Meta Position Research Articles

Synthesis and Characterization of Novel 4-aryl-4H-chromene Derivatives Using Borax and Evaluation of their Anticancer Effects.

4-aryl-4H-chromenes have attracted attention as potential anticancer agents. In an effort to discover effective compounds, we designed a new series of these chromenes with methoxy substitution at 2, 3, 4, 5, and 6 positions. The synthesized compounds were tested for anticancer properties against two human cancer cell lines (MCF-7 and PC3) as well as a normal cell line. The MTT assay showed that the 5g derivative, with methoxy groups at ortho and meta positions, exhibited the highest potency (IC50 = 40 µM) against the PC3 cell line. Furthermore, induction of apoptosis was explored through various methods, such as flow cytometry analysis, morphological changes, activation of caspase 3, ROS, and MMP. Our findings revealed that compound 5g induced apoptosis in the PC3 cell line, which was demonstrated by activation of caspase 3, an increase in ROS levels, and early apoptosis percentage. These results suggest that compound 5g holds promise as a potential therapeutic approach to cancer treatment.

Facile Functionalization of Ambipolar, Nitrogen-Doped PAHs toward Highly Efficient TADF OLED Emitters.

Despite promising optoelectronic features of N-doped polycyclic aromatic hydrocarbons (PAHs), their use as functional materials remains underdeveloped due to their limited post-functionalization. Facing this challenge, a novel design of N-doped PAHs with D-A-D electronic structure for thermally activated delayed fluorescence (TADF) emitters was performed. Implementing a set of auxiliary donors at the meta position of the protruding phenyl ring of quinoxaline triggers an increase in the charge-transfer property simultaneously decreasing the delayed fluorescence lifetime. This, in turn, contributes to a narrow (0.04-0.28 eV) singlet-triplet exchange energy split (ΔEST) and promotes a reverse intersystem crossing transition that is pivotal for an efficient TADF process. Boosting the electron-donating ability of our N-PAH scaffold leads to excellent photoluminescence quantum yield that was found in a solid-state matrix up to 96% (for phenoxazine-substituted derivatives, under air) with yellow or orange-red emission, depending on the specific compound. Organic light-emitting diodes (OLEDs) utilizing six, (D-A)-D, N-PAH emitters demonstrate a significant throughput with a maximum external quantum efficiency of 21.9% which is accompanied by remarkable luminance values which were found for all investigated devices in the range of 20,000-30,100 cd/m2 which is the highest reported to date for N-doped PAHs investigated in the OLED domain.

Synthesis and structure determination of a synthetic cannabinoid CUMYL-THPINACA metabolite with differentiation between the ortho-, meta-, and para-hydroxyl positions of the cumyl moiety.

Synthetic cannabinoids, a type of new psychoactive substances, are likely to be rapidly metabolized; thus, the detection of their metabolites, rather than the parent compound, is a common method used to prove drug consumption. Although the analysis of metabolites is generally performed by mass spectrometry, it is limited to structural estimation because of few commercially available standards. In particular, distinguishing between positional isomers is difficult. Synthetic cannabinoids with a cumyl moiety can be hydroxylated at the cumyl moiety during metabolism, but it remains unclear whether the hydroxylation occurs at the ortho, meta, or para position. This study determined the structures of a metabolite formed by mono-hydroxylation at the cumyl moiety of the synthetic cannabinoid CUMYL-THPINACA, used as a model compound. Chemical synthesis was performed to create possible metabolites with one hydroxyl group at the ortho, meta, or para positions of the cumyl moiety. Using the synthesized metabolites and liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolite detected in the microsomal reaction of CUMYL-THPINACA was identified as a compound mono-hydroxylated at the para position based on retention time and product ion spectra. Moreover, the rapid metabolism of CUMYL-THPINACA was demonstrated with an in vitro half-life of 4.9 min and the identified metabolite could be detected for a relatively long time in vitro. The synthesized metabolite may be utilized as a good reference standard for proof of CUMYL-THPINACA consumption. These findings have potential applications in the synthesis of metabolites of other synthetic cannabinoids bearing a cumyl moiety.

