Noncovalent Complexes Research Articles

Physicochemical properties, antioxidant activities, and binding behavior of 3,5-di-O-caffeoylquinic acid with beta-lactoglobulin colloidal particles

Milk proteins and polyphenols are increasingly being studied as functional ingredients due to the epidemiologically-proved health benefits. In this study, composite β-lactoglobulin (β-lg) or β-lactoglobulin nanoparticles (β-lgNPs)-3,5-di-O-caffeoylquinic acid (3,5diCQA) with superior physicochemical and antioxidant activity (AA) were produced using β-lg and 3,5-di-O-caffeoylquinic acid. The main interactions between β-lg or β-lgNPs with 3,5diCQA were hydrogen bonding and hydrophobic effects. The 3,5diCQA caused a decrease in α-helix and β-sheet structure with a corresponding increase in unordered structure. Compared to β-lg alone, composite β-lg or β-lgNPs-3,5diCQA slightly decreased the particle size but increased their negative surface potentials especially for β-lg or β-lgNPs at a molar ratio of 5:1. The addition of 3,5diCQA appreciably improved the AA in a dose-dependent manner. These results shed light on the structural, physicochemical, and AA of composite β-lg or β-lgNPs-3,5diCQA non-covalent complexes, important for application as functional ingredients in food solutions as well as in the pharmaceutical industry.

Identification of the Primary Factors Determining theSpecificity of Human VKORC1 Recognition by Thioredoxin-Fold Proteins.

Redox (reduction–oxidation) reactions control many important biological processes in all organisms, both prokaryotes and eukaryotes. This reaction is usually accomplished by canonical disulphide-based pathways involving a donor enzyme that reduces the oxidised cysteine residues of a target protein, resulting in the cleavage of its disulphide bonds. Focusing on human vitamin K epoxide reductase (hVKORC1) as a target and on four redoxins (protein disulphide isomerase (PDI), endoplasmic reticulum oxidoreductase (ERp18), thioredoxin-related transmembrane protein 1 (Tmx1) and thioredoxin-related transmembrane protein 4 (Tmx4)) as the most probable reducers of VKORC1, a comparative in-silico analysis that concentrates on the similarity and divergence of redoxins in their sequence, secondary and tertiary structure, dynamics, intraprotein interactions and composition of the surface exposed to the target is provided. Similarly, hVKORC1 is analysed in its native state, where two pairs of cysteine residues are covalently linked, forming two disulphide bridges, as a target for Trx-fold proteins. Such analysis is used to derive the putative recognition/binding sites on each isolated protein, and PDI is suggested as the most probable hVKORC1 partner. By probing the alternative orientation of PDI with respect to hVKORC1, the functionally related noncovalent complex formed by hVKORC1 and PDI was found, which is proposed to be a first precursor to probe thiol–disulphide exchange reactions between PDI and hVKORC1.

Tandem surface-induced dissociation of protein complexes on an ultrahigh resolution platform

We describe instrumentation for conducting tandem surface-induced dissociation (tSID) of native protein complexes on an ultrahigh resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The two stages of SID are accomplished with split lenses replacing the entrance lenses of the quadrupole mass filter (stage 1, referred to herein as SID-Q) and the collision cell (stage 2, Q-SID). After SID-Q, the scattered projectile ions and subcomplexes formed in transit traverse the pre-filter prior to the mass-selecting quadrupole, providing preliminary insights into the SID fragmentation kinetics of noncovalent protein complexes. The isolated SID fragments (subcomplexes) are then fragmented by SID in the collision cell entrance lens (Q-SID), generating subcomplexes of subcomplexes. We show that the ultrahigh resolution of the FT-ICR can be used for deconvolving species overlapping in m/z, which are particularly prominent in tandem SID spectra due to the combination of symmetric charge partitioning and narrow product ion charge state distributions. Various protein complex topologies are explored, including homotetramers, homopentamers, a homohexamer, and a heterohexamer.

