Covalent Interactions Research Articles

Harnessing Nanomaterials for Enhanced DNA-Based Biosensing and Therapeutic Performance.

The integration of nanomaterials with DNA-based systems has emerged as a transformative approach in biosensing and therapeutic applications. Unique features of DNA, like its programmability and specificity, complement the diverse functions of nanomaterials, leading to the creation of advanced systems for detecting biomarkers and delivering treatments. Here, we review the developments in DNA-nanomaterial conjugates, emphasizing their enhanced functionalities and potential across various biomedical applications. We first discuss the methodologies for synthesizing these conjugates, distinguishing between covalent and non-covalent interactions. We then categorize DNA-nanomaterials conjugates based on the properties of the DNA and nanomaterials involved, respectively. DNA probes are classified by their application into biosensing or therapeutic uses, and, several nanomaterials are highlighted by their recent progress in living biological. Finally, we discuss the current challenges and future prospects in this field, anticipating that significant progress in DNA-nanomaterial conjugates will greatly enhance precision medicine.

Structural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies.

Acquired immunodeficiency syndrome (AIDS) poses a significant threat to life. Antiretroviral therapy is employed to diminish the replication of the human immunodeficiency virus (HIV), extending life expectancy and improving the quality of patients' lives. These HIV-1 integrase inhibitors form robust covalent interactions with Mg2+ ions, contributing to their tight binding, thereby inhibiting the integration of viral DNA into the CD4 cell DNA. The second-generation INSTIs, the most recently approved, exhibit a higher genetic barrier compared to first-generation drugs. Hence, there is a need to develop novel and safe compounds as inhibitors of HIV-1 integrase. This article presents an overview of the current landscape of anti-HIV-1 integrase inhibitors, emphasizing the structure-activity relationship (SAR) of small molecules. The molecules discussed include monocyclic rings consisting of triazoles moiety, and pyrimidine analog along with bicyclic rings with nitrogen-containing moieties. Researchers are exploring anti-HIV-1 integrase inhibitors from natural sources like marine environments, plant extracts, and microbial products, emphasizing the importance of diverse bioactive compounds in combating the virus, which have also been included in the manuscript. The current manuscript will be helpful to the scientific community engaged in the manipulation of small molecules as anti-HIV integrase inhibitors for designing newer leads.

Nanoarchitectonics in immobilization of DNT/TNT specific binding peptides on laser-induced graphene

Abstract Bio/chemical sensors require high selectivity for specific targets. Carbon nanomaterials, especially graphene-based materials, are preferred in sensors due to their high surface area, superior electrical conductivity, mechanical strength, and flexibility. In this study, DNT-bp (Dinitrotoluene binding peptide) and TNT-bp (Trinitrotoluene binding peptide) were immobilized on LIG (Laser-induced graphene) films through covalent and non-covalent interactions. EDC (1-ethyl-3-3-dimethylaminopropyl carbodiimide hydrochloride) is used to activate carboxylic acid groups, which then react with NHS (N-hydroxysuccinimide) to form NHS esters, facilitating the binding of amine-containing peptides to the LIG surface. XPS analysis of LIG films functionalized with EDC+NHS shows a decrease in COOH (carboxyl) and an increase in C-N/C=N/C-O groups. N1s peak at high-resolution XPS spectrum indicates that DNT-bp immobilization leads to higher elimination of NHS-esters, resulting in fewer N-C=O (amide) functional groups and more protonated nitrogen, which suggests that DNT-bp immobilization is more effective than TNT-bp immobilization. The findings suggest that LIG-based sensors provide a cost-effective platform for the detection of DNT (2,4-dinitrotoluene) and 2,4,6-trinitrotoluene (TNT). Further advancements in LIG-based biosensors may enable their broader application in security, environmental monitoring, and health diagnostics.