Characterization of thermodynamic properties on Al3+/dopamine system

The interactions of dopamine (Dop−) with aluminum were studied in NaCl(aq) at different ionic strengths (0.15 ≤ I/mol dm−3 ≤ 1.0) and temperatures (288.15 ≤ T/K ≤ 310.15). The investigations were carried out by using ISE-[H+] potentiometry, UV–Vis spectrophotometry and 1H NMR. The results obtained from the different techniques were in good agreement, both in terms of speciation model and stability constants of the complexes. The speciation model is featured by mononuclear complexes, namely: AlDop; AlDopOH; AlDop(OH)2 and AlDop(OH)3 (charges omitted). From 1H NMR investigations, it resulted that both the amino and the phenolic groups in meta position of aromatic ring are involved in the protonation equilibria, while the Al3+ complexation occurs from the catechol side of the ligand. The dependence on the ionic strength and temperature of the complex formation constants was modelled by a modified extended Debye-Hückel equation, containing a term for the dependence on T/K. The SIT approach allowed the calculation of the specific ion interaction coefficients of the aluminum:dopamine complexes. From the enthalpy change values obtained, it resulted that the formation of the species is exothermic in nature and that the entropy is the driving force of the processes. The sequestering ability of dopamine towards Al3+ was evaluated by the calculation of pL0.5 parameter at different ionic strengths, pHs and temperatures; the dependence of the pL0.5 on these variables was modelled by using an empirical predictive equation that allows the calculation of the effective sequestering ability of dopamine at desired conditions. The precipitates collected at the end of the potentiometric titrations were studied by means of thermogravimetric (TGA) analysis.

Halogen Bonding Interactions of Haloaromatic Endocrine Disruptors and the Potential for Inhibition of Iodothyronine Deiodinases

AbstractHalogen bonding (XB) is a potential mechanism for the inhibition of the thyroid‐activating/deactivating iodothyronine deiodinase family of selenoproteins through interactions with halogenated endocrine disrupting compounds (EDCs). Trends in XB interactions were examined using density functional theory for a series of polyhalogenated dibenzo‐1,4‐dioxins, biphenyls, and other EDCs with methylselenolate, a simple model of the Dio active site selenocysteine. The strengths of the interactions depend upon the halogen (Br>Cl), the degree of substitution, and the position of the acceptor. In terms of donor‐acceptor energies, interactions at the meta position are often the strongest, suggesting a link to the topology of THs, especially for outer‐ring deiodination of thyroxine, which occurs at a meta iodine, and produces the active TH. However, relationships between XB interaction strengths and potential for Dio inhibition should be made in the context of the binding to the active sites, the topology of which are not fully characterized.

6-Bromoquinazoline Derivatives as Potent Anticancer Agents: Synthesis, Cytotoxic Evaluation, and Computational Studies.

A series of 6-bromoquinazoline derivatives (5a-j) were synthesized. Cytotoxic effectiveness of compounds was done against two cancerous cell lines (MCF-7 and SW480) by standard MTT method. Fortunately, all of the compounds showed desirable activity in reducing the viability of the studied cancerous cell lines with IC50 value in the range of 0.53-46.6 μM. Compound 5b with a fluoro substitution at meta position of the phenyl moiety showed stronger activity than cisplatin with IC50 =0.53-1.95 μM. Studies on the hit compound (5b) through apoptosis assay illustrated that it could induce apoptosis in MCF-7 cell lines in dose dependent manner. Molecular docking study was done to investigate the detailed binding modes and interactions with EGFR as a plausible mechanism. The drug- likeness was predicted. To survey the reactivity of compounds, DFT calculation was performed. Taken together, 6-bromoquinazoline derivatives, especially 5b can be considered as hit compounds to rational drug designing as antiproliferative agents.

Antileishmanial activity of tetra-cationic porphyrins with peripheral Pt(II) and Pd(II) complexes mediated by photodynamic therapy

Leishmaniasis is a neglected disease that impacts more than one billion people in endemic areas of the globe. Several drawbacks are associated with the currently existing drugs for treatment such as low effectiveness, toxicity, and the emergence of resistant strains that demonstrate the importance of looking for novel therapeutic alternatives. Photodynamic therapy (PDT) is a promising novel alternative for cutaneous leishmaniasis treatment because its topical application avoids potential side effects generally associated with oral/parenteral application. A light-sensitive compound known as photosensitizer (PS) interacts with light and molecular oxygen to generate reactive oxygen species (ROS), which promote cell death by oxidative stress through PDT approaches. Here, for the first time, we demonstrate the antileishmanial effect of tetra-cationic porphyrins with peripheral Pt(II)- and Pd(II)-polypyridyl complexes using PDT. The isomeric tetra-cationic porphyrins in the meta positions, 3-PtTPyP, and 3-PdTPyP, exhibited the highest antiparasitic activity against promastigote (IC50-pro = 41.8 nM and 46.1 nM, respectively) and intracellular amastigote forms (IC50-ama = 27.6 nM and 38.8 nM, respectively) of L. amazonensis under white light irradiation (72 J cm–2) with high selectivity (SI > 50) for both forms of parasites regarding mammalian cells. In addition, these PS induced the cell death of parasites principally by a necrotic process in the presence of white light by mitochondrial and acidic compartments accumulation. This study showed that porphyrins 3-PtTPyP and 3-PdTPyP displayed a promising antileishmanial-PDT activity with potential application for cutaneous leishmaniasis treatment.

