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Apart from chemical and allopathic drugs, several medicinal plants contain phytochemicals that are potentially useful to counter the COVID-19 pandemic. Withania somnifera (Ashwagandha), which has a good effect on some viral infections, can be considered as a candidate against the virus. In the present study, thirty-nine natural compounds of Ashwagandha were investigated in terms of their binding to the important drug targets to treat the COVID-19. Although the molecular docking calculations reveal the binding affinities of the compounds to Mpro, TMPRSS2, NSP15, PLpro, Spike RBD + ACE2, RdRp and NSP12 as targets in controlling the coronavirus enzymes, Withanoside II is expected to be the most effective compound due to the high affinity in binding with many of considered targets. Furthermore, the Withanoside III, IV, V, X, and XI have favorable binding affinities as ligands with respect to the MM/GBSA calculations. The molecular dynamics simulations MD explore a stable hydrogen bond network between ligands and the active sites residues. Also, the dynamic fluctuations of the binding site residues verify their tight binding to ligands. Moreover, the stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for all mentioned complexes. The TMPRSS2-Withanolide Q and Mpro-Withanoside IV complexes are the most stable pairs using the MM/GBSA calculations and MD simulation. Communicated by Ramaswamy H. Sarma TMPRSS2 receptor in terms of human relative proteins and Mpro and NSP15 receptors on coronavirus itself target are the effective target for inhibitory effects of Withania somnifera compounds. The highest binding affinity is related for WithanolideD, WithanolideQ, WithanosideIV, WithanosideIII, WithanosideV, WithanosideII, and 2,3-Didehydrosomnifericin ligands on the Spike RBD + ACE2, TMPRSS2, Mpro, PLpro, RdRp, NSP15, and NSP12 receptors, respectively. Withanolide compounds on human related proteins targets and Withanoside structures on coronavirus itself receptors have the highest inhibitory potential. Withanoside II ligand is expected to be the most effective compound due to the high affinity to bind to many considered targets. The stability of ligand-protein complexes is approved by the RMSD ranges lower than 0.5 Å in equilibration zone for WithanolideQ-TMPRSS2 and WithanosideIV-Mpro complexes.

Prostate-specific membrane antigen (PSMA), also called glutamate carboxypeptidase II (GCP(II)), is a Zn-dependent metalloprotease that is known as a well prostate cancer indication and a potential targeting towards anti-cancer medicines and drug delivery. Because of its centrality in the diagnostics and treatment of prostate cancer, several types of inhibitors are designed with particular scaffolds. In this study, important groups of related inhibitors as well as reported experimental and computational studies are being reviewed, in which we examined three functional groups on each group of structures. The importance of computational biochemistry and the necessity of extensive research in this area on PSMA and its effective ligands are recommended.

In the present study, the tautomeric process, intramolecular hydrogen bonding (IMHB), and π-electron delocalization (π-ED) of 2-selenoformyl-3-thioxo-propionaldehyde (STP) in the first singlet and triplet excited states were investigated by CIS and TD-DFT methods. The relative energies of hydrogen-bonded tautomers in both excited states indicate that the thiol/enol conformers are the most/least stable forms. In this regard, a detailed analysis of various tautomeric equilibriums, different types of hydrogen bonds, and π-electron delocalization was performed. The electronic energies of different tautomers indicate the thermodynamic preference of thiol with respect to the other forms. Furthermore, the low activation energy barriers of thione⇄thiol equilibrium also show the kinetic preference of thiol. On the other hand, the estimation of different hydrogen bond energies emphasizes the stronger IMHB of enol. Moreover, the evaluation of π-ED by the structural parameter of Gilli (λ) represents the significance of electron mobility in the enol conformers. Consequently, the duality between the IMHB and π-ED with the thermodynamic stability order of tautomers indicates that the tautomeric phenomenons play a dominant role in determining the stability of the benchmark structures in both singlet and triplet excited states.

In the present study, a couple of simple models were presented to estimate the energy of individual hydrogen bonds in traditional base pairs. In this regard, formamide and formamidine dimers and a set of their derivatives with different functional groups such as F, Cl, Br, CH3, CN, ethynyl, nitroso, and vinyl were considered. All of these structures are optimized by M06-2X and MP2 methods in conjunctions with 6-311 + + G(d,p) basis set. The computational results showed that the hydrogen bond energy in the first method is higher than the MP2 and also the NHN interactions are stronger than the corresponding NHO ones. Moreover, the relationships between the energy hydrogen bonds and all of the geometrical, topological, and molecular orbitals descriptors were also explored. The absolute values of the correlation coefficient (R2) indicated the best linear relationships between the electron density at the hydrogen bond critical point (ρ(r)) and the energy of NHN (R2 = 0.98) and NHO (R2 = 0.82) hydrogen bonds. Based on these equations, it was found that the orders of calculated individual HB energies of the Watson-Crick base pairs are completely similar to the compliance constant model of Gruenberg. Finally, the energy of individual bonds in a set of usual base pairs was evaluated and compared with their complexation energies. The slight difference between ƩEHB and ΔEComp reflects the high accuracy of the proposed models and equations.

