. The latter feature is termed a partial protonation. This supports the hydrogen bonding and contributes to the IHB stabilization. Convincing evidence is presented that the solvent effect in acetonitrile is determined by two antagonistic factors: 1) the intrinsic (gas phase) proton affinity and 2) the size effect which is given by the ratio between the positive charge in molecular cation (conjugate acid) and the magnitude of the molecular surface. The resulting pK(a) values are given by an interplay of these factors.

Advances in determining the absolute proton affinities of neutral organic molecules in the gas phase and their interpretation: a theoretical account.

A magnificent edifice called acid/base chemistry is rooted in a single proton, small in size but of enormous importance. The upper floors of this building are reserved for biochemistry, while the penthouse belongs to life science. The edifice will grow into a sky scraper-like in the 21st century. Evidence provided by this Review shows that the coalescence of experimental and theoretical/computational work is not only highly desirable for that purpose, but, in fact, greatly needed.

Towards the absolute proton affinities of 20 α-amino acids

The absolute proton affinities (APA) of 20 α-amino acids, as obtained by the MP2(fc)/6-311+G∗∗//HF/6-31G∗ + ZPVE(HF/6-31G∗) and the scaled Hartree–Fock (HFsc) models, are presented. It is shown that the α-NH2 group is protonated in all but four cases: lysine (K), proline (P), histidine (H), and arginine (R). There is a good overall agreement with experimental data measured by the kinetic method. However, there are some notable exceptions such as glutamine (Q) and lysine (K), where strong hydrogen bonds in the protonated forms occur. It is suggested that the present results and theoretical models employed could be useful for resolving such experimental ambiguities. Furthermore, it appears that the HFsc model provides an efficient tool for elucidating APAs of artificial α-AAs, derivatives of natural α-AAs and their oligomers.

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.

Basicity of exceedingly strong non-ionic organic bases in acetonitrile —Verkade's superbase and some related phosphazenes

The basicity of Verkades superbase (12) in MeCN solution is considered by a quite accurate theoretical model. It is shown that the corresponding pKa value is 29.0. Hence, its basicity is comparable or higher than that of some other P1 phosphazenes, but it is lower than the basicity of P2 phosphazenes. Structural characteristics of Verkades superbase and its conjugate acid, as well as the origin of its pronounced basicity, are briefly discussed. Extended Verkades superbase 13 and some Janus-type phosphazenes are examined too. It is shown that they are very good candidates for even stronger neutral organic superbases. A very useful by-product of the present study are quite accurate estimates of the gas phase proton affinities of some P1, P2, P3 and P4 polyaminophosphazenes obtained by the B3LYP/6-311+G(2df,p)//B3LYP/6-31G* scheme. The latter was successfully tested against G2 results on small molecules. This is of importance, because the experimentally measured gas phase values for phosphazenes are not available, implying that the theoretical data fill this gap with reliable information.

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.

Basicity of organic bases and superbases in acetonitrile by the polarized continuum model and DFT calculations

The basicities of a large number of organic bases and superbases, including nitrogen basic centers in various chemical environments occurring in phosphazenes, amidines, amines, anilines and pyridines, have been studied in acetonitrile by the isodensity polarized continuum model employing two DFT computational schemes differing in the basis sets for final single-point calculations. It turned out that the B3LYP/6-311+G(d,p)//B3LYP/6-31G(d) method serves the purpose giving good agreement for basicities with experiment for both gas phase and acetonitrile solutions treating widely different bonding situations of basic nitrogen atoms on an equal footing. An attempt is made to correlate the experimental pKa(MeCN) values with the proton affinities (PA) in MeCN. The results are less accurate than those achieved by using basicities in acetonitrile. In particular, the PA(MeCN)s frequently failed in reproducing the pKa(MeCN) values in systems possessing multiple intramolecular hydrogen (IMH) bonds formed via corona effects. In such cases the use of basicities is mandatory instead. A useful corollary of these calculations on systems with multiple IMH bonds is that comparison of the theoretical and experimental pKa values can provide an insight into the structure of the most stable conformations in solutions.

Computer aided design of organic superbases: the role of intramolecular hydrogen bonding

The role of intramolecular hydrogen bonding (IMHB) in determining the proton affinities and basicities of some bis(tetramethylguanidine)systems was examined. For this purpose a series of molecular backbone moieties serving as carriers of the bis(tetramethylguanidine)crowns were explored. It was found that the best backbones are provided by phenanthrene and 9,10-dihidrophenanthrene, giving rise to proton affinities as large as 268.2 and 266.8 kcal mol1−, respectively. The corresponding pKa values in acetonitrile are 29.0 and 28.8, implying that these two compounds [6(bs)and 5(bs)] are candidates for powerful superbases. Their intramolecular hydrogen bond strengths are ≈19 kcal mol1−, which result inter alia from the partial protonation of the vis-a-vis guanidine group.

Theoretical calculations of proton affinities in phenol

Abstract It is shown that a relatively simple MP2(fc)/6–31G ∗∗ //HF/6–31G ∗ model is capable of providing quantitative description of protonation in phenol. The use of the 6–31G ∗∗ basis set in the single-point MP2 calculation is crucial in this respect. The zero-point energy (ZPE) contribution to the proton affinity (PA) is estimated at the HF/6–31G ∗ level of approximation. It appears that the contribution of the ZPE energy to relative ΔPA proton affinities is negligible. The simple additivity rule for calculating empirical ZP energies works relatively well for the protonated species too. The energetically most favourable site of the proton attack is para to the OH substitution in accordance with the experimental finding. Performance of the MP2(fc)6–31G ∗∗ +ZPE(HF/6–31G ∗ ) model in reproducing protonation at the oxygen atom is tested in some medium size alcohols and ethers. The calculated PA values are in good agreement with the measured data.

In search of neutral organic superbases—iminopolyenes and their amino derivatives

The intrinsic proton affinities of iminopolyenes and their amino derivatives are considered. It is shown that substitution of amino groups at strategic positions increases proton affinity (PA) to superbasic values particularly in branched polyenes. It follows that the number of double bonds, selection of the conformations and a judicious choice of substituents offer a closely spaced ladder of highly basic compounds spanning the range of values of PAs between 206.5 and 271.9 kcal mol−1, which might be of some importance in acid–base chemistry. This conclusion is strengthened by the fact that several of the studied amino derivatives of iminopolyenes exhibit very high pKa values between 30.0–33.5 in acetonitrile. Hence, they qualify as candidates for powerful neutral organic superbases.