Proton tautomerism in 5-dimethylaminomethylidene-4-(o-,m-,p-hydroxyphenyl)amino-1,3-thiazol-2(5H)-ones: synthesis, crystal structure and spectroscopic studies.

Three new 5-dimethylaminomethylidene-4-phenylamino-1,3-thiazol-2(5H)-ones with an hydroxyl group in the ortho-, meta- and para- positions on the phenyl ring were synthesized in order to deduce the structural changes occurring on prototropic tautomerism of the amidine system. The existence of all the title compounds solely in the amino tautomeric form has been established in the solid and liquid (dimethyl sulfoxide solution) phases. The title compounds are analyzed from the point of view of the electronic effects and conformational freedom of their molecules. The intermolecular interactions in the crystals and their supramolecular architecture are highlighted.

Leveraging a Structural Blueprint to Rationally Engineer the Rieske Oxygenase TsaM.

Rieske nonheme iron oxygenases use two metallocenters, a Rieske-type [2Fe-2S] cluster and a mononuclear iron center, to catalyze oxidation reactions on a broad range of substrates. These enzymes are widely used by microorganisms to degrade environmental pollutants and to build complexity in a myriad of biosynthetic pathways that are industrially interesting. However, despite the value of this chemistry, there is a dearth of understanding regarding the structure-function relationships in this enzyme class, which limits our ability to rationally redesign, optimize, and ultimately exploit the chemistry of these enzymes. Therefore, in this work, by leveraging a combination of available structural information and state-of-the-art protein modeling tools, we show that three "hotspot" regions can be targeted to alter the site selectivity, substrate preference, and substrate scope of the Rieske oxygenase p-toluenesulfonate methyl monooxygenase (TsaM). Through mutation of six to 10 residues distributed between three protein regions, TsaM was engineered to behave as either vanillate monooxygenase (VanA) or dicamba monooxygenase (DdmC). This engineering feat means that TsaM was rationally engineered to catalyze an oxidation reaction at the meta and ortho positions of an aromatic substrate, rather than its favored native para position, and that TsaM was redesigned to perform chemistry on dicamba, a substrate that is not natively accepted by the enzyme. This work thus contributes to unlocking our understanding of structure-function relationships in the Rieske oxygenase enzyme class and expands foundational principles for future engineering of these metalloenzymes.

Water-Soluble Gd(III)-Porphyrin Complexes Capable of Both Photosensitization and Relaxation Enhancement.

With the aim of developing more stable Gd(III)-porphyrin complexes, two types of ligands 1 and 2 with carboxylic acid anchors were synthesized. Due to the N-substituted pyridyl cation attached to the porphyrin core, these porphyrin ligands were highly water-soluble and formed the corresponding Gd(III) chelates, Gd-1 and Gd-2. Gd-1 was sufficiently stable in neutral buffer, presumably due to the preferred conformation of the carboxylate-terminated anchors connected to nitrogen in the meta position of the pyridyl group helping to stabilize Gd(III) complexation by the porphyrin center. 1H NMRD (nuclear magnetic relaxation dispersion) measurements on Gd-1 revealed high longitudinal water proton relaxivity (r1 = 21.2 mM-1 s-1 at 60 MHz and 25 °C), which originates from slow rotational motion resulting from aggregation in aqueous solution. Under visible light irradiation, Gd-1 showed extensive photoinduced DNA cleavage in line with efficient photoinduced singlet oxygen generation. Cell-based assays revealed no significant dark cytotoxicity of Gd-1, while it showed sufficient photocytotoxicity on cancer cell lines under visible light irradiation. These results indicate the potential of this Gd(III)-porphyrin complex (Gd-1) as a core for the development of bifunctional systems acting as an efficient photodynamic therapy photosensitizer (PDT-PS) with magnetic resonance imaging (MRI) detection capabilities.