In the present work, a detailed investigation of synergistic effects between the intramolecular hydrogen bond (IMHB) and π-electron delocalization (π-ED) of 3-hydroxy prop-2-en thial (HPT) and its halogenated derivatives was performed. For this purpose, at first, the π-ED in the enol form of the benchmark systems by various aromaticity indices such as λ, λ, HOMA, NICS, PDI, ATI, and FLUπ were evaluated. On the other hand, the strength of IMHB by various descriptors such as energetical, geometrical, spectral, topological, and molecular orbital parameters was also estimated. For better understanding the nature of the synergistic phenomenon, we examined and compared the linear relationships between the π-ED indices with the HB descriptors. Our results show that the geometrical indicators have the best linear relationships with all of the mentioned HB parameters. Also, according to their absolute linear correlation coefficients, the following order is concluded: λ > λ > HOMA > FLUπ > ATI > NICS (1) > PDI > NICS (0)Finally, the synergistic effect between the π-ED and IMHB from the position and nature point of views is discussed. These results clearly show that the synergistic effect of R1 derivatives is negative, while the corresponding effects of R2 and R3 ones are positive. Moreover, the synergetic effects also depend on the nature of substitutions especially their electronegativity values (F > Br > Cl).

Previously, we have proposed a computational model for decision-making in crisis situations called C-RPD (Computational Recognition Primed Decision). In this paper, a software development process customized for Crisis Situations Decision-Making Systems (CSDMSs) is proposed. Agile processes can skillfully manage uncertainty in software requirements and some of their features like incremental development can solve some problems in developing CSDMSs. However, these processes do not provide comprehensive solutions for issues like the lack of enough knowledge about CSDMSs, very rapid changes, urgent need to overcome security challenges, high development unpredictability, and the performance test. Extreme Programming (XP) is one of the best and most widely-used agile processes. In this article, a customized version of XP called Crisis Situations Decision-Making Systems Software Development Process (CSDP) is proposed. Standing first and second in five national and international RoboCup rescue agent simulation tournaments from 2006 to 2010 bear witness to the efficiency of the developed software using CSDP. Relying on its characteristics, CSDP has been able to practically tackle the challenges of developing CSDMSs such as the lack of crisis-related knowledge and cumulative nature of crisis-related knowledge, difficulty of extracting knowledge, long development cycle, and sudden and frequent changes in system requirements.

A denial‐of‐service (DoS) attack is a serious attack that targets web applications. According to Imperva, DoS attacks in the application layer comprise 60% of all the DoS attacks. Nowadays, attacks have grown into application‐ and business‐layer attacks, and vulnerability‐analysis tools are unable to detect business‐layer vulnerabilities (logic‐related vulnerabilities). This paper presents the business‐layer dynamic application security tester (BLDAST) as a dynamic, black‐box vulnerability‐analysis approach to identify the business‐logic vulnerabilities of a web application against DoS attacks. BLDAST evaluates the resiliency of web applications by detecting vulnerable business processes. The evaluation of six widely used web applications shows that BLDAST can detect the vulnerabilities with 100% accuracy. BLDAST detected 30 vulnerabilities in the selected web applications; more than half of the detected vulnerabilities were new and unknown. Furthermore, the precision of BLDAST for detecting the business processes is shown to be 94%, while the generated user navigation graph is improved by 62.8% because of the detection of similar web pages.

In the present work, a comprehensive theoretical study of diformyl (DFA) and dithioformylamine (DTFA) were performed by various theoretical methods, HF, B3LYP, and MP2 with 6‑311++G(3df,3pd) basis set, and the equilibrium conformations were determined. According to these calculations, tautomeric and conformeric preferences, intramolecular hydrogen bond (IMHB) and π-electron delocalization were investigated. Generally, DAI/DTAI tautomers have extra stability with respect to the AI/TAI ones. Also, among the AI/TAI series, the AI-11/TAI-13 conformer with/without IMHB is the most stable tautomer. Moreover, our computation results reveal that the formation of the intramolecular hydrogen bond is accepted as the origin of conformational preferences. The results of hydrogen bond descriptors, such as HB energy, geometrical, topological, spectroscopic and molecular orbital parameters are in agreement with the related energy values and show that the strength of intramolecular hydrogen bond in DFA is more than DTFA ones. On the other hands, π-electron delocalization of chelated rings was measured using various indices, such as q, λ', λ, and HOMA index. Finally, the orders of hydrogen bond strength and π-electron delocalization, obtained by some of the indices, support the resonance assisted hydrogen bond theory.

Ab initio calculations have been performed to study the complexes between the noble gas elements (Ae = Ne, Ar, Kr) with a series of benzene isoelectronic heterocyclic compounds of benzene, including boraphosphinine (BP), borazine (BN), and alumazine (AlN), at MP2/Aug-CC-pVTZ level of theory. According to the molecular electrostatic potential (MEP) iso-surface of BP, BN, and AlN, the active sites of rings are identified which utilized to predict the relative strength of aerogen···π (Ae···π) interactions as follows: Kr···π > Ar···π > Ne···π/Ae···BP > Ae···BN > Ae···AlN. Then, the equilibrium structures of all the complexes are characterized, and their energetic, geometrical, topological, and molecular orbital descriptors were used to estimate the strength of Ae···π interactions, that are in line with MEP results. Energy decomposition analysis reveals that dispersion effects play a vital role in formation of the Ae···π complexes. Furthermore, intermolecular interactions were also investigated with the quantum theory of atoms in molecules (QTAIM) and the non-covalent interactions (NCI) and natural bond orbital’s (NBO) analysis. NBO analysis showed that like the benzene complexes, charge transfers from the noble gas atom to heterocyclic ring have occurred. Finally, the aromaticity of the rings is measured using the well-established indices namely the nucleus independent chemical shift (NICS) and the average two-center index (ATI).

