Non-conventional Interactions Research Articles

Unveiling the mechanism and regioselectivity of the [3 + 2] cycloaddition reaction between N-methylphenylnitrone and 1-sulphonyl-1-trifluoromethylallene. A MEDT study

The present study reports within the molecular electron density theory the mechanism and the selectivity of the [3 + 2] cycloaddition (32CA) reaction between an N-methyl-phenylnitrone (nitrone 5) toward the poorest electrophile1-sulphonyl-1-trifluoromethylallene (allene 6) using DFT method at the B3LYP/6-31G(d) theoretical level. Four reactive pathways associated with the ortho and meta regioselective channels and endo and exo stereoselective approaches modes have been explored and characterised. While the formation of the meta/exo cycloadduct as the major isomer proceeds via a stepwise mechanism with the participation of zwitterion intermediate. Whereas, the other three pathways follow a one-step mechanism, the conceptual DFT reactivity indices analysis explains correctly the polar character of this 32CA reaction, and the local Parr functions analysis enables us to explain the meta-regioselectivity observed experimentally. The presence of both trifluromethyl and sulphonyl as electron-withdrawing groups increase markedly the reactivity of the allene and produces the meta selectivity. The inclusion of the solvent effects does not modify the obtained gas-phase selectivities but slightly increases the activation energies as well as the meta-exo stereoselectivity. QTAIM analyse reveal that the presence of significant numbers of conventional and non-conventional interactions at both TSs of the most favourable meta channel is responsible for the complete regioselectivity observed experimentally at this 32CA reaction.

Effect of capillary pressure on the CO2 flux in the pores of membrane contactor: Theory and simulation results

A simulation model was made to evaluate the effect of the capillary pressure on the CO2 capture by membrane absorption. More specifically, the model calculated the changes in the interfacial pressure and CO2 flux as the interface of gas and liquid moves through the pore opening to its exit. Two cases were considered; hydrophilic or hydrophobic membrane materials with a respective contact angle of less or more than 90°. It was revealed that CO2 flux is about 70% higher for the hydrophilic membrane of 10−6 m radius and 50 × 10−6 m length than the hydrophobic membrane of equal pore radius and pore length, when nearly equal to 1.72 × 105 Pa is applied either on the feed side (hydrophilic membrane) or on the permeate side (hydrophobic membrane) to keep the membrane pore dry without gas bubble formation. It should be noted that CO2 flux is higher when a hydrophilic membrane is used, which is against the common belief that a hydrophobic membrane is preferable for membrane absorption. Also, the duration for the interface to get to the pore exit was determined. The effect of capillary pressure increases as the membrane pores become smaller, which turns into an increase in CO2 flux when the porosity and the pore length are maintained constant. It was also revealed that the CO2 flux can be significantly increased when water absorbent is replaced by 1 M monoethanolamine solution due to increased CO2 solubility. Thus, this work is the first attempt to study the effect of capillary pressure on the flux of membrane contactors. It is recommended to collect more data on membrane contactors by the hydrophilic membrane. Electronic structure calculations were also performed to investigate the reaction mechanism between CO2 and MEA, with a focus on non-conventional interactions such as hydrogen bonding and van der Waals interactions. This is to know the details of the reaction occurring between CO2 and MEA.

Pactolo Bar: An Approach to Mitigate the Midas Touch Problem in Non-Conventional Interaction.

New ways of interacting with computers is driving research, which is motivated mainly by the different types of user profiles. Referred to as non-conventional interactions, these are found with the use of hands, voice, head, mouth, and feet, etc. and these interactions occur in scenarios where the use of mouse and keyboard would be difficult. A constant challenge in the adoption of new forms of interaction, based on the movement of pointers and the selection of interface components, is the Midas Touch (MT) problem, defined as the involuntary action of selection by the user when interacting with the computer system, causing unwanted actions and harming the user experience during the usage process. Thus, this article aims to mitigate the TM problem in interaction with web pages using a solution centered on the Head Tracking (HT) technique. For this purpose, a component in the form of a Bar was developed and inserted on the left side of the web page, called the Pactolo Bar (PB), in order to enable or disable the clicking event during the interaction process. As a way of analyzing the effectiveness of PB in relation to TM, two stages of tests were carried out based on the collaboration of voluntary participants. The first step aims to find the data that would lead to the best configuration of the BP, while the second step aims to carry out a comparative analysis between the PB solution and the eViacam software, whose use is also focused on the HT technique. The results obtained from the use of PB were considered promising, since the analysis of quantitative data points to a significant prevention of involuntary clicks in the iteration interface and the analysis of qualitative data showed the development of a better user experience due to the ease of use, which can be noticed in elements such as the PB size, the triggering mechanism, and its positioning in the graphical interface. This study benefits in the context of the user experience, because, when using non-conventional interactions, basic items such as aspects of the graphic elements, and interaction events raise new studies that seek to mitigate the problem of the Midas Touch.