An electrochemical biosensor for mercury(II) detection based on DNA-Au bio-bar codes coupled with enzymatic dual signal amplification

Mercury ion (Hg2+) is one of the most toxic heavy metal pollutants, which not only causes enormous damage and pollution to environment, but also results in numerous irreversible impairments to the human health. Herein, a novel amperometric DNA biosensor was constructed for Hg2+ detection based on DNA-Au bio-bar codes coupled with enzymatic dual signal amplification. Carboxylated graphene oxide (GO − COOH) was selected as electrode modified material to provide anchoring sites for attachment DNA oligonucleotides. Substrate DNA was attached on the GO − COOH surface via covalent coupling interaction between amine (–NH2) groups on DNA and carboxyl (–COOH) groups on GO. AuNPs co-linked with bio-bar code DNA and target DNA via Au-S bonds were utilized as DNA-Au bio-bar codes, which labeled with HRP through avidin/biotin interaction. In the presence of object Hg2+, the target DNA on HRP-labeled DNA-Au bio-bar codes (HRP-DNA-Au bio-bar codes) hybridized with substrate DNA on GO − COOH via thymine-Hg2+-thymine (T-Hg2+-T) coordination chemistry. HRP-DNA-Au bio-bar codes catalyze hydroquinone oxidation to benzoquinone in presence of by hydrogen peroxide, generating an enhanced amperometric response signal. The current signal of biosensor is proportional to the logarithm of Hg2+ concentrations ranging from 25 pM to 10 μM with a detection limit of 10 pM (S/N = 3). Furthermore, without the need for target amplification, the prepared electrochemical DNA biosensor exhibited superior selectivity against other interfering metal ions, providing a facile and sensitive platform for Hg2+ detection in real environmental samples.

Interaction-Based Inductive Bias in Graph Neural Networks: Enhancing Protein-Ligand Binding Affinity Predictions From 3D Structures.

Inductive bias in machine learning (ML) is the set of assumptions describing how a model makes predictions. Different ML-based methods for protein-ligand binding affinity (PLA) prediction have different inductive biases, leading to different levels of generalization capability and interpretability. Intuitively, the inductive bias of an ML-based model for PLA prediction should fit in with biological mechanisms relevant for binding to achieve good predictions with meaningful reasons. To this end, we propose an interaction-based inductive bias to restrict neural networks to functions relevant for binding with two assumptions: 1) A protein-ligand complex can be naturally expressed as a heterogeneous graph with covalent and non-covalent interactions; 2) The predicted PLA is the sum of pairwise atom-atom affinities determined by non-covalent interactions. The interaction-based inductive bias is embodied by an explainable heterogeneous interaction graph neural network (EHIGN) for explicitly modeling pairwise atom-atom interactions to predict PLA from 3D structures. Extensive experiments demonstrate that EHIGN achieves better generalization capability than other state-of-the-art ML-based baselines in PLA prediction and structure-based virtual screening. More importantly, comprehensive analyses of distance-affinity, pose-affinity, and substructure-affinity relations suggest that the interaction-based inductive bias can guide the model to learn atomic interactions that are consistent with physical reality. As a case study to demonstrate practical usefulness, our method is tested for predicting the efficacy of Nirmatrelvir against SARS-CoV-2 variants. EHIGN successfully recognizes the changes in the efficacy of Nirmatrelvir for different SARS-CoV-2 variants with meaningful reasons.

Interlayer toughening effect of graphene oxide and polydopamine modified kevlar fiber on the carbon fiber panel/plastic honeycomb sandwich structure

This study examines the performance of modified Kevlar fiber-reinforced carbon fiber/plastic honeycomb panels. Graphene oxide (GO) is successfully grafted onto the Kevlar fiber surface using polydopamine (PDA) as a binding medium. The combined effect of GO and PDA's secondary functionalization significantly improves bonding strength. The toughened samples exhibit markedly higher peak force and energy absorption compared to the untoughened ones. Specifically, the PDA-GO-2 toughened specimen shows the best performance, with peak force and energy absorption increased by 70.9% and 109.4%, respectively. Kevlar fibers and resin form a complex "compound and rounded structure" at the edge of the honeycomb core. This structure enhances the bonding strength between the carbon fiber-reinforced polymer (CFRP) panel and the polypropylene (PP) honeycomb core. Furthermore, the PDA and GO treatment improves the fibers' wettability, tensile strength, surface roughness, and specific surface area, facilitating better mechanical interlocking between the fiber and resin. GO enhances the contact between epoxy resin and fibers by facilitating covalent and hydrogen bond interactions, resulting in a tighter transition interface that improves the interfacial adhesion strength between the fibers and the resin.

