Explicit Water Molecules Research Articles

Theoretical Assessment of Carbon Dioxide Reactivity in Methylpiperidines: A Conformational Investigation.

In this work, the possible mechanisms for the reactions of CO2 with various positional isomers of methylpiperidines (MPs) (N-MP, 2-MP, 3-MP, and 4-MP) including the effect of aqueous solvation have been explored using quantum chemical methods. The major pathways investigated for CO2 capture in aqueous amines are carbamate formation, its hydrolysis, and the bicarbonate formation (CO2 + H2O + MP) reaction. The calculations indicate that an axial orientation for the methyl group and an equatorial for the COO- group could be energetically ideal in the carbamate product of MPs. The proton abstraction step in the carbamate pathway is almost barrierless for the zwitterion-amine route, while a much higher energy barrier is observed for the zwitterion-H2O route. During carbamate hydrolysis, the addition of even two explicit water molecules does not exhibit any notable effect on the already high energy barrier associated with this reaction. This indicates that bicarbonate formation is less likely to occur via carbamate hydrolysis. The calculations suggest that, although the carbamate pathway is kinetically favored, the MP carbamate could still be a minor product, especially for sterically hindered conformations, and the bicarbonate pathway should be predominant in aqueous MPs.

Cation-Induced Disruption of the Local Structure of Water in Faujasite

The changes in the structure of water confined in faujasite were resolved by a series of ab initio molecular dynamic simulations of explicit water molecules in faujasite with varying Si/Al ratio and counterions present. Radial distribution functions of water oxygen atom pairs, as well as counterions to Al pairs, were calculated to quantify the structure of water in faujasite and the distribution of counterions in the water-filled faujasite pores. Radial distribution functions reveal that confinement without counterions results in more water molecules hydrogen bound to each other. In hydrogen-exchanged faujasite, the increase in aluminum content led to the disruption of the confined water structure as charge-compensating protons dissociated from Al tetrahedra and entered the liquid water in the pores. In addition, a potential of mean force of proton transfer shows that protons are thermodynamically favored to be in the liquid water rather than bound on Al tetrahedra. Exchanged Na+ and La3+ counterions, which remain closer to Al tetrahedra in liquid water than H+, also disordered the confined water structure. Two La3+ ions disrupted water less than did six Na+ ions, suggesting that, for the alkali and lanthanide ions, the number of counterions in FAU has a larger effect on the structure of water than the charge of the ion itself.

Probing the water hydrogen-bonding effects on the ground and low-lying excited states of phenanthroline isomers

In this work, the ground and low-lying excited states of a series of phenanthroline isomers (1,10-phenanthroline, 1,7-phenanthroline, and 4,7-phenanthroline) were investigated. Density functional theory (DFT) was used for determining the structural and energetic properties connected to the ground state (such as bond lengths and angles, hydrogen-bond interactions, vibrational frequencies, and relative energies) of each molecule while time-dependent DFT was employed for probing the excited state parameters (excitation energies, oscillator strengths, and structures); both approaches were used in combination with the CAM-B3LYP exchange–correlation functional and the cc-pVTZ basis set. The computations were performed in the gas-phase and water. The effects originating from the interactions with the solvent environment were examined by means of the integral equation formalism polarizable continuum model (IEF-PCM), as well as using a composite solvation model (CSM) through the incorporation of explicit water molecules in combination with IEF-PCM. In terms of relative stability, 1,10-phenanthroline became the most stable isomer when the combined implicit-explicit solvation was taken into account, an interesting behavior that may be assigned to the existence of a chain of hydrogen-bond interactions involving the two explicitly added water molecules and both nitrogen atoms from 1,10-phenanthroline. This feature provided better stabilization to the system when compared to the 1,7-phenanthroline and 4,7-phenanthroline. Taking the 1,10-phenanthroline isomer as an example, all its low-lying singlet excited states were determined to have non-zero oscillator strengths when the CSM was used and, more importantly, one among these states was found as being highly accessible (with oscillator strength = 0.9545). From the comparison with the results obtained using solely the implicit solvation (IEF-PCM results), it is possible to assign the presence of the hydrogen-bond interactions as being an important factor for making such excited state likely to be accessed.