A Tetranuclear Ni(II)-Cubane Cluster Molecule Build by Four µ3-O-Methanolate (MeO) Ligands, Externally Cohesive by Four Unprecedented Bridging µ2-N7,O6-Acyclovirate (acv-H) Anions

Metal ion interactions with nuclei acids and their constituents represent a multi-faceted and growing research field. This contribution deals with molecular recognition between synthetic purine 17 nucleosides and first-row transition metal complexes, with O- and/or N-amino chelators which are able to 18 engage in intra-molecular N-H···(N or O) and O-H···(N or O) interligand interactions. Crystals of these complexes can also display inter-molecular aromatic π-stacking and/or other non-conventional interactions. In this manuscript, we used 2-(2-aminoethoxy)ethanol (2aee) as a potential N,O(e),O(ol)-chelator for nickel(II). However, unexpectedly, the reaction between NiCl2, acyclovir (acv), and 2aee in methanol afforded parallelepiped apple-green crystals of [Ni(acv-H)(MeO)(H2O)]4·8H2O, (1) a tetranuclear molecule with an equimolar Ni(II):µ3-methanolate(1-):µ2-N7,O6-acyclovirate(1-) (acv-H) ratio. The µ2-N7,O6-(acv-H) metal-binding pattern (MBP) is unprecedented in terms of both its anionic and bridging roles. The single-crystal X-ray diffraction structure as well as thermogravimetric analysis and the (FT-IR +Vis-UV) spectra of 1 are reported. Theoretical density functional theory (DFT) calculations are used to analyse the antiparallel π-stacking interactions that govern the formation of self-assembled dimers in the solid state.

η3-allyl-Pd(II) complexes of 2-, 3- and 4-pyridylmethyl-coumarin esters

A series of 2-, 3- and 4-pyridylmethyl-coumarin esters ligands (1–3) and their η3-allyl palladium complexes (1-Pd–3-Pd) have been designed, synthetized, and characterized. NMR analysis of compounds 1-Pd–3-Pd indicated the presence of the allyl fragment. The molecular structures of 2, 3 and 1-Pd were determined by X-ray crystallographic analysis. The molecular structure of 1-Pd reveals that coumarin ligand (2) is coordinated to the palladium center via a monodentate fashion through the nitrogen atom of the pyridinyl fragment while, the allyl group is binding via a η3 fashion in an overall square-planar geometry completed with a chloride atom. The crystal packing is stabilized by a variety of weak intermolecular conventional and non-conventional interactions involving C–H–O/N hydrogen bonds, π–π and C–H–π interactions, which have been analyzed by Hirshfeld surface and non-covalent interactions analysis. The intermolecular interaction energies were explored using an energy framework analysis, which revealed that π–π and C–H–π interactions serve as the primary building blocks in these crystal packing.Graphical abstract

New hydrate cocrystal of l-proline with 4-acetylphenylboronic acid obtained via mechanochemistry and solvent evaporation: An experimental and theoretical study

In this work, we present the formation of a new multi-component molecular complex by targeting the boronic acid moiety (-B(OH)2) of 4-acetylphenylboronic acid with the carboxylate group (-COO-) of l-proline using two different techniques: mechanochemistry and solvent evaporation. The experiments produced efficiently a new cocrystal named L-PRO4APBA. It was characterised to study its structural properties by X-ray powder diffraction (XRPD), infrared spectroscopy (FTIR), single-crystal X-ray diffraction (SCXRD), and quantum chemical methods based on QTAIM. Also, its thermal behaviour was analysed using a simultaneous DSC/TGA experiment. The results showed that L-PRO4APBA comprises discrete molecular units held together mainly by O–H⋯O and N–H⋯O hydrogen bonds. However, C–H⋯O, C–H⋯π, and other non-conventional interactions gave further stabilisation. Moreover, SCXRD showed that the asymmetric unit contains five independent molecules: two of l-proline (PRO1 and PRO2), two of 4-acetylphenylboronic acid (4APBA1 and 4APBA2) and one of water. PRO1 and PRO2 adopted different conformations with their carboxylate groups in equatorial and axial positions, respectively. This feature produced two independent helical chains running along the 21 screw axis in which 4APBA1 and 4APBA2 bound through the expected -B(OH)2···−OOC- heterosynthon. Surprisingly, the presence of water molecules in the lattice did not disrupt the formation of this motif. However, water molecules played an essential role for the stabilisation of the 3D structure. These findings would set up the structural basis to continue exploring the formation of new cocrystals by combining l-proline with boronic acids.