On the potential of Zn@B38 superatom as a drug delivery vehicle for several anticancer drugs: A DFT study

The interaction between a boron-based Zn@B38 superatom and five drugs, including cisplatin (DDP), 5-fluorouracil (FU), mercaptopurine (MP), hydroxyurea (HU) and nitrogen mustard (CM) have been investigated. The adsorption of these anticancer drugs onto Zn@B38 reduces the energy gap of this superatom. Except for DDP, these drugs exhibit strong covalent interaction with the vertex of Zn@B38 because the lone pair of N/O atom of FU, MP, HU, and CM can fill into the empty atomic orbital of the electron-deficient boron atom of Zn@B38 to form polar covalent bonds, resulting in the charge transfer from drugs to Zn@B38. Hence, the adsorption energies of drug@[Zn@B38] (drug = FU, MP, HU, and CM) are −37.67 ∼ −57.21 kcal/mol, but can be significantly decreased to −8.63 ∼ 5.48 kcal/mol upon protonation, suggesting that these drugs can be efficiently adsorbed by the Zn@B38 carrier in neutral aqueous solution but are easily released in the acidic tumor microenvironment.

Formation of complex organics by covalent and non-covalent interactions of the sequential reactions of 1-4 acrylonitrile molecules with the benzonitrile radical cation.

Benzonitrile molecules are present in ionizing environments including interstellar clouds and solar nebulae, where their ions can form adducts with neutral molecules such as acrylonitrile leading to the formation of a variety of nitrogen-containing complex organics. Herein, we report on the formation of complex organics by the sequential reactions of 1-4 acrylonitrile (C3NH3) molecules with the benzonitrile radical cation (C7NH5+˙). The results reveal the formation of the covalently bonded N-acrylonitrile-benzonitrile radical cation (C10N2H8+˙) with a rate coefficient of 2.2 (±0.4) × 10-11 cm3 s-1 at 423 K and a calculated collision cross-section of 73.8 Å2 in good agreement with the measured cross-section of 70.7 Å2 of the C10N2H8+˙ adduct. Subsequent reversible association of 1-3 acrylonitrile molecules with the N-acrylonitrile-benzonitrile radical cation (C10N2H8+˙) at lower temperatures (250-200 K) results in the formation of the N-rich clusters (C10N2H8+˙)(C3NH3)1-3 which can be enhanced in the very cold cores of the interstellar medium (ISM) and could offer unique potential candidates for the substantial amount of nitrogen carriers detected in the emission spectra of the ISM. The observed N-acrylonitrile-benzonitrile covalent adduct and its associated acrylonitrile clusters could have significant implications in the formation of different types of complex organics in different regions of outer space. It is anticipated that the current results would have direct implications in the search for nitrogen-containing complex organics in space.

Revealing the Critical Role of the Lone Pair Electrons of Bi3+ in Electrocatalytic Oxygen Reduction Reaction on Mn‐Based BiMn2O5 Mullite Surface

AbstractThere is a research gap regarding the role of lone pair electrons of post‐transition metal cations in catalysis field, yet such studies hold significant implications for expanding their applications. Herein, the role of Bi3+ ion lone pair electrons in electrocatalytic oxygen reduction reaction (ORR) is elucidated using ternary mullite oxides as prototype catalysts. Among the three synthesized mullites ((Sm/Y/Bi)Mn2O5), BiMn2O5 exhibits notably superior ORR catalytic activity. Through advanced characterization techniques, including in situ Raman, in situ infrared, and X‐ray absorption spectroscopy, combined with theoretical calculations, it is determined that the superior electrocatalytic performance of BiMn2O5 originates from the lone pair electrons that activate catalytic sites through stereochemical effects. Specifically, the Bi3+ lone pair electrons in the 6s orbital near Fermi level interact with O 2p orbitals, causing a shift of the oxygen ligands, and significant variance in A─O bond lengths. This structural distortion of BiO8 coordination unit directly results in a large Mn─O bond angle at the active center of BiMn2O5 and strong covalent interactions, facilitating charge transfer and refining the adsorption behavior of oxygen intermediates to achieve the overpotential of 0.25 V vs. RHE. This study provides insights into developing next‐generation catalysts by harnessing the lone pair electrons of post‐transition metal cations.