Mechanism for dissociative hydrolysis of pyrimidine nucleoside d4N: Inversion vs retention

Employing the microhydration model that involves two to five explicit water molecules, two plausible dissociative hydrolysis pathways of 2′,3′-didehydro-2′,3′-dideoxyuridine (d4U), α-path with configuration-inversion and β-path with configuration-retention, have been investigated by M06-2X(CPCM)/6–31++G(d,p) method. Using this model, inclusion of three explicit water molecules (n = 3) is shown to be the smallest system that gives the minimal activation free energy for α-path and β-path. Our results suggest that the glycoside cleavage is the RDS, and α-path is more favorable kinetically than β-path. Whereas β-path with exergonic formation of β-dihydrofuran-like sugar with keto pyrimidine complex possesses thermodynamic preference over α-path, where the formation of α-dihydrofuran-like sugar with enol pyrimidine complex is endergonic. The free energy barriers of RDSs for d4U (25.8 kcal mol−1) and d4T (27.3 kcal mol−1) suggest that the glycosidic bond in d4T is more stable than that in d4U. The relative lower stability of d4U is probably an important factor for less antiviral activity of d4U. The small free energy barrier differences of ∼ 1 kcal mol−1 for β-path over α-path, and the reaction free energy differences of ∼ -12 kcal mol−1 for β-path lower than α-path in d4T and d4U suggest a competitive β-path in pyrimidine d4Ns. The higher free energy barriers of RDSs in ddU (27.6 kcal mol−1) and ddT (29.0 kcal mol−1) indicate that the saturated sugar moiety increases the stability of glycosidic bond in contrast to the unsaturated counter parts in d4U and d4T. NBO analysis also shows the kinetic preference of α-path over β-path. Our results provide an exploration for the less antiviral activity of d4U and the influence of saturated ribose on the glycosidic bond stability of pyrimidine d4Ns.

Differences in solvation thermodynamics of oxygenates at Pt/Al2O3 perimeter versus Pt(111) terrace sites

A prominent role of water in aqueous-phase heterogeneous catalysis is to modify free energies; however, intuition about how is based largely on pure metal surfaces or even homogeneous solutions. Using multiscale modeling with explicit liquid water molecules, we show that the influence of water on the free energies of adsorbates at metal/support interfaces is different than that on pure metal surfaces. We specifically compute free energies of solvation for methanol and its constituents on a Pt/Al2O3 catalyst and compare the results to analogous values calculated on a pure Pt catalyst. We find that the more hydrophilic Pt/Al2O3 interface leads to smaller (more positive) free energies of solvation due to an increased entropy penalty resulting from the additional work necessary to disrupt the interfacial water structure and accommodate the interfacial species. The results will be of interest in other fields, including adsorption and proteins.

Insight into the role of excess hydroxide ions in silicate condensation reactions.

The formation of silicate oligomers in the early stages is key to zeolite synthesis. The pH and the presence of hydroxide ions are important in regulating the reaction rate and the dominant species in solutions. This paper describes the formation of silicate species, from dimers to 4-membered rings, using ab initio molecular dynamics simulations in explicit water molecules with an excess hydroxide ion. The thermodynamic integration method was used to calculate the free energy profile of the condensation reactions. The hydroxide group's role is not only to control the pH of the environment, but also to actively participate in the condensation reaction. The results show that the most favorable reactions are linear-tetramer and 4-membered-ring formation, with overall barriers of 71 kJ mol-1 and 73 kJ mol-1, respectively. The formation of trimeric silicate, with the largest free-energy barrier of 102 kJ mol-1, is the rate-limiting step under these conditions. The excess hydroxide ion aids in the stabilization of the 4-membered-ring structure over the 3-membered-ring structure. Due to a relatively high free-energy barrier, the 4-membered ring is the most difficult of the small silicate structures to dissolve in the backward reaction. This study is consistent with the experimental observation that silicate growth in zeolite synthesis is slower in a very-high-pH environment.

Target-ligand binding affinity from single point enthalpy calculation and elemental composition.