Sensing and photocatalytic properties of a new 1D Zn(II)-based coordination polymer derived from the 3,5-dibromosalicylaldehyde nicotinoylhydrazone ligand

A new 1D coordination polymer, [Zn(dsn)(HO2CCH3)]n (1), has been synthesized by reacting the Schiff base ligand 3,5-dibromosalicylaldehyde nicotinoylhydrazone (H2dsn) with Zn(O2CCH3)2·6H2O. The polymer has been characterized using FTIR spectroscopy and single crystal X-ray diffraction analysis. The single crystal X-ray analysis reveals that the immediate geometry around the Zn(II) ion is five-coordinate, that is satisfied by a pyridyl nitrogen atom of one dsn ligand, the imine-N, carbonyl-O and phenoxo-O atoms of the other dsn ligand, as well as the acetate oxygen atom, which generate a trigonal bipyramidal geometry. Furthermore, the dsn ligand coordinated by the pyridyl nitrogen atom also coordinates to another Zn(II) ion by its imine-N, carbonyl-O and phenoxo-O atoms to generate a zig-zag lD polymer chain. The 1D chain is held by weak non-conventional interactions in the solid state to engender a 2D supramolecular layer. The photoluminescent (PL) property of 1 has been investigated and the polymer has been exploited as a sensitive and selective fluorescent sensor to detect metronidazole (MDZ) with limit of detection (LOD) of 9.39 × 10−7 M amongst a variety of related antibiotics. Also, 1 has been used as a photocatalyst and displays excellent photocatalytic degradation of methylene blue (MB), decomposing 86.3% in 100 min under UV light irradiation. The plausible mechanisms which polymer 1 executed for the sensing of MDZ and photodegradation of MB have been explained with the aid of theoretical calculations.

Thermodynamic Properties of the Superconducting State in Metallic Hydrogen: Electronic Correlations, Non-conventional Electron-Phonon Couplings and the Anharmonic Effects

Thermodynamical properties of the superconducting state in metallic hydrogen were determined on the basis of the model of two compressed hydrogen planes. We took into account both the on-site and the inter-site electronic correlations (U and K), as well as the relevant non-conventional electron-phonon coupling functions (gU and gK). We proved, within the Eliashberg formalism, that the maximum value of the critical temperature of transition into the superconducting state is about 200 K for the harmonic approximation, and about 84 K for the Morse anharmonic approximation. Omission of the electronic correlations results in a considerable overstatement of the TC value. On the other hand, the TC value is remarkably understated if the non-conventional interactions are disregarded. Other thermodynamic quantities, such as the order parameter, the jump in the specific heat value, the thermodynamic critical field, and the upper critical field, take the values for which the non-dimensional ratios RΔ, RC, RH and RH2 do not differ substantially from the predictions of the BCS theory.

A “nucleophilic” iodine in a halogen-bonded iodonium complex manifests an unprecedented I+···Ag+ interaction

Summary When an electron is removed from a halogen atom, it forms a halenium ion X+ (X = I, Br, Cl). In halogen bonding (XB), X+ is considered as a strong XB donor, and when interacting with two XB acceptors (e.g., pyridine), it forms a halonium XB complex with a [N–I–N] three-center-four-electron bond with the two XB acceptors. An unprecedented I+···Ag+ interaction occurs between a [L1–I–L1]+ halogen-bonded complex and a [L2–Ag–L2]+ complex in which the iodonium ion acts like a nucleophile and donates electrons to the silver(I) cation. The X-ray diffraction analysis reveals a short contact [3.4608(3) A] between the I+ and Ag+ cations, and ITC measurements give a ΔG of −6.321 kcal/mol and Ka∼37,000 M−1 for the 1:1 complex. The DFT computational study on the nature of the I+···Ag+ interaction indicates that the I+ is nucleophilic in character, manifesting an unusual and strongly attractive interaction between the I+ and Ag+ cations.