Oral insulin delivery using artificial peptide

The daily multiple insulin injection is the line of treatment for diabetes mellitus. As the oral insulin delivery mimics, the physiology of endogenous insulin secreted by pancreas. Recently, the search for suitable carrier to develop oral insulin delivery has been intensified. However, the carrier toxicity and very less bioavailability of insulin remains the major problem in the development of oral insulin delivery. Preparation of a non-covalent insulin-peptide complex using different peptide made of 16 to 20 L-amino acids studied to overcome the problem. The in vitro testing of insulin-peptide complex showed significant stability against the proteolytic enzyme. Whereas, in in vivo testing, the presence of 10-41% insulin in blood plasma observed after 30 to 60 min oral feeding of insulin-peptide complex. Results indicated that the peptide which showed moderate protection against pepsin and minor protection against trypsin and chymotrypsin has an important role in enhancing oral insulin bioavailability. However, the peptide which showed higher protection against trypsin and no protection against pepsin could not achieve significant oral insulin bioavailability.

Characterization of the T4 gp32-ssDNA complex by native, cross-linking, and ultraviolet photodissociation mass spectrometry.

Protein–DNA interactions play crucial roles in DNA replication across all living organisms. Here, we apply a suite of mass spectrometry (MS) tools to characterize a protein-ssDNA complex, T4 gp32·ssDNA, with results that both support previous studies and simultaneously uncover novel insight into this non-covalent biological complex. Native mass spectrometry of the protein reveals the co-occurrence of Zn-bound monomers and homodimers, while addition of differing lengths of ssDNA generates a variety of protein:ssDNA complex stoichiometries (1 : 1, 2 : 1, 3 : 1), indicating sequential association of gp32 monomers with ssDNA. Ultraviolet photodissociation (UVPD) mass spectrometry allows characterization of the binding site of the ssDNA within the protein monomer via analysis of holo ions, i.e. ssDNA-containing protein fragments, enabling interrogation of disordered regions of the protein which are inaccessible via traditional crystallographic techniques. Finally, two complementary cross-linking (XL) approaches, bottom-up analysis of the crosslinked complexes as well as MS1 analysis of the intact complexes, are used to showcase the absence of ssDNA binding with the intact cross-linked homodimer and to generate two homodimer gp32 model structures which highlight that the homodimer interface overlaps with the monomer ssDNA-binding site. These models suggest that the homodimer may function in a regulatory capacity by controlling the extent of ssDNA binding of the protein monomer. In sum, this work underscores the utility of a multi-faceted mass spectrometry approach for detailed investigation of non-covalent protein-DNA complexes.

Guanidine as a strong CO2 adsorbent: a DFT study on cooperative CO2 adsorption.

Among the various carbon capture and storage (CCS) technologies, the direct air capture (DAC) of CO2 by engineered chemical reactions on suitable adsorbents has attained more attention in recent times. Guanidine (G) is one of such promising adsorbent molecules for CO2 capture. Recently Lee et al. (Phys. Chem. Chem. Phys., 2015, 17, 10925-10933) reported an interaction energy (ΔE) of -5.5 kcal mol-1 for the GCO2 complex at the CCSD(T)/CBS level, which was one of the best non-covalent interactions observed for CO2 among several functional molecules. Here we show that the non-covalent GCO2 complex can transform to a strongly interacting G-CO2 covalent complex under the influence of multiple molecules of G and CO2. The study, conducted at M06-2X/6-311++G** level density functional theory, shows ΔE = -5.7 kcal mol-1 for GCO2 with an NC distance of 2.688 Å while almost a five-fold increase in ΔE (-27.5 kcal mol-1) is observed for the (G-CO2)8 cluster wherein the N-C distance is 1.444 Å. All the (G-CO2)n clusters (n = 2-10) show a strong N-CO2 covalent interaction with the N-C distance gradually decreasing from 1.479 Å for n = 2 to 1.444 Å for n = 8 ≅ 9, 10. The N-CO2 bonding gives (G+)-(CO2-) zwitterion character for G-CO2 and the charge-separated units preferred a cyclic arrangement in (G-CO2)n clusters due to the support of three strong intermolecular OHN hydrogen bonds from every CO2. The OHN interaction is also enhanced with an increase in the size of the cluster up to n = 8. The high ΔE is attributed to the large cooperativity associated with the N-CO2 and OHN interactions. The quantum theory of atoms in molecules (QTAIM) analysis confirms the nature and strength of such interactions, and finds that the total interaction energy is directly related to the sum of the electron density at the bond critical points of N-CO2 and OHN interactions. Further, molecular electrostatic potential analysis shows that the cyclic cluster is stabilized due to the delocalization of charges accumulated on the (G+)-(CO2-) zwitterion via multiple OHN interactions. The cyclic (G-CO2)n cluster formation is a highly exergonic process, which reveals the high CO2 adsorption capability of guanidine.