The application of monoglycerides to improve the quality of fresh noodles: Discerning the roles of acyl chain length and dispersity

Monoglycerides are widely used in flour-based products, but the roles of their dispersibility and acyl chain length remain unclear. This study investigated the effects of monoglycerides with different chain lengths (C12, C16, C18) dispersed in deionized water (DW) or 95 % ethanol (EE) on fresh noodle quality. Ethanol (2 mL per 200 g flour) had no significant effect on noodle properties, but monoglycerides in EE significantly altered gluten structure through covalent and non-covalent interactions, forming a denser gluten network, as observed by CLSM. Starch-lipid complex formation was confirmed by FT-IR, Raman, and XRD, enhancing cooking and immersion performance. Monoglycerides in EE were more effective than in DW, with impact orders: DW (C12 > C16 ≈ C18) and EE (C12 < C16 < C18), indicating solvent selection was more critical than chain length. This study refined the application method of monoglycerides, enhancing their functional performance and contributing to elevated noodle performance.

Managing Solvent Complexes to Amplify Ripening Process by Covalent Interaction Driving Force Under External Field for Perovskite Photovoltaic

AbstractUp to now, post‐annealing is most commonly used to post treat the perovskite film to accelerate the ripening process. Nonetheless, the top‐down crystallization mechanism impedes the efficient desolvation of solvent complexes. Thus, residual solvent complexes tend to accumulate at the bottom of the film during the ripening process and deteriorate the device. Here, a new strategy with unique concept is promoted to amplify ripening process of perovskite film, in which a nematic thermotropic liquid crystal (LC) molecular is introduced to facilitate the conversion of solvent complexes by utilizing the liquid crystalline behavior under external field. Upon the concurrent application of thermal and force fields, the covalent interaction between LC and solvent complexes generates a driving force, which promotes upward migration of solvent complexes, thereby facilitating their engagement in the ripening process. In addition, the driving force under external fields assists the flattening of grain boundary grooves. Therefore, film quality is improved efficiently with amplified ripening process and adequately handled buried interface. Based on the positive effects, the devices achieve a champion efficiency of 25.24%, and sustained ≈75% of its initial efficiency level even after undergoing a damp heat test (85 °C/85% RH) for 1400 h.

Length and Sequence-Selective Polymer Synthesis Templated by a Combination of Covalent and Noncovalent Base-Pairing Interactions.

Information can be encoded and stored in sequences of monomer units organized in linear synthetic polymers. Replication of sequence information is of fundamental importance in biology; however, it represents a challenge for synthetic polymer chemistry. A combination of covalent and noncovalent base pairs has been used to achieve high-fidelity templated synthesis of synthetic polymers that encode information as a sequence of different side-chain recognition units. Dialkyne building blocks were attached to the template by using ester base pairs, and diazide building blocks were attached to the template by using H-bond base pairs. Copper-catalyzed azide-alkyne cycloaddition reactions were used to zip up the copy strand on the template, and the resulting duplex was cleaved by hydrolyzing the covalent ester base pairs. By using recognition-encoded melamine oligomers with either three phosphine oxide or three 4-nitrophenol recognition units to form the noncovalent base pairs, exceptionally high affinities of the diazides for the template were achieved, allowing the templated polymerization step to be carried out at low concentrations, which promoted on-template intramolecular reactions relative to competing intermolecular processes. Two different templates, a 7-mer and an 11-mer, were used in the three-step reaction sequence to obtain the sequence-complementary copy strands with minimal amounts of side reaction.

Cation-lone pair interaction in Alkali/alkaline earth metal ion-heavier borazine analogue complexes.

The present study is the first report on the formation of alkali/alkaline earth metal ion-heavier borazine analogue complexes via cation-lone pair interaction. Density functional calculations are performed in scrutinizing the complex formation between alkali (Li+, Na+, K+)/alkaline earth (Be2+, Mg2+, Ca2+) metal ions and heavier borazine analogues (HBA) viz. B3P3H6, Al3N3H6, Al3P3H6, Al3As3H6, and Ga3P3-H6. The complexes are found to be stable in gas phase with stabilization energies within the range 26.40 to 324.74 kcalmol-1. The stability can be attributed to the polarizing power of the involved metal ions. Presence of solvent phase exerted notable impact on the stability of the complexes; stability is reduced significantly with the increase in solvent polarity. The process of complexation is exothermic and spontaneous. QTAIM analysis indicated the presence of both ionic and covalent interaction between HBAs and metal ions. HOMO energy, Wiberg bond index, NCI-isosurface and RDG plot analysis revealed the major role of cation-lone pair interaction in the complexation process.

Discovery of Chalcone Derivatives as Bifunctional Molecules with Anti-SARS-CoV-2 and Anti-inflammatory Activities.