Dipeptide Nitrile CD34 with Curcumin: A New Improved Combination Strategy to Synergistically Inhibit Rhodesain of Trypanosoma brucei rhodesiense.

Rhodesain is the main cysteine protease of Trypanosoma brucei rhodesiense, the parasite causing the acute lethal form of Human African Trypanosomiasis. Starting from the dipeptide nitrile CD24, the further introduction of a fluorine atom in the meta position of the phenyl ring spanning in the P3 site and the switch of the P2 leucine with a phenylalanine led to CD34, a synthetic inhibitor that shows a nanomolar binding affinity towards rhodesain (Ki = 27 nM) and an improved target selectivity with respect to the parent dipeptide nitrile CD24. In the present work, following the Chou and Talalay method, we carried out a combination study of CD34 with curcumin, a nutraceutical obtained from Curcuma longa L. Starting from an affected fraction (fa) of rhodesain inhibition of 0.5 (i.e., the IC50), we observed an initial moderate synergistic action, which became a synergism for fa values ranging from 0.6 to 0.7 (i.e., 60-70% inhibition of the trypanosomal protease). Interestingly, at 80-90% inhibition of rhodesain proteolytic activity, we observed a strong synergism, resulting in 100% enzyme inhibition. Overall, in addition to the improved target selectivity of CD34 with respect to CD24, the combination of CD34 + curcumin resulted in an increased synergistic action with respect to CD24 + curcumin, thus suggesting that it is desirable to use CD34 and curcumin in combination.

Direct Arylation of C(sp2)–H Bonds in Anilines

AbstractAnilines selectively arylated at their ortho, meta or para positions are useful building blocks in synthesis and have found applications in many areas. The most straightforward method for their synthesis relies on the direct arylation of a C(sp2)–H bond of anilines, an attractive strategy avoiding the prefunctionalization of the starting anilines provided that such arylations proceed with high levels of regioselectivity. Such reactions are presented and discussed, in a comprehensive manner, in this review article, with an emphasis on the regioselectivity of the processes and factors governing both the reactivity and selectivity. 1 Introduction2 ortho-Arylation of Anilines2.1 Direct C(sp2)–H ortho-Arylation of Anilines2.2 Directed C(sp2)–H ortho-Arylation of Anilines3 meta-Arylation of Anilines4 para-Arylation of Anilines4.1 Direct C(sp2)–H para-Arylation of Anilines via Oxidative Radical Homodimerization4.2 Direct C(sp2)–H para-Arylation of Anilines via Transition-Metal Catalysis5 Conclusion and Outlook

Discovery of urea-based pleuromutilin derivatives as potent gram-positive antibacterial agents

There is an urgent need to discover new antibacterial drugs and provide new treatment options for clinical antimicrobial resistance (AMR) pathogen infections. Inspired by the structural insights from analyzing the co-crystal structure of lefamulin with the ribosomes of S. aureus, a series of novel pleuromutilin derivatives of phenylene sulfide incorporated with urea moiety were designed and synthesized. The structure–activity relationship (SAR) study revealed that derivatives with urea in the meta position of phenylene sulfide had optimal antibacterial activities in vitro. Among them, 21h was the most potent one against Methicillin-resistant Staphylococcus aureus (MRSA) and clinical AMR Gram-positive bacteria with minimum inhibitory concentrations (MICs) in the range of 0.00195–0.250 μg/mL. And it possessed low resistance frequency, prolonged Post-Antibiotic Effect and the capability to overcome lefamulin-induced resistance. Furthermore, 21h exhibited potent antibacterial activity in vivo in both the thigh infection model and trauma infection model, representing a promising lead for the development of new antibiotics against Gram-positive pathogens, especially for AMR bacteria.

Physicochemical properties, drug likeness, ADMET, DFT studies, and in vitro antioxidant activity of oxindole derivatives