Photoinduced electron transfer in non-covalent complexes of C60 and phosphangulene oxide derivatives.

Investigation of photoinduced electron transfer (PET) in a series of experimentally reported complexes of fullerene with phosphangulene oxides shows that the replacement of O atoms in the bridge of phosphangulene with S atoms promotes efficient and ultrafast ET from phosphangulene oxide to fullerene in PGOOSS⊃C60 and PGOSSS⊃C60 complexes. The results obtained can be useful for the development of photovoltaic devices based on phosphangulenes.

Mechanistic and thermodynamic characterization of oxathiazolones as potent and selective covalent immunoproteasome inhibitors

The ubiquitin–proteasome system is responsible for the degradation of proteins and plays a critical role in key cellular processes. While the constitutive proteasome (cPS) is expressed in all eukaryotic cells, the immunoproteasome (iPS) is primarily induced during disease processes, and its inhibition is beneficial in the treatment of cancer, autoimmune disorders and neurodegenerative diseases. Oxathiazolones were reported to selectively inhibit iPS over cPS, and the inhibitory activity of several oxathiazolones against iPS was experimentally determined. However, the detailed mechanism of the chemical reaction leading to irreversible iPS inhibition and the key selectivity drivers are unknown, and separate characterization of the noncovalent and covalent inhibition steps is not available for several compounds. Here, we investigate the chemical reaction between oxathiazolones and the Thr1 residue of iPS by quantum mechanics/molecular mechanics (QM/MM) simulations to establish a plausible reaction mechanism and to determine the rate-determining step of covalent complex formation. The modelled binding mode and reaction mechanism are in line with the selective inhibition of iPS versus cPS by oxathiazolones. The kinact value of several ligands was estimated by constructing the potential of mean force of the rate-determining step by QM/MM simulations coupled with umbrella sampling. The equilibrium constant Ki of the noncovalent complex formation was evaluated by classical force field-based thermodynamic integration. The calculated Ki and kinact values made it possible to analyse the contribution of the noncovalent and covalent steps to the overall inhibitory activity. Compounds with similar intrinsic reactivities exhibit varying selectivities for iPS versus cPS owing to subtle differences in the binding modes that slightly affect Ki, the noncovalent affinity, and importantly alter kinact, the covalent reactivity of the bound compounds. A detailed understanding of the inhibitory mechanism of oxathiazolones is useful in designing iPS selective inhibitors with improved drug-like properties.

Binding of chloroaurate to polytyrosine-PEG micelles leads to an anti-Turkevich pattern of reduction.