In the current research, the performance of molecular tailoring approach (MTA) for estimation of the intramolecular hydrogen bond (IMHB) energies of the simple resonance-assisted hydrogen bond (RAHB) systems was theoretically investigated. First, a wide range of malonaldehyde derivatives (36 members) including the F, Cl, Br, CN, NO2, ethen (-CH=CH2), ethin (-C ≡ CH), CF3, OCH3, C2H5, CH3, and Ph substitutions at R1, R2, and R3 positions were considered. Then, all of these molecules at MP2/6-311++G(d, p) level of theory have been optimized and their MTA energies were calculated. Furthermore, various qualitative descriptors of IMHB such as structural, spectroscopic, topological, and molecular orbital parameters were considered, and all of correlations between these factors and MTA energies were explored. According to their regression coefficients (R2), the linear characteristic of correlations obeys the following order:$$ {H}_{\mathrm{H}\dots \mathrm{O}}>{d}_{\mathrm{O}-\mathrm{H}}>{E}_{\mathrm{CT}}>{V}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{\rho}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{\nu}_{\mathrm{O}-\mathrm{H}}>{d}_{\mathrm{H}\bullet \bullet \bullet \mathrm{O}}>{d}_{\mathrm{O}\bullet \bullet \bullet \mathrm{O}} $$$$ 0.952\kern1.5em 0.940\kern1.2em 0.936\kern0.75em 0.914\kern1.2em 0.901\kern1.2em 0.834\kern1em 0.789\kern1.3em 0.755 $$ These correlation coefficients have compared with the corresponding R2 values of other models such as RRM, RBM, GCM, IRM, and OCM, which leads to the following order of linearity:$$ \mathrm{MTA}\ge \mathrm{RRM}>\mathrm{RBM}>\mathrm{GCM}>\mathrm{IRM}>\mathrm{OCM}. $$ Finally, the significance of π-electron delocalization (π-ED) of RAHB rings is also evaluated by the geometrical factor of Gilli (λ) and the harmonic oscillator model of aromaticity (HOMA) that presents the excellent linear correlations with MTA energies, which may be implied on the validity of RAHB theory.

Among physiologically active compounds isolated from marine organisms, the pyrroloquinoline alkaloids (PQAs) family consisting of damirone A/C, batzelline A/D, makaluvamine O and makaluvone exhibit numerous biological activities derived from the inimitable highly-fused structures. Their structural and electronic properties were investigated through intramolecular interactions, electron affinities (EA), reduction potentials (E°) and complexation of compounds with magnesium and guanidinium cations (ionic and hydrogen bond interactions) using quantum mechanical calculations in the gas phase and solution. For both series of complexes, the most and least stable ones correspond to damirone A and batzelline D, respectively. The energy data, geometrical parameters, and the minima of electrostatic potentials (Vmin) are in good correlation with the results of population analyses. The localized molecular orbital energy decomposition analyses (LMO-EDA) demonstrate that the electrostatic interaction is the most important stabilizing component. The EA values are positive in the gas phase and solution, and are evaluated with the increase in the dielectric constant of solvent. Increase in the EA values and decrease in the E° values are observed after complexation with guanidinium and magnesium cations. Those changes are higher for electron-rich compounds compared to electron-deficient ones, containing halogen substituents.

Quantum chemical study of the nature of interactions between the boraphosphinine (BP) and alumaphosphinine (AlP) with some of the alkali metal cations (Li+, Na+, K+) and alkaline-earth cations (Be2+, Mg2+, Ca2+) have been investigated at M06-2X/6-311++G(d,p) level of theory. At first, the molecular and electronic structures of the rings (R) and cations (M) were completely analyzed. According to the molecular electrostatic potential (MEP) iso-surface of BP and AlP, the active sites of rings are identified and also predict the relative strength of M···R interactions as follows: Be2+···R > Mg2+···R > Ca2+···R > Li+···R > Na+···R > K+···R. Furthermore, all of the complexes are characterized and their energetic components, geometrical, topological, and molecular orbital descriptors were used to estimate the strength of M···R interactions. The result shows that the non-covalent interactions of M···AlP are significantly stronger than the corresponding M···BP ones. Detail investigation of M···BP and M···AlP series clearly shows a substantial difference in the nature of interactions, cation–π/cation–lone pair (LP) in M···BP/M···AlP complexes. The excellent linear correlations between the energy terms and all of the mentioned descriptors are obtained. Finally, two well-established indices namely the nucleus independent chemical shift (NICS) and the average two-center index (ATI) were used to evaluate the aromaticity of the studied rings before and after complexation.

In the present work, the hydrogen bond (HB) interactions between substituted syn and anti rotamers of methyl N-(2-pyridyl) carbamate and acetic acid were investigated using quantum mechanical (QM) calculations. The rotamers have two typical active sites to form hydrogen bonds with acetic acid, such that four stable complexes are found on the potential energy surface. The complexes in which the oxygen atom of carbamate acts as proton acceptor are stabilized by EWSs and are destabilized by EDSs. The trend in the effects of substituents is reversed in the other two complexes, in which the nitrogen atom of ring is involved in the interaction. According to energy data, the substituent effects on the interaction energy can be expressed by Hammett constants. The natural resonance theory (NRT) model was used to investigate the charge distribution on the carbamate group and to discuss the interaction energies. The individual HB energies were estimated to evaluate their cooperative contributions on the interaction energies of the complexes. In addition, the localized molecular orbital energy decomposition analyses (LMO-EDA) demonstrate that the electrostatic interactions are the most important stabilizing components of interactions.