Danshensu extracted with traditional Chinese medicine Salvia miltiorrhiza has a wide range of bioactivities. Danshensu containing a catechol moiety has a moderate inhibitory effect on SARS-CoV-2 3CLpro (IC50 = 2.2 μM) by a reversible covalent interaction and exhibits good anti-inflammatory activity. To enhance the inhibitory activity, we introduced Michael receptors into the side chain of danshensu as a possible covalent warhead and blocked the covalent binding sites of catechol moiety to yield chalcone derivatives. The resulting chalcone derivatives, A4 and A7, were found to inhibit SARS-CoV-2 3CLpro in vitro with IC50 values of 83.2 and 261.3 nM, respectively. Furthermore, A4 and A7 inhibit viral replication in the SARS-CoV-2 replicon system with EC50 values of 19.9 and 11.7 μM, respectively. Time-dependent inhibition experiment and mass spectrometry show that A4 acted as a noncovalent mixed inhibitor, while A7 likely binds covalently at Cys145. The interaction mechanism between SARS-CoV-2 3CLpro and A4 or A7 was characterized by molecular docking studies. Additionally, both A4 and A7 demonstrated potent anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. These promising results suggest that chalcone derivatives A4 and A7 can serve as bifunctional molecules with both antivirus and anti-inflammatory properties.

A Dynamical Density Field That Shows the Localizability of Electrons: The Exchange-Correlation Ehrenfest Force.

A gradual but steady tide in theoretical chemistry is favoring the exploration of atomic and molecular interactions through the dynamical forces perceived and exerted by the particles of a system. By integrating the quantum mechanical force operator over all the spin and all but one of the spatial coordinates of the electrons, the Ehrenfest force density field reveals these forces directly and is separable into a classical term, related to the electric field, and a quantum mechanical correction, which we introduce and analyze for various atoms and molecules in this work. This exchange-correlation Ehrenfest force density field, Fxc(r), excludes the dominant nuclear components that shape the full Ehrenfest field, revealing information about electron sharing, pairing, and delocalization. In a manner similar, though not equal, to the electron localization function, Fxc(r) unveils covalent and core basins. Its divergence, ∇·Fxc(r), indicates the presence of electron shells in atoms and recovers the positions of lone pairs and the shell structure of ionic, polar, and covalent interactions in molecules. It also exhibits a semiquantitative match with the Laplacian of the electron density that we also explore. In alignment with the established role of exchange-correlation as nature's glue, we demonstrate that a significant number of fundamental concepts in chemical bonding can be derived from the Fxc(r) dynamical field.

Cross-Linkable Fullerene Electron Transport Layer with Internal Encapsulation Capability for Efficient and Stable Inverted Perovskite Solar Cells.

A stable and compact fullerene electron transport layer (ETL) is crucial for high-performance inverted perovskite solar cells (PSCs). However, traditional fullerene-based ETLs like C60 and PCBM are prone to aggregate under operational conditions, a challenge recently recognized by academic and industrial researchers. Here, we designed and synthesized a novel cross-linkable fullerene molecule, bis((3-methyloxetan-3-yl)methyl) malonate-C60 monoadduct (BCM), for use as an ETL in PSCs. Upon a low-temperature annealing at 100 °C, BCM undergoes in-situ cross-linking to form a robust cross-linked BCM (CBCM) film, which demonstrates excellent electron mobility and a suitable band structure for efficient PSCs. Our results show that PSCs incorporating CBCM-based ETL achieve an impressive efficiency of 25.89% (certified: 25.36%), significantly surpassing the 23.25% efficiency of PCBM-based devices. The intramolecular covalent interactions within CBCM films effectively prevent aggregation and enhance film compactness, creating an internal encapsulation layer that mitigates the decomposition and ion migration of perovskite components. Consequently, CBCM-based PSCs show exceptional stability, maintaining 97.8% of their initial efficiency after 1000 hours of maximum power point tracking, compared to only 78.6% retention in PCBM-based devices after less than 820 hours.