Here we report formation of gold nanoparticles (GNPs) in micelles of polytyrosine-PEG copolymers that combine the properties of a reducer and a stabilizer. The size and properties of the GNPs were tailored by the excess chloroaurate over the copolymer. The latter quickly formed non-covalent complexes with HAuCl4 and then slowly reduced it to form GNPs. 3 Tyr residues are consumed by reduction of one mole of chloroaurate. The size of the GNPs was controlled by the [Tyr]/[Au(iii)] molar ratio. Small GNPs with D ≅ 8 nm were formed at [Tyr]/[Au(iii)] = 0.5-1.5. 90% of these small GNPs remained bound to the copolymer and could be stored in a lyophilized state. Such polypeptide-gold hybrid materials produced at [Tyr]/[Au(iii)] = 0.5 demonstrated high activity in the catalytic reduction of 4-nitrophenol by sodium borohydride. [Tyr]/[Au(iii)] = 5 led to the formation of large nanoplates (D ≅ 30-60 nm). Thus, in the polymer-based system the GNP size grew in line with the excess of the reducing agent in contrast to Turkevich synthesis of GNPs with citric acid, which also combines the functions of a stabilizer and a reducer. The difference results from the reduction of HAuCl4 in solution according to the Turkevich method and in the micelles of the amphiphilic polymer where the seed growth is limited by the amount of neighboring reducer.

Covalent flexible peptide docking in Rosetta.

Electrophilic peptides that form an irreversible covalent bond with their target have great potential for binding targets that have been previously considered undruggable. However, the discovery of such peptides remains a challenge. Here, we present Rosetta CovPepDock, a computational pipeline for peptide docking that incorporates covalent binding between the peptide and a receptor cysteine. We applied CovPepDock retrospectively to a dataset of 115 disulfide-bound peptides and a dataset of 54 electrophilic peptides. It produced a top-five scoring, near-native model, in 89% and 100% of the cases when docking from the native conformation, and 20% and 90% when docking from an extended peptide conformation, respectively. In addition, we developed a protocol for designing electrophilic peptide binders based on known non-covalent binders or protein–protein interfaces. We identified 7154 peptide candidates in the PDB for application of this protocol. As a proof-of-concept we validated the protocol on the non-covalent complex of 14-3-3σ and YAP1 phosphopeptide. The protocol identified seven highly potent and selective irreversible peptide binders. The predicted binding mode of one of the peptides was validated using X-ray crystallography. This case-study demonstrates the utility and impact of CovPepDock. It suggests that many new electrophilic peptide binders can be rapidly discovered, with significant potential as therapeutic molecules and chemical probes.

Fully Conjugated Pyrene-BODIPY and Pyrene-BODIPY-Ferrocene Dyads and Triads: Synthesis, Characterization, and Selective Noncovalent Interactions with Nanocarbon Materials.

Several pyrene-boron-dipyrromethene (BODIPY) and pyrene-BODIPY-ferrocene derivatives with a fully conjugated pyrene fragment appended to the α-position(s) of the BODIPY core have been prepared by Knoevenagel condensation reaction and characterized by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), UV-vis, fluorescence spectroscopy, high-resolution mass spectrometry as well as X-ray crystallography. The redox properties of new donor-acceptor BODIPY dyads and triads were studied by electrochemical (cyclic voltammetry (CV) and differential pulse voltammetry (DPV)) and spectroelectrochemical approaches. Formation of weakly bonded noncovalent complexes between the new pyrene-BODIPYs and nanocarbon materials (C60, C70, single-walled carbon nanotube (SWCNT), and graphene) was studied by UV-vis, steady-state fluorescent, and time-resolved transient absorption spectroscopy. UV-vis and fluorescent spectroscopy are indicative of the much stronger and selective interaction between new dyes and (6,5)-SWCNT as well as graphene compared to that of C60 and C70 fullerenes. In agreement with these data, transient absorption spectroscopy provided no evidence for any significant change in excited-state lifetime or photoinduced charge transfer between pyrene-BODIPYs and C60 or C70 fullerenes when the pyrene-BODIPY chromophores were excited into the lowest-energy singlet excited state. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations suggest that the pyrene fragments are fully conjugated into the π-system of BODIPY core, which correlates well with the experimental data.