Many organizations today use a variety of security and monitoring tools at various levels of defense. These tools often generate heterogeneous alerts and logs when an attack occurs. Because of the large volume and dispersion of these alerts and logs, the manual cross-correlation of them is a time-consuming and labor-intensive task. The main challenge is that heterogeneous alerts and logs generated as a result of an attack stage do not necessarily have common features, or there are no explicit relationships between them that can be used for cross-correlation. In this paper, we overcome this deficiency by presenting HAL-RD, a novel technique that uses resource dependencies to cross-correlate heterogeneous alerts and logs. In this technique, we track logs for backward and forward dependencies between resources. This information is then used to construct an attack state graph, which is a directed graph whose nodes represent attack states and whose directed edges represent the chronological ordering between them. Each attack state integrates information found in multiple heterogeneous alerts, logs, and OS-level operations, which relate to one stage in a multi-stage attack. In certain circumstances, the attack state graph is incrementally updated. By doing this, when an attacker continues his/her multi-stage attack after a delay, all of his/her activities are identified. The evaluation results demonstrate the effectiveness of HAL-RD for cross-correlating heterogeneous alerts and logs.

The Dendritic Cell Algorithm (DCA) as one of the emerging evolutionary algorithms is based on the behavior of the specific immune agents; known as Dendritic Cells (DCs). DCA has several potentially beneficial features for binary classification problems. In this paper, we aim at providing a new version of this immune-inspired mechanism acts as a semi-supervised classifier which can be a defensive shield in network intrusion detection problem. Till now, no strategy or idea has already been adopted on the GetAntigen() function on detection phase, but randomly sampling entails the DCA to provide undesirable results in several cycles in each time. This leads to uncertainty. Whereas it must be accomplished by biological behaviors of DCs in tissues, we have proposed a novel strategy which exactly acts based on its immunological functionalities of dendritic cells. The proposed mechanism focuses on two items: First, to obviate the challenge of needing to have a preordered antigen set for computing danger signal, and the second, to provide a novel immune-inspired idea in order to non-random data sampling. A variable functional migration threshold is also computed cycle by cycle that shows necessity of the Migration threshold (MT) flexibility. A significant criterion so called capability of intrusion detection (CID) used for tests. All of the tests have been performed in a new benchmark dataset named UNSW-NB15. Experimental consequences demonstrate that the present schema dominates the standard DCA and has higher CID in comparison with other approaches found in literature., Comment: 24 pages, 7 figures

In the present study, solvent effects on the molecular stability, intramolecular hydrogen bond (IMHB), and π-electron delocalization (π-ED) in some of the simple resonance-assisted hydrogen bond (RAHB) systems with different donors and acceptors are investigated. In this regard, all of the H-bonded structures (enol, thiol, and selenol) in the gas phase and presence of water/DMSO solvents with polarizable continuum (PCM)/self-consistent isodensity PCM methods at the M06-2X/6-311G++(d,p) level of theory are optimized. Relative energies clearly indicate that the enol conformers are more stable than the thiol and selenol ones in the gas phase while in the presence of polar solvents, the thiol structures are more stable than the other members. In the RAHB systems, the IMHB, π-ED, and tautomerization process are important factors in determining the stability of the H-bonded conformers. A survey of tautomeric equilibriums clearly shows that the tautomerization/activation energy of thio ⇋ thiol equilibrium is greater/smaller than the other equilibriums. These results reveal that the thiol tautomer is more preferred than the enol and selenol ones, from kinetic and thermodynamic points of view. Estimation of the IMHB by different descriptors emphasizes the presence of a stronger IMHB in the enol conformers. Moreover, the π-ED of enol tautomers are greater than those of the thiol and selenol ones. The results of IMHB and π-ED descriptors are compatible/incompatible with the stability order of the gas phase/solvents. Consequently, one can conclude that in the gas phase, the IMHB and π-ED are superior factors to determine the stability of tautomers. But in the presence of polar solvents, the tautomerization process is a dominant factor.

A sustained drug delivery system is developed by using nonionic polymer to formulate drug release rate from silica based capsules. To serve this purpose, silica based capsules filled with poly(ethylene glycol) (PEG) were incorporated with a veterinary antibiotic drug enrofloxacin (EFX); as a model hydrophobic drug by using a general and facile sol-gel route. The physicochemical properties of the prepared drug-loaded composites were investigated by scanning electron microscope (SEM), nitrogen adsorption, Fourier transform infrared spectroscopy and thermal analysis (TGA). The impact of the media's ionic strength on the drug release was evaluated over a range of 0–0.4 M to simulate the gastrointestinal feed in two physiological pH conditions. Sodium chloride was applied for ionic concentration adjustment due to its ability to salt out polymers in the midrange of the lyotropic series. Simultaneously, the drug release kinetics was evaluated by fitting experimental data to common empirical (zero-order, first order and Higuchi) and semi-empirical (Ritger-Peppas and Sahlin-Peppas) models. The drug release kinetics from capsules revealed a non-Fickian diffusion and pure relaxation-controlled release. Of these models, Sahlin-Peppas equation best fit the release data of EFX. To determine the best model, non-linear regressions were carried out. Furthermore, we compare a computational model to experimental data for drug-polymer and drug-SiO2 interactions at B3LYP/6-31 + G(d) level of theory. This model has been suggested based on the active sites of its component, which are characterized by MEP. Finally, the HOMO-LUMO and vibrational analysis were performed.

