How Molecular Topology Can Help in Amyotrophic Lateral Sclerosis (ALS) Drug Development: A Revolutionary Paradigm for a Merciless Disease

Even if amyotrophic lateral sclerosis is still considered an orphan disease to date, its prevalence among the population is growing fast. Despite the efforts made by researchers and pharmaceutical companies, the cryptic information related to the biological and physiological onset mechanisms, as well as the complexity in identifying specific pharmacological targets, make it almost impossible to find effective treatments. Furthermore, because of complex ethical and economic aspects, it is usually hard to find all the necessary resources when searching for drugs for new orphan diseases. In this context, computational methods, based either on receptors or ligands, share the capability to improve the success rate when searching and selecting potential candidates for further experimentation and, consequently, reduce the number of resources and time taken when delivering a new drug to the market. In the present work, a computational strategy based on Molecular Topology, a mathematical paradigm capable of relating the chemical structure of a molecule to a specific biological or pharmacological property by means of numbers, is presented. The result was the creation of a reliable and accessible tool to help during the early in silico stages in the identification and repositioning of potential hits for ALS treatment, which can also apply to other orphan diseases. Considering that further computational and experimental results will be required for the final identification of viable hits, three linear discriminant equations combined with molecular docking simulations on specific proteins involved in ALS are reported, along with virtual screening of the Drugbank database as a practical example. In this particular case, as reported, a clinical trial has been already started for one of the drugs proposed in the present study.

Computing Edge Metric Dimension of One-Pentagonal Carbon Nanocone

Minimum resolving sets (edge or vertex) have become an integral part of molecular topology and combinatorial chemistry. Resolving sets for a specific network provide crucial information required for the identification of each item contained in the network, uniquely. The distance between an edge e = cz and a vertex u is defined by d(e, u) = min{d(c, u), d(z, u)}. If d(e1, u) ≠ d(e2, u), then we say that the vertex u resolves (distinguishes) two edges e1 and e2 in a connected graph G. A subset of vertices RE in G is said to be an edge resolving set for G, if for every two distinct edges e1 and e2 in G we have d(e1, u) ≠ d(e2, u) for at least one vertex u ∈ RE. An edge metric basis for G is an edge resolving set with minimum cardinality and this cardinality is called the edge metric dimension edim(G) of G. In this article, we determine the edge metric dimension of one-pentagonal carbon nanocone (1-PCNC). We also show that the edge resolving set for 1-PCNC is independent.

Molecular Topology for the Search of New Anti-MRSA Compounds

The variability of methicillin-resistant Staphylococcus aureus (MRSA), its rapid adaptive response against environmental changes, and its continued acquisition of antibiotic resistance determinants have made it commonplace in hospitals, where it causes the problem of multidrug resistance. In this study, we used molecular topology to develop several discriminant equations capable of classifying compounds according to their anti-MRSA activity. Topological indices were used as structural descriptors and their relationship with anti-MRSA activity was determined by applying linear discriminant analysis (LDA) on a group of quinolones and quinolone-like compounds. Four extra equations were constructed, named DFMRSA1, DFMRSA2, DFMRSA3 and DFMRSA4 (DFMRSA was built in a previous study), all with good statistical parameters, such as Fisher–Snedecor F (>68 in all cases), Wilk’s lambda (<0.13 in all cases), and percentage of correct classification (>94% in all cases), which allows a reliable extrapolation prediction of antibacterial activity in any organic compound. The results obtained clearly reveal the high efficiency of combining molecular topology with LDA for the prediction of anti-MRSA activity.

Rational Construction of Organic Electronic Devices Based on S-Indacene Fragments

<pre>Herein, we report the computational investigation of s-indacene as a viable candidate for the construction of organic electronic devices. <br>We also investigate the effect of molecular topology on the frontier energy levels of the s-indacene fragments and the possibility of <br>tuning the frontier energy levels by a rational choice of substituents and bridging groups. The rationale behind the choice of s-indacene <br>fragments as the basis for the construction of 2D organic electronic devices with tailor-made properties can be extended towards the construction <br>of other 2D covalent organic frameworks with applications in organic electronics and spintronics.</pre>

Rational Construction of Organic Electronic Devices Based on S-Indacene Fragments

<pre>Herein, we report the computational investigation of s-indacene as a viable candidate for the construction of organic electronic devices. <br>We also investigate the effect of molecular topology on the frontier energy levels of the s-indacene fragments and the possibility of <br>tuning the frontier energy levels by a rational choice of substituents and bridging groups. The rationale behind the choice of s-indacene <br>fragments as the basis for the construction of 2D organic electronic devices with tailor-made properties can be extended towards the construction <br>of other 2D covalent organic frameworks with applications in organic electronics and spintronics.</pre>

Post-synthetic modification of supramolecular assemblies of β-diketonato Cu(ii) complexes: comparing and contrasting the molecular topology by crystal structure and quantum computational studies

Solvent-induced structural transformations on the metal coordination sphere in homoleptic (1 and 2) and heteroleptic (3 and 4) Cu(ii) complexes were analyzed and investigated by crystallographic and quantum computational studies.

Unraveling topology-induced shape transformations in dendrimersomes

Using cell-mimetic dendrimersomes we demonstrated how changes in the molecular topology of the amphiphilic Janus dendrimers forming the bilayer lead to the evolution of shape without the need for any active cellular machinery.