Azanitrile Inhibitors of the SmCB1 Protease Target Are Lethal to Schistosoma mansoni: Structural and Mechanistic Insights into Chemotype Reactivity.

Azapeptide nitriles are postulated to reversibly covalently react with the active-site cysteine residue of cysteine proteases and form isothiosemicarbazide adducts. We investigated the interaction of azadipeptide nitriles with the cathepsin B1 drug target (SmCB1) from Schistosoma mansoni, a pathogen that causes the global neglected disease schistosomiasis. Azadipeptide nitriles were superior inhibitors of SmCB1 over their parent carba analogs. We determined the crystal structure of SmCB1 in complex with an azadipeptide nitrile and analyzed the reaction mechanism using quantum chemical calculations. The data demonstrate that azadipeptide nitriles, in contrast to their carba counterparts, undergo a change from E- to Z-configuration upon binding, which gives rise to a highly favorable energy profile of noncovalent and covalent complex formation. Finally, azadipeptide nitriles were considerably more lethal than their carba analogs against the schistosome pathogen in culture, supporting the further development of this chemotype as a treatment for schistosomiasis.

Study the structure and thermal properties of carboxymethylated-β-cyclodextrin inclusion complex with bifonazole

Recently, many technological methods of enhancing the solubility and dissolution characteristics of poorly water soluble drugs have been reported in the literature. Сyclodextrins are able to form water-soluble non-covalent inclusion complexes with many poorly soluble lipophilic drugs. The purpose of this study is to evaluate the possibility of interaction of the antifungal drug Bifonazole (BFZ) through complexation with carboxymethylated-β-cyclodextrin (КМ-β-CD). Based on the data obtained, we can conclude that the presence of KM-β-CD improves solubilization of BFZ more than 50 times. Кеуwords: cyclodextrins, solubility, poorly-water soluble drugs, bifonazole.

Hydrophilic Polyhedral Oligomeric Silsesquioxane, POSS(OH)32, as a Complexing Nanocarrier for Doxorubicin and Daunorubicin.

A novel strategy, recently developed by us, to use polyhedral oligomeric silsesquioxanes (POSS) as an anti-cancer drug carrier is presented. Anthracycline:POSS complexes were prepared by simple co-addition of doxorubicin (DOX) or daunorubicin (DAU) with hydrophilic POSS(OH)32. Co-delivery of POSS and anthracyclines led to higher anti-cancer activity towards HeLa (cervical cancer endothelial) and MCF-7 (human breast adenocarcinoma) cell lines. The obtained supramolecular hybrid complexes were characterised by nuclear magnetic resonance (NMR) spectroscopy (nuclear Overhauser effect spectroscopy [NOESY] and homonuclear correlation spectroscopy [COSY]), Fourier transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS). The two-dimensional (2D) NOESY spectra of the complexes showed the cross-correlation peaks for hydroxyl groups of POSS (~4.3–4.8 ppm) with OH groups of DOX and DAU. FTIR showed that hydroxyl group of POSS can interact with amine and hydroxyl groups of DOX and DAU. The viability of HeLa and MCF-7 was analysed with the MTT assay to evaluate the cytotoxicity of free DOX and DAU and the relevant complexes with POSS at different molar ratios. At a low DOX concentration (2.5 µM), for molar ratios 1:1, 1:4, and 1:8 (POSS:DOX), the complexes showed two and three times higher cytotoxicity towards HeLa and MCF-7 cells, respectively, than DOX itself after both 24- and 48-h incubation. The 1 µM concentration for a 1:4 POSS:DOX molecular ratio and the 2.5 µM concentration for all complexes were more toxic towards MCF-7 cells than free DOX after 48-h incubation. In the case of POSS:DAU complexes, there was higher toxicity than that of free drug after 48-h incubation. It can be concluded that the formation of non-covalent complexes increases toxicity of anthracycline drugs towards Hela and MCF-7 cells. The novel complexes are inexpensive to prepare and more effective than free drugs at low systemic toxicity.