In the present study, the conformational analysis, intramolecular hydrogen bond, π-electron delocalization, and tautomeric equilibriums in 2-selenoformyl-3-thioxo-propionaldehyde (STP) were investigated. First, conformational analysis of STP was performed, and our results have shown that the chelated thiol structures are more stable than the chelated enol and selenol ones; HB Thiol < HB Enol < HB Selenol. To justify this order, the affective factors on this stability such as tautomerism, hydrogen bonding, and π-electron delocalization were comprehensively investigated. Survey of tautomeric equilibriums in STP indicates that destabilization energy of keto⇋enol equilibrium (about 50 kJ/mol) is more than the seleno⇋selenol (about 22 kJ/mol) and then thio⇋thiol (about 20 kJ/mol) cases. Description of different hydrogen bonds by energetic, geometrical, topological, and molecular orbitals emphasizes on the presence of a stronger intramolecular hydrogen bond (IMHB) in the enol forms. Furthermore, evaluation of π-electron delocalization (π-ED) represents approximate superiority of enol conformers. The achieved results by HB and π-ED analyzes are in contrast with the mentioned stability order. Ultimately, investigation of above factors indicates that the tautomerism phenomenon plays a dominant role in determining of the conformational preferences.

The electronic structure and properties of the armchair boron nitride nanotubes (BNNTs) interacted with the 5-FU drug, as an anticancer drug, are studied at the B3LYP/6-31G(d,p) level of theory. D3-Corrections were carried out for the treatment of intermolecular interactions in the hybrid complexes and encapsulated nanotubes, exactly. Results have shown that the encapsulation and adsorption of 5-FU molecule on the studied BNNTs surface are favorable processes, with a few exceptions. Also, it is found that the encapsulated nanotubes are stable than the hybrid complexes. Furthermore, we estimated the strengths of the intermolecular bonds of the benchmark systems by energetic, geometric, topological and molecular orbital descriptors. Some analyses have been made to explore any changes in the binding characteristics of the drug molecule after its attachment to the nanotubes. According to the NBO results, the charge transfer phenomenon is observed from the bonding or nonbonding orbitals of drug to the antibonding orbitals of BNNTs. Moreover, HOMO–LUMO analysis indicated that, after the adsorption process, the HOMO value slightly increased, while the LUMO value in these systems significantly reduced in the both of Drug@BNNTs groups. So, the energy gaps between HOMO and LUMO (Eg) are reduced, which emphasis on the greater intermolecular bond strength. Finally, the stability and reactivity of the Drug@BNNTs complexes have been examined from the magnitudes of the chemical reactivity descriptors such as chemical potential, global hardness, and electrophilicity index. As a consequence, BNNTs can be considered as a drug delivery vehicle for the transportation of 5-FU as anticancer drug within the biological systems.

The theory of resonance-inhibited hydrogen bonding (RIHB) is tested on some illustrative examples with enol-imine tautomerism. In contrast to the resonance-assisted hydrogen bonding (RAHB), theoretical descriptors show that here, π-resonance weakens the intramolecular hydrogen bond (IMHB) strength in the given structures. The results show that it is possible to tune the strength of RIHB by substitution in a suitable position in the molecule. Once a substituent hiders the original resonance in the RIHB system, it leads to reinforcement of IMHB and vice versa. These effects mostly are enhanced with increasing the magnitude of Hammet resonance constants. Interestingly, the IMHB becomes 0.08 A shorter, and thus quite stronger by using a powerful π-electron donating group like –O− on the basis of the RIHB theory. In general, RIHB and RAHB complement each other well, and provide a very good insight into the interplay between the resonance and hydrogen bonds.

In the current research, the origin of conformational preferences in trifluoro-acetylacetaldehyde (TFAAD) by detail analysis of the intramolecular hydrogen bond (IMHB) and π-electron delocalization (π-ED) was investigated. In this regard, all of the possible conformations of keto and enol tautomers of TFAAD at various theoretical levels were optimized. Our results reveal that the chelated enol forms (E11, E21) have extra stability with respect to the other conformations, and at all of the computational levels E21 is more stable than the E11 and identifies as the global minimum. We expected that the extra stability of E21 is probably related to the stronger intramolecular hydrogen bond (IMHB), but quantum chemical calculations confirm the stronger IMHB of E11. Since, the chelated forms are resonance assisted hydrogen bond (RAHB) systems, it seems that the π-ED concept can probably justify this duality. The significance of π-ED by the geometrical factor of Gilli (λ) and the harmonic oscillator model of aromaticity (HOMA) were assessed. According to these indicators, E21 has higher π-ED than E11, in excellent agreement with their stability order. Finally, the population analysis by the natural bond orbital method and atoms in molecules theory were carried out. The stabilization charge transfer energies of RAHB systems also indicate more π- ED in E21. Consequently the π-electron delocalization effect is the superior factor determining the global minimum. The IMHB of the chelated forms, in the first singlet excited state, were also studied. Surprisingly, the results show that the IMHB in E21 is stronger than in E11, in contrast to the ground state.