Poor pharmacokinetic and safety profiles create significant hurdles in the drug development process. This work focuses on a detailed understanding of drug discovery interplay among physicochemical, pharmacokinetic, toxicity endpoints, and antioxidant properties of oxindole derivatives. DFT compıutations were also performed at B3LYP/6-311G** level to evaluate the physicochemical properties, global reactivity features, and intramolecular interactions. The BOILED-Egg pharmacokinetic model envisaged gastrointestinal absorption, blood-brain barrier penetration, and no interaction with p-glycoprotein for compounds C1 and C2. The physicochemical evaluation revealed that C1 possesses superior drug-like properties fit for oral absorption. Both derivatives were predicted to have high plasma protein binding, efficient distribution, and inhibiting CYP 450 major isoforms but serve as substrates only for a few of them. Both molecules have mild to moderate clearance rates. Out of ten toxicity parameters, only hepatotoxicity was predicted. DFT results implied that the meta position of the -OH group made the possibility of charge transfer greater than -para positioned -OH, due to the ΔNmax (eV) values of molecules C1 and C2 being calculated at 2.596 and 2.477, respectively. Both C1 and C2 exhibited a concentration dependant DPPH and ABTS radical scavenging activity. The chemical structure-physicochemical-pharmacokinetic relationship identified the meta position as the favorite for the electron-withdrawing hydroxyl group. This provides useful insight to medicinal chemists to design 6-chlorooxindole derivatives with an acceptable drug-like and pharmacokinetic property.

Bioaccumulation, Trophic Transfer, and Biotransformation of Polychlorinated Diphenyl Ethers in a Simulated Aquatic Food Chain.

Polychlorinated diphenyl ethers (PCDEs) are detected in aquatic environments and demonstrate adverse effects in aquatic organisms. However, data regarding the environmental behavior of PCDEs in aquatic ecosystems are lacking. In the present study, a simulated aquatic food chain (Scenedesmus obliquus-Daphnia magna-Danio rerio) was constructed in a lab setting, and the bioaccumulation, trophic transfer, and biotransformation of 12 PCDE congeners were quantitatively investigated for the first time. The log-transformed bioaccumulation factors (BCFs) of PCDEs in S. obliquus, D. magna, and D. rerio were in the range of 2.94-3.77, 3.29-4.03, and 2.42-2.89 L/kg w.w., respectively, indicating the species-specific bioaccumulation of PCDE congeners. The BCF values increased significantly with the increasing number of substituted Cl atoms, with the exception of CDE 209. The number of Cl atoms at the para and meta positions were found to be the major positive contributing factors for BCFs in the case of the same number of substituted Cl. The lipid-normalized biomagnification factors (BMFs) of S. obliquus to D. magna, D. magna to D. rerio, and the whole food chain for the 12 PCDE congeners ranged at 1.08-2.27, 0.81-1.64, and 0.88-3.64, respectively, suggesting that some congeners had BMFs comparable to PBDEs and PCBs. Dechlorination was the only metabolic pathway observed for S. obliquus and D. magna. For D. rerio, dechlorination, methoxylation, and hydroxylation metabolic pathways were observed. 1H nuclear magnetic resonance (NMR) experiments and theoretical calculations confirmed that methoxylation and hydroxylation occurred at the ortho position of the benzene rings. In addition, reliable quantitative structure-property relationship (QSPR) models were constructed to qualitatively describe the relationships between molecular structure descriptors and BCFs for PCDEs. These findings provide insights into the movement and transformation of PCDEs in aquatic ecosystems.

Rational Design and Lead Optimisation of Potent Antimalarial Quinazolinediones and Their Cytotoxicity against MCF-7.

Quinazolinedione is one of the most outstanding heterocycles in medicinal chemistry thanks to its wide ranges of biological activities including antimalarial, anticancer, and anti-inflammatory. TCMDC-125133 containing a quinazolinedione pharmacophore displays promising antimalarial activity and low toxicity, as described in the GlaxoSmithKline (GSK) report. Herein, the design and synthesis of novel quinazolinedione derivatives is described on the basis of our previous work on the synthesis of TCMDC-125133, where low-cost chemicals and greener alternatives were used when possible. The initial SAR study focused on the replacement of the valine linker moiety; according to the in silico prediction using SwissADME, concise four-step syntheses toward compounds 4-10 were developed. The in-house synthesized compounds 4-10 were assayed for antimalarial activity against P. falciparum 3D7, and the result revealed that only the compound 2 containing a valine linker was tolerated. Another round of lead optimization focused on the replacement of the m-anisidine moiety in compound 2. A library of 12 derivatives was prepared, and the antimalarial assay showed that potent antimalarial activity could be maintained by replacing the methoxy group in the meta position of the phenyl side chain with a fluorine or chlorine atom (21: IC50 = 36 ± 5 nM, 24: IC50 = 22 ± 5 nM). Further lead optimization is underway to enhance the antimalarial activity of this class of compound. The compounds included in the study possess little to no antiproliferative activity against MCF-7 cells.