Mass spectrometry in the study of molecular complexes between 5-fluorouracil and catechins.

5-Fluorouracil (5FU) is a widely employed antineoplastic agent that acts as antimetabolite. However, 5FU activity is strongly reduced against a subset of cancer cells called cancer stem cells (CSCs), which are believed to be responsible for chemoresistance and tumour recurrence. It was found that epigallocatechin-3-gallate (EGCG), the most abundant catechin present in green tea extract, suppresses CSCs grown in various cancers. This chemosensitizing effect of EGCG was investigated in 5FU-resistant (5FUR) CRC cells, showing that EGCG enhances 5FU-induced cytotoxicity. However, the real mechanism of an improved 5FU chemosensitivity in the presence of EGCG was not evaluated. Considering the capability of catechins to form bimolecular noncovalent complexes, in the present study, the interaction of catechins and 5FU was studied by different mass spectrometric approaches. The ESI(+) and ESI(-) spectra of [5FU-catechin] mixtures were studied, showing the formation of protonated and deprotonated bimolecular complexes, whose nature was confirmed by MS/MS experiments (product and precursor ion scans). To exclude the possible origin of these species as ESI artefacts, a further series of experiments were performed by high-resolution liquid chromatography-mass spectrometry. By this approach, bimolecular complexes have been detected at retention times different from those of free 5FU and catechins, proving their presence in the original solution. Analogous studies were performed on 5FU-green tea extract mixtures, showing that 5FU leads to complexes not only with EGCG but also with other catechins. These molecular species, differently to free 5FU drug alone, would in principle possess a new biological activity and could be an explanation of the described activity cited above.

Cell-Permeant Bioadaptors for Cytosolic Delivery of Native Antibodies: A "Mix-and-Go" Approach.

Antibodies are powerful tools that may potentially find wide applications in live-cell bioimaging, disease diagnostics, and therapeutics. Their practical applications have however remained limited thus far, owing to their inability to cross the cell membrane. Existing approaches for cytosolic delivery of functional antibodies are available, but they are constantly plagued by the need for chemical/genetic modifications, low delivery efficiency, and severe endolysosomal trapping. Consequently, it is of paramount importance to develop new strategies capable of highly efficient cytosolic delivery of native antibodies with immediate bioavailability. Herein, we report a modification-free, convenient “mix-and-go” strategy for the cytosolic delivery of native antibodies to different live mammalian cells efficiently, with minimal endolysosomal trapping and immediate bioavailability. By simply mixing a cell-permeant bioadaptor (derived from protein A or TRIM21) with a commercially available off-the-shelf antibody, the resulting noncovalent complex could be immediately used for intracellular delivery of native antibodies needed in subsequent cytosolic target engagement. The versatility of this approach was successfully illustrated in a number of applications, including antibody-based, live-cell imaging of the endogenous protein glutathionylation to detect oxidative cell stress, antibody-based activation of endogenous caspase-3, and inhibition of endogenous PTP1B activity, and finally TRIM21-mediated endogenous protein degradation for potential targeted therapy. Our results thus indicate this newly developed, “mix-and-go” antibody delivery method should have broad applications in chemical biology and future drug discovery.

LILBID laser dissociation curves: a mass spectrometry-based method for the quantitative assessment of dsDNA binding affinities

One current goal in native mass spectrometry is the assignment of binding affinities to noncovalent complexes. Here we introduce a novel implementation of the existing laser-induced liquid bead ion desorption (LILBID) mass spectrometry method: this new method, LILBID laser dissociation curves, assesses binding strengths quantitatively. In all LILBID applications, aqueous sample droplets are irradiated by 3 µm laser pulses. Variation of the laser energy transferred to the droplet during desorption affects the degree of complex dissociation. In LILBID laser dissociation curves, laser energy transfer is purposely varied, and a binding affinity is calculated from the resulting complex dissociation. A series of dsDNAs with different binding affinities was assessed using LILBID laser dissociation curves. The binding affinity results from the LILBID laser dissociation curves strongly correlated with the melting temperatures from UV melting curves and with dissociation constants from isothermal titration calorimetry, standard solution phase methods. LILBID laser dissociation curve data also showed good reproducibility and successfully predicted the melting temperatures and dissociation constants of three DNA sequences. LILBID laser dissociation curves are a promising native mass spectrometry binding affinity method, with reduced time and sample consumption compared to melting curves or titrations.