The trapping of methylglyoxal (MGO) by flavonoid aglycones has been studied using the quantum mechanical calculations at the M06-2X/6-31g (d,p) level of theory. The process can be initiated by MGO transfer on the top of flavonoid aglycone and is sequentially continued by proton transfer from hydronium ion to flavonoid aglycone, MGO and finally a H 2 O molecule. With respect to the proposed mechanism, the selected flavonoid aglycones allow us to investigate the effects of some structural properties, especially the effects of hydroxyl substituents, on the MGO trapping efficacy using the energetics and results of population analysis. The nearest carbon atoms to the hydroxyl carrier carbon of ring A (C6 and C8) are suitable positions for MGO trapping; the results show that the C8 position is more active than C6 in this process. The MGO trapping efficacy strongly depends on the number of hydroxyl groups of the ring A. The energy barrier decreases with the increase in the number of intermolecular hydrogen bonds and proton transfer between the rings A and C. Although the substituents located on various rings have role on the MGO scavenging activity of flavonoid aglycones, the effects of substituents located at the rings A and C are higher than those located at B.

Some biological activities of quinones can be attributed to the H-bonding ability of acceptor oxygen atoms. According to the results obtained from the quantum mechanical calculations performed on a wide variety of complexes between the 1,4-benzoquinone (BQ) derivatives and HF molecules, the interplay between H-bonds and individual H-bond interaction energies (EHB) can be affected by the substituents placed on the six-membered ring of BQ. The total binding energies of complexes become more negative by the electron donating substituents (EDSs) while the changes are reversed by the electron withdrawing substituents (EWSs). The mutual interplay between the X-BQ⋯(HF)n (n=1-3) interactions has been investigated using the geometrical parameters, synergetic energies (SE) and the EHB values. Hydrogen bonding decreases the reduction potentials (E0red) and increases the electron affinities (EA) of X-BQ derivatives. Linear relationships have been observed between the E0red (and EA) values and the Hammett constants of substituents.

A comprehensive theoretical investigation of the mutual effects of the cation-π, anion-π, and intramolecular hydrogen bond (IMHB) interactions in the various ternary complexes of 1,3,5-triamino-2,4,6-trinitrobenzene (ANB) with anions (A: F˗, Cl˗, Br˗) and cations (M: Li+, Na+, K+, Mg2+, Ca2+) were carried out. The energetic, geometrical, topological, and molecular orbital descriptors are employed to estimate the strength of the mentioned non-covalent interactions and their results were compared with the corresponding data of the ANB⋯M, ANB⋯A and A⋯Bz⋯M complexes, as a set of reference points. The results indicate that the presence of resonance-assisted hydrogen bond (RAHB) units decreases the strength of cation-π interaction while for anion-π interactions, the reverse process is observed. On the other hand, the RAHB units reduce the binding energies of the ternary complexes and cooperative effects between the cation-π and anion-π interactions, with respect to the A⋯Bz⋯M complexes. Furthermore, the coexistence of cation-π and anion-π interactions modulates their effects on the strength of IMHB. Finally, the harmonic oscillator model of aromaticity (HOMA) indicator was applied to analyze the influences of the mentioned interactions on the significance of the π-electron delocalization (π-ED) of the RAHB units and aromaticity of the benzene ring. It was found that the coexistence of cation-π and anion-π interactions effectively change the π˗ED and aromaticity.

In this research work, various hydrogen-bonded complexes of 5-fluorouracil (FU), as a simplest organic anticancer drug, with the adenine and guanine purine bases were investigated. First, the molecular electrostatic potentials (MEP) of all monomers (FU, A, and G) are explored and their active sites for hydrogen-bonded interactions identified. Then, the selected plausible coplanar complexes were optimized and their complexation energies obtained. Our results reveal that the FU-G complexes are more stable than the FU-A ones. Also, the most stable structures of both series were recognized, which is consistent with the MEP results of monomers. Additionally, we estimated the strengths of the individual hydrogen bonds of the benchmark systems by energetic, geometric, spectroscopic, topological, and molecular orbital descriptors. The acceptable linear correlations between the complexation energies and some of the mentioned descriptors are observed. Finally, several aromatic indices (HOMA, ATI, NICS (0), and NICS (1)) were applied to evaluate the significant of π-electron delocalization (π-ED) of 5/6 membered rings. These results show that the π-ED of the benchmark systems increases with the formation or strengthening of the HB, which is in line with the resonance-assisted hydrogen bond theory.

For the first time, the mutual influences of the intramolecular hydrogen bond (IMHB) and cation–π interactions in various complexes of salicylaldehyde, thiosalicylaldehyde and selenosalicylaldehyde...