Non-conventional interactions of N3 inhibitor with the main protease of SARS-CoV and SARS-CoV-2

The extensive spread of COVID-19 in every continent shows that SARS-CoV-2 virus has a higher transmission rate than SARS-CoV virus which emerged in 2002. This results in a global pandemic that is difficult to control. In this investigation, we analyze the interaction of N3 inhibitor and the main protease of SARS-CoV and SARS-CoV-2 by quantum chemistry calculations. Non-covalent interactions involved in these systems were studied using a model of 469 atoms. Density Functional Theory and Quantum Theory of Atoms in Molecules calculations lead us to the conclusion that non-conventional hydrogen bonds are important to describe attractive interactions in these complexes. The energy of these non-conventional hydrogen bonds represents more than a half of the estimated interaction energy for non-covalent contacts. This means that hydrogen bonds are crucial to correctly describe the bonds between inhibitors and the main proteases. These results could be useful for the design of new drugs, since non-covalent interactions are related to possible mechanisms of action of molecules used against these viruses.

A molecular interaction field describing nonconventional intermolecular interactions and its application to protein–ligand interaction prediction

Nonconventional noncovalent interactions such as CH/O, CH/π, and halogen bonds play important roles in molecular recognition in biological systems and have been increasingly exploited in structure-based drug design. In silico approaches that consider these interactions would be an effective strategy for drug discovery. The computation of the molecular interaction field (MIF), which is a three-dimensional (3D) potential map describing the interactions formed around a target compound, would assist the design of molecules that bind to the target biomolecule via nonconventional interactions. In this study, we developed a novel MIF calculation method that describes nonconventional interactions. This method evaluates the MIF as the interaction energy between the target ligand molecule and probe molecule. To describe the nonconventional interactions, our method employs quantum chemical calculations with four types of probe molecules. The calculated MIFs for casein kinase 2 (CK2) inhibitors correctly identify the halogen bond, CH/π, and CH/O interactions formed in the CK2/inhibitor complexes. Additionally, we have developed a method for calculating the protein–ligand interaction energy (Eint) based on the MIF and a coarse-grained protein model. The calculated interaction energies for CK2 inhibitors correlate with the experimental log(Ki) values. Thus, MIF and Eint obtained by our method show promise as descriptors for protein-ligand interaction prediction by considering nonconventional noncovalent interactions.

Unravelling the mechanism and the origin of the selectivity of the [3 + 2] cycloaddition reaction between electrophilic nitrone and nucleophilic alkene

In this paper, we have studied within the molecular electron density theory the mechanism and the origin of the selectivity of the [3 + 2] cycloaddition reaction between electrophilic nitrone 1 and nucleophilic alkene, indole 2, using DFT method at the B3LYP/6-31G(d) theoretical level. The obtained results clearly indicated that this reaction is characterised by an ortho regioselectivity and an exo stereoselectivity. Inclusion of the solvent effects does not modify the obtained gas-phase selectivities but slightly increase the activation energies. The analysis of the geometries of the transition states with bond order and global electron density transfer shows that this reaction takes place via a slightly asynchronous non-polar one-step mechanism. Analysis of the electronic structure of nitrone 1 indicates that this species has a zwitterionic-type structure that enables its participation in zw-type 32CA reactions. Conceptual DFT reactivity indices analysis confirms the highly obtained activation energies and local Parr functions analysis allows us to explain the ortho regioselectivity of this 32CA reaction. NCI, ESP and QTAIM analyses indicate that the presence of several conventional and non-conventional interactions at the structure of the most favourable approach ortho–exo is the origin for the selectivity of this 32CA reaction.

Novel diastereoisomers of C21H20O3 obtained from the cathodic reduction of methyl (2E)-3-[2-(2-{2-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}ethyl)phenyl]prop-2-enoate