Construction and Humidity Response of a Room‐Temperature‐Phosphorescent Hybrid Xerogel Based on a Multicharge Supramolecular Assembly

Organic room‐temperature phosphorescence (RTP) has attracted tremendous attention in recent years due to its potential utility in combination with artificial soft materials. Herein, a room‐temperature‐phosphorescent hybrid xerogel held together by electrostatic and host–guest interactions is reported. The xerogel is constructed by noncovalent complexation of 7‐[6‐deoxy‐6‐(2‐sulfonic)]‐β‐cyclodextrin (SCD) with the phosphor bromophenyl‐methyl‐pyridinium chloride (PYCl) and in situ incorporation of the anionic SCD⊃PYCl complex into a cationic amino clay (AC) via electrostatic interactions. The resulting xerogel, designated AC/SCD⊃PYCl, has a network structure that can suppress vibrational and nonradiative relaxation of the phosphor, leading to green RTP emission as well as good fluorescence–phosphorescence dual emission. Notably, the intensity of the xerogel RTP varies with humidity and can be switched on and off repeatedly, which indicates that the xerogel has potential utility as an organic light‐emitting humidity‐sensing material.

Quantum Monte Carlo benchmarking of large noncovalent complexes in the L7 benchmark set.

We have used diffusion Monte Carlo (DMC) to perform calculations on the L7 benchmark set. DMC is a stochastic numerical integration scheme in real-space and part of a larger set of quantum Monte Carlo methods. The L7 set was designed to test the ability of electronic structure methods to include dispersive interactions. While the agreement between DMC and quantum-chemical state-of-the-art methods is excellent for some of the structures, there are significant differences in others. In contrast to wavefunction-based quantum chemical methods, DMC is a first-principle many-body method with the many-body wavefunction evolving in real space. It includes explicitly all electron-electron interactions and is relatively insensitive to the size of the basis set.

Intermolecular Interactions Involving Heavy Alkenes H2Si=TH2 (T = C, Si, Ge, Sn, Pb) with H2O and HCl: Tetrel Bond and Hydrogen Bond.

The intermolecular interactions between the heavy alkenes H2Si=TH2 (T = C, Si, Ge, Sn, Pb) and H2O or HCl have been explored at the CCSD(T)/aug-cc-pVTZ//MP2/aug-cc-pVDZ level. The various hydrogen bond (HB) and tetrel bond (TB) complexes can be located on the basis of molecular electrostatic potential maps of the isolated monomers. The competition between TB and HB interactions has been investigated through the relaxed potential energy surface scan. The results indicate that the HB complexes become more and more unstable relative to the TB complexes with the increase of the T atomic number, and cannot even retain as a minimum in some cases, for H2Si=TH2···H2O systems. In contrast, the HB complexes are generally more stable than TB complexes, and the TB complexes exhibit rather weak binding strength, for H2Si=TH2···HCl systems. The majority of the TB complexes formed between H2Si=TH2 and H2O possesses very strong binding strength with covalent characteristics. The noncovalent TB complexes can be divided into two types on the basis of the orbital interactions: π-hole complexes, with binding angles ranging from 91 to 111°, and hybrid σ/π-hole complexes, with binding angles ranging from 130 to 165°. The interplay between different molecular interactions has been explored, and an interesting result is that the covalent TB interaction is significantly abated and becomes noncovalent because of the competitive effect.