Palladium-Catalyzed [3 + 2] Annulation of Aromatic Amides with Maleimides through Dual C-H Activation.

A palladium-catalyzed [3 + 2] annulation of substituted aromatic amides with maleimides providing tricyclic heterocyclic molecules in good to moderate yields through weak carbonyl chelation is reported. The reaction proceeds via a dual C-H bond activation where the first C-H activation takes place selectively at the benzylic position followed by a second C-H bond activation at the meta position to afford a five-membered cyclic ring. An external ligand Ac-Gly-OH has been used to succeed in this protocol. A plausible reaction mechanism has been proposed for the [3 + 2] annulation reaction.

Structural and Magnetic Investigation of Cobalt Valence Tautomeric Complexes with Sulfur-Containing Ligands

We report a series of heteroleptic cobalt complexes of the general formula [Co(tBu2sq)2(L)2], where tBu2sq = 3,5-di(tert-butyl)-o-semiquinonato ligand and L represents pyridines functionalized with sulfur-containing substituents. The octahedral coordination of the Co metal center in these mononuclear complexes is formed by two chelating tBu2sq ligands in the equatorial plane and two axial pyridines in the axial positions. All complexes exhibit layered crystal packings, with S-containing substituents providing cohesion within the layers and the tBu substituents of dioxolenes protruding into the interlayer space, where disordered solvent molecules are located. The presence of thienyl substituents in the para position of the pyridine ring leads to the formation of molecular chains within the layers, due to efficient π–π interactions between the L ligands. Even more efficient packing with two-dimensional intermolecular π–π interactions is achieved when two thienyl substituents are present in the meta positions of the pyridine ring. Introduction of a terminal cyano or 1,3-dithiole-2-one substituent on the opposite end of the pyridyl-bound thienyl group leads to the disruption of the π–π interactions, thus decreasing the crystal packing efficiency. Such disruption, however, is not observed when the thienyl group is terminated with methyl-carboxylate. Magnetic measurements reveal an onset of valence-tautomeric spin-crossover (VT-SCO) from the [LS-CoIII(tBu2sq•)(tBu2cat)(L)2] state (low-spin, S = 1/2) to the [HS-CoII(tBu2sq•)2(L)2] state (high-spin, S = 5/2) above 300 K for the complexes with para-thienyl-substituted pyridines, while the complexes with a bithienyl substituent in the para position or two thienyl substituents in the meta positions exhibit only LS state up to 400 K. Adding a terminal group to the para-thienyl substituent lowers the VT-SCO temperature, leading to two-step spin-state conversion.

Divergent Synthesis of Helical Ketone Enabled by Rearrangement of Spiro Carbocation.

An acid-mediated electrophilic cyclization of 2-alkynyl-1,1'-biphenyls for the divergent synthesis of angular, bent, and zigzag fused nonplanar conjugated organic molecules was realized. The key feature of this reaction is a Wagner-Meerwein-type rearrangement via a spiro carbocation intermediate, which was formed by electrophilic cyclization of the 9H-fluoren-9-one derivative at the meta position. The products can be advanced to helical fluorenes, which exhibit high fluorescence quantum yields.

Substituent Effects in Tetrel Bonds Involving Aromatic Silane Derivatives: An ab initio Study.

In this manuscript substituent effects in several silicon tetrel bonding (TtB) complexes were investigated at the RI-MP2/def2-TZVP level of theory. Particularly, we have analysed how the interaction energy is influenced by the electronic nature of the substituent in both donor and acceptor moieties. To achieve that, several tetrafluorophenyl silane derivatives have been substituted at the meta and para positions by several electron donating and electron withdrawing groups (EDG and EWG, respectively), such as -NH2, -OCH3, -CH3, -H, -CF3 and -CN substituents. As electron donor molecules, we have used a series of hydrogen cyanide derivatives using the same EDGs and EWGs. We have obtained the Hammett's plots for different combinations of donors and acceptors and in all cases we have obtained good regression plots (interaction energies vs. Hammet's σ parameter). In addition, we have used the electrostatic potential (ESP) surface analysis as well as the Bader's theory of atoms in molecules (AIM) and noncovalent interaction plot (NCI plot) techniques to further characterize the TtBs studied herein. Finally, a Cambridge Structural Database (CSD) inspection was carried out, retrieving several structures where halogenated aromatic silanes participate in tetrel bonding interactions, being an additional stabilization force of their supramolecular architectures.