Current Organic Chemistry - Volume 17, Issue 23, 2013

The ability to derive colored representations of widely employed distance-based topological indices from chemical reactivity electronegativity and chemical hardness has been developed in the novel theoretical tool presented in this work to provide novel, meaningful topo-reactive or structure-reactivity indices with application to polycyclic aromatic hydrocarbons (PAHs). The model, which combines topological and ab initio molecular structural information, relies on the so-called Timisoara-Parma rule for assigning the axial distribution of electronegativity and chemical hardness to a given molecular structure based on a compact finite-difference (CFD) hierarchy, which involves ordering nine forms of electronegativity and chemical hardness derivative-based definitions within conceptual density functional theory (DFT). The results are in good agreement with theoretical and experimental properties improving the predictive power of standard topological indices. The proposed method is suitable for molecular structures with delocalized electrons.

The successful synthesis of different polyacenes including theoretical assessment on the stability of larger acenes are discussed. The existence of favorable aromaticity criterion in polyacenes is understood in terms of different aromaticity indicators like nucleus independent chemical shift (NICS), harmonic oscillator model of aromaticity (HOMA), bond resonance energy (BRE). Clar's Π- sextet rule is also very much effective in explaining their aromaticity. By virtue of low HOMO-LUMO gap, the probable application of polyacenes in the field of organic electronics is also highlighted. The polyacene analogues of inorganic ring compounds, viz., BN-acenes, CN-acenes, BO-acenes, BS-acenes, AlN-acenes and of alkali ring compounds, viz., Na-acenes and K-acenes also have polyacene-like aromaticity although in few cases the origin of aromaticity and qualitative nature of aromaticity differ significantly.

Due to the current increasing interest in extended nanosystems, such as fullerenes and graphenes, based on fundamental organic systems, polycyclic aromatic hydrocarbons (PAHs) have been recognized as highly important structures. PAHs are important because they comprise a benchmark structure for iteratively generating nanostructures and directly produce metabolites with a toxicological impact that has not been discerned in our post-industrial global era. Moreover, PAHs are the primary carbon structures in interstellar dust clouds, according to recent data from astrophysical and exochemical studies. The work herein presents each aspect from a synthetic perspective; PAHs are analyzed by illustrating the PAH chemical-biological interaction mechanism driven by chemical reactivity indices (electronegativity, chemical hardness, and related characteristics, such as electrophilicity and chemical power). Both the gas phase and partially de-bonding active space (related to Simplified Molecular Input Line Entry System - SMILES) structures are employed. We used Quantitative Structure-Activity Relationships (QSAR) analysis to show that the latter better correlates with the available lipophilicity (considered herein using the computed LogP, which is the octanol-water partition coefficient) by measuring the propensity for diverse PAHs towards cellular wall transduction.

Polycyclic Aromatic Hydrocarbons (PAHs) have been the focus of great attention for a long time owing to their impact on public health and the environment. In this article we overview various QSAR studies on PAHs and some derivatives, that have been developed during the last decade by different authors. Several properties of broad interest are analyzed, such as carcinogenesis, mutagenicity, biocatalytic oxidation, phototoxicity, dermal penetration, biodegradation, and others. The molecular descriptors types and modeling techniques used are briefly commented.

The central nervous system is endowed with complex mechanisms of defense. However, these protection mechanisms fail in the presence of risk factors such as genetic mutations, environmental factors (bisphenol A, polycyclic aromatic hydrocarbons (PAHs), polyfluoroalkyl chemicals) or social stress and psychiatric disorders (anxiety, depression, psychosis, attention deficits) appear. Critical psychiatric conditions treatment consists in administration of antidepressants and antipsychotics drugs. These drugs are widely prescribed, but their efficiency in controlling mental symptoms is an important point in current clinical studies. Antidepressants and antipsychotics register several side effects and their interactions with other polycyclic aromatic hydrocarbons are well established. Research is focused upon reducing these side effects and understanding their pharmacodynamic and pharmacokinetic properties in order to develop advanced methods to predict induced pharmacological events. Here we intend to detail recent advances in the field of structure-activity relationship (QSAR) applied to antidepressants and antipsychotics with polycyclic aromatic structure as last generation drugs used in central nervous system disorders. We present the biological activity of large series of psychiatric drugs predicted by 2D and 3D-QSAR dependent and independent molecules alignment. Predicted biological activities were correlated with common pharmaceutical descriptors as steric, electronic hydrogen donor/acceptor bond but also new components of QSAR models as membrane ions’ contributions to the antagonism of these drugs at membrane receptors are presented. The paper refers both to preclinical tested molecules and to already known antidepressants and antipsychotics based on a large variety of polycyclic aromatic structure. Drug potency decrease in the presence of PAHs is also discussed.

Mass spectrometry (MS) is one of the key analytical technology on which the emerging “-omics” approaches are based. It may provide detection and quantization of thousands of proteins and biologically active metabolites from a tissue, body fluid or cell culture working in a “global” or “targeted” manner, down to ultra-trace levels. It can be expected that the high performance of MS technology, coupled to routine data handling, will soon bring fruit in the request for a better understanding of human diseases, leading to new molecular biomarkers, hence affecting drug targets and therapies. metabolomics fields, up to the most recent MS applications to meta-omic studies. In this review, we focus on the main advances in the MS technologies, influencing genomics, transcriptomics, proteomics, lipidomics and metabolomics fields, up to the most recent MS applications to meta-omic studies.

Ytterbium triflate, Yb(OTf)3, is a versatile Lewis acid that has high catalytic activity in many organic reactions, including aldol, Michael, Mannich, Friedel-Crafts, Diels-Alder, and some other types of reactions. Less than 10 mol% of Yb(OTf)3 is normally sufficient for most organic transformations and can be recovered and re-used without loss of catalytic activity. In addition, Yb(OTf)3 is very stable and its catalyzed reactions can be carried out in both organic solvents and aqueous conditions.

Rapid and efficient methods using no-carried-added [¹⁸F]fluoride as the source of fluorine-18 for nucleophilic aromatic fluorination play an important role in the development of new radiopharmaceuticals for positron emission tomography (PET). Molecules that bear electron-rich aromatic moieties are especially difficult to label by direct single-step nucleophilic no-carrier-added radiofluorination. Classical Balz-Schiemann reaction with its modifications, Wallach reaction and diaryliodonium salts methodology are a few methods to enable this. The present review provides a critical overview of these chemical methods with the emphasis on diaryliodonium salt as precursors for the direct introduction of [¹⁸F]fluoride into electron-rich arenes in synthesis of ¹⁸F-labeled molecules for PET scanning.