Cross‐Linkable Fullerene Electron Transport Layer with Internal Encapsulation Capability for Efficient and Stable Inverted Perovskite Solar Cells

AbstractA stable and compact fullerene electron transport layer (ETL) is crucial for high‐performance inverted perovskite solar cells (PSCs). However, traditional fullerene‐based ETLs like C60 and PCBM are prone to aggregate under operational conditions, a challenge recently recognized by academic and industrial researchers. Here, we designed and synthesized a novel cross‐linkable fullerene molecule, bis((3‐methyloxetan‐3‐yl)methyl) malonate‐C60 monoadduct (BCM), for use as an ETL in PSCs. Upon a low‐temperature annealing at 100 °C, BCM undergoes in situ cross‐linking to form a robust cross‐linked BCM (CBCM) film, which demonstrates excellent electron mobility and a suitable band structure for efficient PSCs. Our results show that PSCs incorporating CBCM‐based ETL achieve an impressive efficiency of 25.89 % (certified: 25.36 %), significantly surpassing the 23.25 % efficiency of PCBM‐based devices. The intramolecular covalent interactions within CBCM films effectively prevent aggregation and enhance film compactness, creating an internal encapsulation layer that mitigates the decomposition and ion migration of perovskite components. Consequently, CBCM‐based PSCs show exceptional stability, maintaining 97.8 % of their initial efficiency after 1000 hours of maximum power point tracking, compared to only 78.6 % retention in PCBM‐based devices after less than 820 hours.

The non-covalent interaction between C3N and H2

Non-covalent interactions play an important role in numerous fields, particularly in physical hydrogen storage. The hydrogen storage properties of C3N are investigated by DFT calculations. The results indicated that H2 and C3N form physical adsorption. The electronic structure analysis demonstrates that both the covalent and electrostatic interactions between H2 and C3N are rather weak, while IRI analysis reveals that their interactions belong to non-valent interactions, and the further energy decomposition based on SAPT suggests that the sources of interaction energies differ for the two configurations TCR and TNR. For TCR, the induction energy is the primary contributor, for TNR, the electrostatic interaction dominates. Our comprehensive study not only enhances our understanding of the intricate interactions between H2 and C3N but also serves as a valuable guide for enhancing the adsorption strength in physical hydrogen storage systems.

R2Pt7MnP4-x (R = Ca, Eu): Intrinsic heterostructures based on a combination of AuCu3- and CaBe2Ge2-type fragments with chemically switchable magnetic interplay

Two quaternary phosphide platinides, Eu2Pt7MnP2.96 (I4/mmm, a = 4.0453(7) Å, c = 26.745(4) Å, V = 437.67(17) Å3, Z = 2, R1 = 0.0262, wR2 = 0.0527) and Ca2Pt7MnP3.02 (I4/mmm, a = 4.0027(5) Å, c = 26.735(5) Å, V = 428.34(14) Å3, Z = 2, R1 = 0.0280, wR2 = 0.0673) were synthesized as single crystals and bulk samples, their crystal structures were established from single-crystal X-ray diffraction data and confirmed by powder diffraction and elemental analysis. The compounds crystallize in the tetragonal system, and represent heterostructures built from the alternating layers of AuCu3- and CaBe2Ge2-type fragments. Both compounds are metallic based on the DFT calculations. Chemical bonding analysis reveals a pattern of covalent and ionic interactions within each compound. Magnetic measurements show both compounds to be ferromagnetic, and reveal an interplay between europium and manganese magnetic lattices, indicative of an exchange bias effect.

Aluminum Fluorides as Noncovalent Lewis Acids in Proteins: The Case of Phosphoryl Transfer Enzymes.

The Protein Data Bank (PDB) was scrutinized for the presence of noncovalent O ⋅ ⋅ ⋅ Al Triel Bonding (TrB) interactions, involving protein residues (e. g. GLU and GLN), adenosine/guanine diphosphate moieties (ADP and GDP), water molecules and two aluminum fluorides (AlF3 and AlF4 -). The results were statistically analyzed, revealing a vast number of O ⋅ ⋅ ⋅ Al contacts in the active sites of phosphoryl transfer enzymes, with a marked directionality towards the Al σ-/π-hole. The physical nature of the TrBs studied herein was analyzed using Molecular Electrostatic Potential (MEP) maps, the Quantum Theory of Atoms in Molecules (QTAIM), the Non Covalent Interaction plot (NCIplot) visual index and Natural Bonding Orbital (NBO) studies. As far as our knowledge extends, it is the first time that O ⋅ ⋅ ⋅ Al TrBs are analyzed within a biological context, participating in protein trapping mechanisms related to phosphoryl transfer enzymes. Moreover, since they are involved in the stabilization of aluminum fluorides inside the protein's active site, we believe the results reported herein will be valuable for those scientists working in supramolecular chemistry, catalysis and rational drug design.