A comprehensive theoretical study of mutual interactions between the resonance-assisted hydrogen bond (RAHB) units and benzene rings in salicylaldehyde and ortho-aminobenzaldehyde with their thio and seleno analogues, at the M062X/6-11++G(d,p) level of theory, was carried out. First, we evaluated the intramolecular hydrogen bond (IMHB) strength of the mentioned compounds by various descriptors, such as geometrical, spectroscopic, topological, molecular orbital, and energetic parameters, and then compared with the corresponding results of malonaldehyde and β-aminoacrolein with their thio and seleno analogues. According to the theoretical results, it was found that the merging of benzene rings and RAHB units reduced the strength of the IMHB in all of the benchmark systems. The magnitude of these reductions in the O-H⋯Y systems is greater than that of the N-H⋯Y ones. Also, the substitution of S and Se atoms instead of O increased the IMHB strength and obeyed the following order; X-H⋯Se > X-H⋯S > X-H⋯O. Second, a set of aromaticity indices such as the harmonic oscillator model of aromaticity (HOMA), the nucleus-independent chemical shift (NICS), the para delocalization index (PDI), and the average two-center index (ATI) were applied to evaluate the significance of the aromaticity of benzene rings and π-ED of RAHB units in the studied molecules. The comparison between these results and the respective amounts of the benzene ring, malonaldehyde, and β-aminoacrolein analogues reveals that the coupling of benzene and RAHB rings decreased the π-ED and aromaticity in both of them. These reductions approximately increase with the replacement of O by N in the proton donor group. Finally, the results show that the π-ED of RAHB units increases with substitution of O by S and Se, while for the aromaticity of the benzene rings the reverse process is observed. The majority increment in the π-ED of RAHB units and also a reduction in the aromaticity of the benzene rings are related to an X-H⋯Se system that is followed by X-H⋯S and X-H⋯O systems.

O, S, Se, and P atoms are considered as different proton donor/acceptor moieties in the resonance-inhibited hydrogen bonded (RIHB) interactions to conduct a comparative investigation. In order to study the effects of resonance and σ-skeleton planarity, the corresponding saturated and planar molecules are also computed. Moreover, to provide a broader perspective, all the given systems are compared to their resonance-assisted hydrogen bonded (RAHB) analogues. The natural bond orbital (NBO), the quantum theory of atoms in molecule (QTAIM), and the gauge-independent atomic orbital (GIAO) analyses, are performed to estimate the strength and nature of the intramolecular hydrogen bonds (IMHBs). The strength of IMHBs is also estimated using energy differences between closed and open conformers. According to the results, all the given RIHB systems suggest that resonance can obviously decrease the strength of the IMHBs. However, in the RIHB systems and also in some RAHB ones, the role of π-conjugation in the IMHB formation is less important than that of σ-planarity. In other words, the constraints imposed by σ-skeleton cause both the H-bond acceptor and donor groups to be situated close to each other; these effects outweigh the undesirable results of resonance, which totally lead to the formation of the RIHB.

Artificial immune system (AIS) as a good prototype for developing Machine Learning (ML) is a promising candidate to design Intrusion Detection System (IDS). Two of its prevalent paradigms, the negative selection, and the danger theory, inspired by immunity responses of the powerful human immune system (HIS) are being widely used in this case. In this paper, we proposed a novel sophisticated hybrid method including two defensive lines by using two aforesaid mechanisms. In the proposed method, decentralized cooperation of dendritic cells together with mature detectors acts as a stimulator to generate efficient and accurate detectors and retain memory in the long-term that meant security control via ensuring immunity. Simulating such a system was applicable only by establishing artificial life cycles in the MATLAB environment. Experimental consequences demonstrate that the present schema gradually ameliorates its overall performance during the incipient stages of life cycles and also it is more capable than the previous ones found in the literature.

A comprehensive theoretical study of the mutual effects of the aerogen bond and cation-π interactions in the several ternary complexes of heterocyclic rings with noble gas elements (Ar, Kr) and cat...

According to the resonance assisted hydrogen bond (RAHB) theory, the π-electron delocalization (π-ED) promotes the intramolecular hydrogen bond (IMHB). Since the relation between the IMHB and π-ED are not well known, in the present work, the linear correlations between the descriptors of π-ED and estimated IMHB energies were systematically investigated. In this regard, the significance of π-ED in chelated forms of the benchmark systems by various descriptors, such as λ, λ′, HOMA, NICS, PDI, ATI, FLU and FLUπ were evaluated. On the other hand, the IMHB energy of RAHB units by some adopted models, such as RRM, RBM, GCM, IRM and OCM are estimated. Furthermore, we explored all of the possible linear correlations between the π-ED indices and various IMHB energies to judge about the performance of RAHB theory. According to our results, it was found that there are great liner correlations between the RRM, RBM and GCM than IRM and OCM methods with some of the π-electron delocalization indices; RRM: λ′ > FLU > λ > HOMA > FLUπ ≈ ATI > PDI > NICS(1) > NICS(0) RBM: λ′ > λ > HOMA > FLU > FLUπ > ATI > PDI > NICS(1) > NICS(0) GCM: λ′ ≈ HOMA > λ > PDI > FLU > FLUπ > NICS(1) > ATI > NICS(0). Surprisingly, the bond order factor of Gilli (λ′), which introduced similar to λ, has the best linear relationship with the IMHB energies. Consequently, the linear coefficients between the RRM, RBM and GCM energies with HOMA, λ and λ′ descriptors are in agreement with the RAHB theory.