Abstract The diastereoisomeric title compounds, 5 and 6, were obtained as a result of intramolecular electrohydrocyclisation of methyl (2E)-3-[2-(2-{2-[(1E)-3-methoxy-3-oxoprop-1-en-1-yl]phenyl}ethyl)phenyl]prop-2-enoate. The common feature of the molecular structures is the presence of a central, eight-membered, –C(H)–C(H)–CC–(CH2)2–CC, ring appended to a cyclopentenyl and two phenyl rings. This study represents an unprecedented structural characterisation of such an atomic/bonding arrangement. The distinctive feature of the structures relates to the conformation of the central rings, i.e. approximating a boat in 5 and a chair in 6. This difference in molecular conformations arises from the different configurations at the methine-C atoms of the cyclopentenyl ring, i.e. R- and S- (or S- and R-) in 5 as opposed to R- and R- (or S- and S-) in 6. In each case, the hydroxyl-OH forms an intramolecular hydrogen-bond to the adjacent carbonyl-O atom so the molecular packing in each of 5 and 6 is sustained by non-conventional interactions. A three-dimensional architecture in 5 arises from a combination of phenyl-C–H…O(carbonyl) and methyl- and methylene-C–H…π contacts. In the crystal of 6, supramolecular chains with a zig-zag topology along the c-axis are formed via methyl-C–H…O(hydroxyl); the chains pack with no directional interactions between them.

MiRepress: modelling gene expression regulation by microRNA with non-conventional binding sites.

Some earlier studies have reported an alternative mode of microRNA-target interaction. We detected target regions within mRNA transcripts from AGO PAR-CLIP that did not contain any conventional microRNA seed pairing but only had non-conventional binding sites with microRNA 3′ end. Our study from 7 set of data that measured global protein fold change after microRNA transfection pointed towards the association of target protein fold change with 6-mer and 7-mer target sites involving microRNA 3′ end. We developed a model to predict the degree of microRNA target regulation in terms of protein fold changes from the number of different conventional and non-conventional target sites present in the target, and found significant correlation of its output with protein expression changes. We validated the effect of non-conventional interactions with target by modulating the abundance of microRNA in a human breast cancer cell line MCF-7. The validation was done using luciferase assay and immunoblot analysis for our predicted non-conventional microRNA-target pair WNT1 (3′ UTR) and miR-367-5p and immunoblot analysis for another predicted non-conventional microRNA-target pair MYH10 (coding region) and miR-181a-5p. Both experiments showed inhibition of targets by transfection of microRNA mimics that were predicted to have only non-conventional sites.

Supramolecular assemblies of Ru(ii) organometallic half-sandwich complexes

Extended hydrogen bonding network in [(arene)Ru(para-substituted amine ligand)Cl2].

Five new metal(II) complexes with 3-D network structures based on carboxylate and bis(imidazole) ligands: syntheses and structures

The imidazolyl ligands, bis(N-imidazolyl)methane (L1) and 1,4-bis(N-imidazolyl)butane (L2) reacted with Zn(II), Cu(II), and Ni(II) salts of carboxylic acids resulting in the formation of five metal–organic coordination architectures, [Zn(L1)(CO3)] · H2O (1), [Cu(L2)(cnic)2] · H2O (2) (cnic = 2-chloronicotinate), [Cu2(L2)2(adip)2] · 6H2O (3) (adip = adipate), [Ni(mal)(L1)(H2O)] (4) (mal = malonate), and [Ni3(ctc3 − )2(L1)6] · 35H2O (5) (ctc − = citrate). All complexes have been characterized by elemental analysis, infrared, TG, and X-ray diffraction analyses. The different coordination modes of the carboxylates due to their chain length and rigidity lead to a range of different coordination structures. All these complexes display 3-D framework structures with a number of non-conventional weak interactions. The carboxylates can adopt bridging μ 2, chelating μ 2, chelating-bridging μ 3, and chelating μ 3 coordination modes. The metals are coordinated in N2O2, N2O3, N2O4, N3O3, and N6 fashions depending on the metal and ancillary ligands. The frameworks of the five compounds are thermally stable.

Six hydrogen bond directed supramolecular adducts formed between racemic-bis-β-naphthol and N-containing aromatic bases

Abstract Studies concentrating on hydrogen bonding between the base of exobidentate bis(imidazole) derivatives, and 2-aminoheterocyclic compounds, and (±)-1,10-binaphthalene-2,2′-diol have led to an increased understanding of the role the aromatic N-containing compounds have in binding with (±)-1,10-binaphthalene-2,2′-diol. Here anhydrous multicomponent adducts of N-containing aromatic bases such as 1,4-bis(N-imidazolyl)butane (L1), 1,3-bis(N-benzimidazolyl)propane (L2), 1,4-bis(N-benzimidazolyl)butane (L3), 1,5-bis(N-benzimidazolyl)-3-oxapentane (L4), 2-amino-4-phenylthiazole (L5), and 2-amino-5,7-dimethyl-1,8-naphthyridine (L6) have been prepared with (±)-1,10-binaphthalene-2,2′-diol (binol). The six crystalline forms reported are cocrystals of which the crystals and complexes were characterized by X-ray diffraction analysis, IR, mp, and elemental analysis. The inter-ring angles (naphthol/naphthol) in the same binol of the six cocrystals ranged from 70.71° to 104.2° as the organic bases varied. In the six cocrystals, the binols exist either as both of the enantiomers of rac-binol or as only of its single enantiomer. All supramolecular architectures of cocrystals 1–6 are stabilized by O–H⋯N hydrogen bonds. In addition other non-conventional interactions (CH–π, CH3–π, NH–π, S–π, and π–π interactions) play an important role in the solid-state packing of co-crystallization as well. These weak interactions combined, all of the six complexes displayed 3D network structure.

