Slavko Radenković

Correlations between local aromaticity indices of bipartite conjugated hydrocarbons.

Local aromaticity in rings of conjugated hydrocarbons can be measured in a variety of ways. In the present paper, we concentrate on two of these, namely, EC, i.e., the pi-electron content or pi-electron partition, and ef, the energy effect of cycles. For the central ring in five bipartite conjugated hydrocarbons (anthracene, triphenylene, perylene, coronene, and biphenylene), it was found that EC and ef values are modified in a consistent and predictable manner by annelation with benzenoid rings. Equations are presented for computing EC and ef values for the central ring in terms of three integers representing the numbers of annelated benzenoid rings (A, L, and G for angular, linear, and geminal annelation, respectively). The coefficients of A and G are positive (A > G) and the coefficient of L is negative for benzenoids, but for biphenylene, the situation is reversed for coefficients in the correlation for ef values.

How does aromaticity rule the thermodynamic stability of hydroporphyrins

Several measures of aromaticity including energetic, magnetic, and electron density criteria are employed to show how aromatic stabilization can explain the stability sequence of hydroporphyrins, ranging from porphin to octahydroporphin, and their preferred hydrogenation paths. The methods employed involve topological resonance energies and their circuit energy effects, bond resonance energies, multicenter delocalization indices, ring current maps, magnetic susceptibilities, and nuclear-independent chemical shifts. To compare the information obtained by the different methods, the results have been put in the same scale by using recently proposed approaches. It is found that all of them provide essentially the same information and lead to similar conclusions. Also, hydrogenation energies along different hydrogenation paths connecting porphin with octahydroporphin have been calculated with density functional theory. It is shown by using the methods mentioned above that the relative stability of different hydroporphyrin isomers and the observed inaccessibility of octahydroporphin both synthetically and in nature can be perfectly rationalized in terms of aromaticity.

Effect of benzo-annelation on local aromaticity in heterocyclic conjugated compounds.

The effect of benzo-annelation on the local aromaticity of the central ring of acridine (1), 9H-carbazole (2), dibenzofuran (3), and dibenzothiophene (4) was analyzed by means of the energy effects (ef), pairwise energy effects (pef), multicenter delocalization index (MCI), electron density at ring critical points (ρ(r(C))), harmonic oscillator model of aromaticity (HOMA), and nucleus independent chemical shifts (NICS). According to energetic, electron delocalization, and geometrical indices, angular benzo-annelation increases, whereas linear benzo-annelation decreases, the extent of the local aromaticity of the central ring containing heteroatoms. The local aromaticity of the central heterocyclic ring in the examined molecules can significantly vary by applying different modes of benzo-annelation. The NICS values do not always support the results obtained by the other aromaticity indices and, in some cases, lead to completely opposite conclusions.

Ring currents in polycyclic sodium clusters

In the recent work by Khatua et al. (Khatua, S.; Roy, D. R.; Bultinck, P.; Bhattacharjee, M.; Chattaraj, P. K. Phys. Chem. Chem. Phys.2008, 10, 2461-2474) the synthesis and structure of a fac-trioxo molybdenum metalloligand and its sodium complex containing 1D hexagonal chains of sodium ions was reported. In the same paper, the aromaticity of hexagonal Na clusters was quantified by means of the nucleus-independent chemical shift and electronic multicenter indices. It was shown that the aromaticity of hexagonal Na-clusters is of the same order as the aromaticity of analogous benzenoid hydrocarbons. In the present study current density maps are used to rationalize the aromaticity of polycyclic Na clusters. It is shown that although polycyclic Na systems sustain a diatropic ring current, the induced current density is several times weaker than in analogous benzenoid hydrocarbons. A detailed analysis indicates that the current density in hexagonal Na systems is almost completely determined by four HOMO σ electrons.

Estrada Index of Benzenoid Hydrocarbons

A structure-descriptor EE, recently proposed by Estrada, is examined. If λ1, λ2, . . . ,λn are the eigenvalues of the molecular graph, then . In the case of benzenoid hydrocarbons with n carbon atoms and m carbon-carbon bonds, EE is found to be accurately approximated by means of the formula a1 n cosh (√2m/n)+a2, where a1 ≈ 1.098 and a2 = −0.64 are empirically determined fitting constants. Within classes of benzenoid isomers (which all have equal n and m), the Estrada index is linearly proportional to the number of bay regions.

Ring Currents in Benzo- and Benzocyclobutadieno-Annelated Biphenylene Derivatives

The effect of benzo and benzocyclobutadieno annelation on the current density induced in a series of biphenylene derivatives is examined at the B3LYP/cc-pVDZ level of theory, by using the CTOCD-DZ method. Angular benzo annelation increases, whereas linear benzo annelation decreases the intensity of paratropic (antiaromatic) current density along the four-membered ring of biphenylene. The opposite effect is found for benzocyclobutadieno annelation. It is shown that the extent of local aromaticity of the four-membered ring in biphenylene congeners can vary from highly antiaromatic to nonaromatic, as a result of different modes of annelation.