The interaction of a single-walled carbon nanotube (SWCNT) with the Cp 2 Zr + -CH 3 has been studied with a hybrid quantum mechanics/molecular mechanics (QM/MM) method and density functional theory. At the first step, the QM/MM method has been validated by comparing its results with those of a related full QM approach. In this step, we used benzene, isobutane, and carboxyl species to model π⋯π, CH⋯π, and covalent interactions, respectively. According to our results, the QM/MM method is accurate enough to investigate covalent and noncovalent interactions with the surface of CNTs. After validating the method, the possible complex, i.e. Metallocene-CNT, structures have been investigated. We considered different π⋯π and CH⋯π configurations and found that: The Cp 2 Zr + -CH 3 can be attached to SWCNT via both π⋯π and C-H⋯π noncovalent interactions. The C-H⋯π configurations are more stable than the π⋯π analogues and those with the zirconium atom near the CNT surface are the most stable ones. We also examined the influence of the CNT on the electronic and steric properties of the metallocene. While the tube has a small effect on the electronic properties of the catalyst, it has a considerable impact on its steric environment, which may lead to the high molecular weight and tacticity products.

We first use the second-order Moller–Plesset theory to optimize β-aminoacrolein, β-thioaminoacrolein and a set of their halogenated derivatives, which involve N–H···O and N–H···S hydrogen bonds. Then, four different methods, namely rotation barrier method (RBM), isodesmic reaction method (IRM), geometry corrected method (GCM) and related rotamers method, (RRM) are utilized to estimate the intramolecular hydrogen bond (IMHB) energies. The linear correlations between the estimated IMHB energies and some hydrogen bond strength descriptors such as geometrical, electron density topological and spectroscopic parameters are obtained. According to our data, RRM and RBM have the best linear correlations with all of the hydrogen bond descriptors, while GCM and IRM do not reveal suitable results. It is assumed that the performance or reliability of the estimating methods is determined based on the value of squared regression coefficients (R 2). By adding the results of the previous studies including OH···O, OH···S and NH···O hydrogen bond units to the present obtained data, the methods can be sorted according to their relative reliability as follows: RRM > RBM ≫ GCM > IRM.

In the present study, for the first time, the first singlet excited state (S1) intramolecular hydrogen bond (IMHB) of malonaldehyde derivatives by time-dependent density functional theory (TD-DFT) and configuration interaction singles (CIS) with 6–311++G(d, p) basis set is investigated. In this regard, we initially characterized the equilibrium structures of the first singlet excited states of the benchmark systems and some of their properties such as excitation energies, oscillator strengths and dipole moments were analyzed. Then, the IMHB energies have been calculated by several adopted methods, such as potential energy density (PED) of Espinosa, related rotamers method (RRM) and rotational barrier method (RBM). The RBM and RRM energies appear grossly overestimate the intramolecular hydrogen bond energies as compared to the PED method and are not convenient for estimation the IMHB energy of excited states. Then, the more reliable PED results were used to systematically investigate the halogen substitution effects. It was found that the halogen replacement at R3 position decreases the IMHB energies, both in the ground and the first singlet excited states, while the halogen substitution at R1 and R2 positions of ground and excited states have paradoxical effects on the IMHB energies. Subsequently, the geometrical, topological, molecular orbital and spectroscopic descriptors of IMHB are comprehensively examined and various correlations between the PED energies and different HB descriptors are explored. Our results show that the excellent linear correlations between the PED energies and the majority of HB descriptors exist. Interestingly, the linear character of correlations between the HB descriptors with CIS energies is more than the TD-DFT ones. Consequently, on the basis of these correlations, one can claim that the PED method, E PED ≈ V(r BCP)/2, is a trusty equation for estimation of IMHB energy of RAHB systems, both in the ground and first singlet excited states (S1).

Web application vulnerability scanners cannot detect business logic vulnerabilities (vulnerabilities related to logic) because they are not able to understand business logic of the web application. In order to identify business logic of the web application, this paper presents BLProM, the black box approach that identifies business processes of the web application. Detecting business processes of the web applications can be used in dynamic security testing to determine business logic vulnerabilities in the web applications. BLProM first extracts navigation graph of the web application then identifies business processes from the navigation graph. The evaluation conducted on three well-known open source web applications shows that BLProM is able to detect business logic processes. Experimental results show that BLProM improves web application scanning because it clusters web application pages and prevent scanning similar pages. The proposed approach is compared to OWASP ZAP, an open source web scanner. We show that BLProM improves web application scanning about % 96.

In the present study, various hydrogen bonded complexes between five-fluorouracil (FU) with AT and GC base pairs were studied. First, to determine the affinity of different sites of the parent structures (FU, AT, and GC) for the hydrogen bond formation, their molecular electrostatic potentials are explored. The complexation energies and the strength of individual HBs of the plausible complexes were evaluated by energetic, geometric, spectroscopic, topologic, and molecular orbital descriptors. Our results reveal that, the FU-GC complexes (34.76-44.42 kcal mol-1) are more stable than the FU-AT ones (21.00-30.35 kcal mol-1). Among the complexes, the FU3-AT1 and FU3-GC3 are the most stable structures in the both series, which can be related to the sites with the highest affinity. Second, a detail analysis of the hydrogen bond descriptors were performed to elucidate the effect of FU on the strength of HB interactions within the base pairs. Interestingly, due to the formation of various interactions between the active sites of basic molecules, the strength of HB within the base pairs in the most cases increase about +2.75 and +.57 kcal mol-1 for the GC and AT nucleobases, respectively. Finally, several aromatic indices (HOMA, FLU, NICS (0) and NICS (1)) were applied to evaluate the significance of π-electron delocalization (π-ED) of 5/6 membered rings. These results clearly show that the π-ED of the benchmark systems increase with the formation or strengthening of the HB, which is in line with the resonance assisted hydrogen bond theory.