A compact review on the comparison of conventional and non-conventional interactions on the structural stability of therapeutic proteins

Therapeutic proteins carry out the most difficult tasks in living cells. They do so by interacting specifically with other molecules. This requires that they fold to a unique and more stable conformation. A prerequisite for comprehending the folding processes in their immense complexity entails a thorough understanding of many weak interactions. The purpose of this review is to systematically study the role of weak interactions such as cation-π, C-H......π, N-H......π and O-H......π, in the set of 49 therapeutic proteins. The importance of many of these interactions (for example, cationic residues interacting with π system) is revealed by the higher degree of conservation observed for them in protein structures. These interactions are mainly formed by long-range contacts and significant percentage of cation-π, C-H......π, N-H......π and O-H......π interacting residues had one or more stabilization centers. Further, a comparison of conventional and nonconventional interactions in the present data set unambiguously highlights the significance of these weak interactions in the structural stability of therapeutic proteins. We propose that the incorporation of the entirety of these interactions leads to a more complete description of the problem, and that this could provide new perspectives and new possible answers.

Synthesis and structural characterization of three saccharinate–metal complexes with exo-bidentate bis(imidazole) derivatives

Three coordination compounds, [Ag2(L1)(sac)2] · 5(H2O) (1, L1 = bis(N-imidazolyl)methane, sac = saccharinate), [Ag(L2)(sac)], (2, L2 = 1,4-bis(N-imidazolyl)butane), and [Cu(L2)2(H2O)2](sac)2 · 2(H2O) (3), were obtained from self-assembly of the metal salts with bis-imidazole ligands in the presence of saccharinato ion. All products were formed in solution and obtained by slow evaporation. Their structures were fully characterized by X-ray diffraction (XRD) analysis, Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analyses. Compound 1 is a linear dinuclear complex, consisting of two Ag(sac) units bridged by a bis(N-imidazolyl)methane, while 2 is a tri-coordinated Ag(I) complex, with Ag(I) surrounded by three nitrogens in trigonal plane geometry. Compound 2 displays a 1-D wavy chain structure. XRD analysis revealed that 3 exhibits 1-D cationic double-stranded chain structure from doubly bridged [Cu(H2O)2] units. All these complexes display 3-D framework structures from a number of non-conventional weak interactions. IR spectra, elemental analyses, and thermal analyses are in good agreement with the crystal structure.

Contribution of unconventional C-H…O bonds to the structural stability of Antimicrobial peptides

The native structure of Antimicrobial peptides is stabilized by a large number of individually weak forces; a complete understanding of folding implies the need to evaluate the contribution of each of these, including nonconventional hydrogen bonds. In this work, we have analyzed the influence of C-H...O interactions in the structural stability of Antimicrobial peptides by comparison with conventional hydrogen bond. There are a number of amino acid residues that can form hydrogen bonds via their side chains in addition to their peptide group. Perhaps highest contribution in this category is polar residue (Cys) and charged residues such as Lys and Arg. A total of 2513 C-H...O interactions were found in a data set of 53 Antimicrobial peptides. Among the 2513 nonconventional interactions observed in the data set, 40% of interactions are bonded to alpha carbon. This is consistent with the fact that the hydrogens are more acidic than others. Most prominent were side-chain to main-chain C-H...O interactions (SM-C-H...O). 92% of the stabilizing centers in the Antimicrobial peptides were found to be involved in C-H...O interactions. These interactions are mainly formed by short range contacts. Moreover, the study shows that, there is an average of more than one C-H...O interactions observed for every single residue in the Antimicrobial peptides data set. It is concluded that the C-H...O interaction can, indeed, be categorized as a true stabilizing force like hydrogen bond in Antimicrobial peptides.