DFT study on singlet diradical character of zethrenes

The diradical character of zethrenes was investigated using a symmetry-broken UB3LYP/6-311G(d,p) method. The number of hexagons in the investigated molecules ranges from 6 to 12. It was found that all zethrenes are singlet diradicals, whose diradical character increases with the increasing size of the molecules. A singlet diradical structure provides a possibility for an electron pair to occupy different parts of space, and allows for achieving aromatic stabilization. It can be predicted, on the basis of the singlet-triplet values, that even higher zethrenes will be singlet, but not triplet molecules.

Aromaticity of closed-shell charged polybenzenoid hydrocarbons.

The aromatic stabilization of closed-shell charged polybenzenoid hydrocarbons (PBHs) has been scrutinized by means of energetic and magnetic aromaticity criteria and by direct measures of electron delocalization. Thus, topological resonance energies and their circuit contributions, ring current maps, and multicenter delocalization indices have been calculated for a series of 18 polybenzenoid cations containing from 3 to 10 benzene rings. All calculations indicate that the closed-shell cations have a similar degree of aromaticity compared to that of the corresponding closed-shell neutral PBHs. All cations investigated display a large degree of electronic delocalization in the ring, accompanied by significant aromatic stabilization and a strong diatropic peripheral electron current. Graph theoretical models describe perfectly the aromatic features of these hydrocarbon fragments, showing how they can be understood as a superposition of specific neutral PBHs. The large aromatic character of these systems suggests they may be relatively stable upon formation at combustion conditions, like those given in the interstellar medium. It has been postulated that closed-shell fragments of PBHs may play an important role in the photoluminescent phenomenon known as extended red emission.

Importance of hydrogen bonding and aromaticity indices in QSAR modeling of the antioxidative capacity of selected (poly)phenolic antioxidants

The quantitative structure-activity relationship (QSAR) models for predicting antioxidative capacity of 21 structurally similar natural and synthetic phenolic antioxidants was considered. The one-, two- and three-descriptor QSAR models were developed. For this purpose the literature data on the vitamin C equivalent antioxidative capacity (VCEAC) values were used as experimental descriptor of antioxidative capacity. Some thermodynamic and aromaticity properties, as well as the natural bond analysis (NBO) based quantities aimed at measuring the strength of intramolecular hydrogen bonds, were used as independent variables. It was examined whether a combination of these variables can yield a mathematical function that is in good correlation with the VCEAC values. It was shown that a combination of a certain thermodynamic descriptor (related to the single proton loss electron transfer mechanism) with the NBO-based quantities results in several two-descriptor models with the correlation coefficient greater than 0.950. Thus, a significant influence of internal hydrogen bonds on the antioxidative capacity of the studied molecules was confirmed. The best correlation with the VCEAC values was achieved within a three-descriptor QSAR model. This model was obtained by including a magnetic aromaticity index. It was found that aromaticity has only secondary effects on the antioxidative capacity.

Mononuclear gold(III) complexes with phenanthroline ligands as efficient inhibitors of angiogenesis: A comparative study with auranofin and sunitinib

Gold(III) complexes with 1,7- and 4,7-phenanthroline ligands, [AuCl3(1,7-phen-κN7)] (1) and [AuCl3(4,7-phen-κN4)] (2) were synthesized and structurally characterized by spectroscopic (NMR, IR and UV-vis) and single-crystal X-ray diffraction techniques. In these complexes, 1,7- and 4,7-phenanthrolines are monodentatedly coordinated to the Au(III) ion through the N7 and N4 nitrogen atoms, respectively. In comparison to the clinically relevant anti-angiogenic compounds auranofin and sunitinib, gold(III)-phenanthroline complexes showed from 1.5- to 20-fold higher anti-angiogenic potential, and 13- and 118-fold lower toxicity. Among the tested compounds, complex 1 was the most potent and may be an excellent anti-angiogenic drug candidate, since it showed strong anti-angiogenic activity in zebrafish embryos achieving IC50 value (concentration resulting in an anti-angiogenic phenotype at 50% of embryos) of 2.89μM, while had low toxicity with LC50 value (the concentration inducing the lethal effect of 50% embryos) of 128μM. Molecular docking study revealed that both complexes and ligands could suppress angiogenesis targeting the multiple major regulators of angiogenesis, such as the vascular endothelial growth factor receptor (VEGFR-2), the matrix metalloproteases (MMP-2 and MMP-9), and thioredoxin reductase (TrxR1), where the complexes showed higher binding affinity in comparison to ligands, and particularly to auranofin, but comparable to sunitinib, an anti-angiogenic drug of clinical relevance.