Reliable target-ligand binding thermodynamics data are essential for successful drug design and molecular engineering projects. Besides experimental methods, a number of theoretical approaches have been introduced for the generation of binding thermodynamics data. However, available approaches often neglect electronic effects or explicit water molecules influencing target-ligand interactions. To handle electronic effects within a reasonable time frame, we introduce a fast calculator QMH-L using a single target-ligand complex structure pre-optimized at the molecular mechanics level. QMH-L is composed of the semi-empirical quantum mechanics calculation of binding enthalpy with predicted explicit water molecules at the complex interface, and a simple descriptor based on the elemental composition of the ligand. QMH-L estimates the target-ligand binding free energy with a root mean square error (RMSE) of 0.94 kcal mol-1. The calculations also provide binding enthalpy values and they were compared with experimental binding thermodynamics data collected from the most reliable isothermal titration calorimetry studies of systems including various protein targets and challenging, large peptide ligands with a molecular weight of up to 2-3 thousand. The single point enthalpy calculations of QMH-L require modest computational resources and are based on short runs with open source and/or free software like Gromacs, Mopac, MobyWat, and Fragmenter. QMH-L can be applied for fast, automated scoring of drug candidates during a virtual screen, enthalpic engineering of new ligands or thermodynamic explanation of complex interactions.

The peptide bond rupture mechanism in the serine proteases: an in silico study based on sequential scale models.

Given the importance of serine proteases for biochemical processes, we have studied the peptide bond rupture mechanism using three sequential scale models as representations of the KLK5 enzyme (a protein overexpressed in ovarian cancer). The first model contains the basic functional groups of the residues that conform to the catalytic triad present in serine proteases; the second model contains some additional residues and, finally, the last representation includes all atoms of the KLK5 protein together with 10.000 explicit water molecules. This separation into three scale models allows us to separate the intrinsic reactivity of the catalytic triad from the process taking place in the enzyme. The methodologies employed in this work include full DFT calculations with a dielectric continuum in the first two models and a multi-level setup with a Quantum Mechanics/Molecular Mechanics (QM/MM) partition in the whole protein system. Our results show that the peptide-bond rupture mechanism is a stepwise process involving two proton transfer reactions. The rate-determining step is the second proton transfer from the imidazole group to the amidic nitrogen of the substrate. In addition, we find that the simplest model does not provide accurate results compared to the full protein system. This can be attributed to the electronic stabilization conferred by the residues around the reaction site. Interestingly, the energy profile obtained with the second scale model with additional residues shows the same trends as the full system and could therefore be considered an appropriate model system. It could be used for studying the peptide bond rupture mechanism in case full QM/MM calculations cannot be performed, or as a rapid tool for screening purposes.

Solvent effect of water on the UV-B absorption of plant sunscreen agents

These authors contributed equally to this work. UV-B (280-320 nm) sunscreening is crucial for lives on Earth. Examining the role of surrounding of UV-B screening molecules can help us better understand UV-B absorption. Water is ubiquitous in cells as the solvent, but its impacts on UV-B absorption of sunscreen agents are underexplored. Herein, we report a first-principle study on UV-B absorption of sinapate malate (SM) and relevant molecular species, with a focus on the solvent effect of water. The capability of UV-B screening by anions of SM, the proposed species for actual sunscreening, is shaped by water. Both the implicit water providing the dielectric environment of solvation and the explicit water molecules forming hydrogen bonding to SM anion can appreciably alter the nature of transition orbitals responsible to the UV-B absorption of the anion. Finally, we find the molecular dipole moment of an organic UV-B screening agent can be an indicator of its UV-B screening sensitivity to the surrounding water. Our work may serve as a starting point of developing new water-soluble UV-B screening agent.

Aldehyde Hydrogenation by Pt/TiO2 Catalyst in Aqueous Phase: Synergistic Effect of Oxygen Vacancy and Solvent Water.

The aldehyde hydrogenation for stabilizing and upgrading biomass is typically performed in aqueous phase with supported metal catalysts. By combining density functional theory calculations and ab initio molecular dynamics simulations, the model reaction of formaldehyde hydrogenation with a Pt/TiO2 catalyst is investigated with explicit solvent water molecules. In aqueous phase, both the O vacancy (Ov) on support and solvent molecules could donate charges to a Pt cluster, where the Ov could dominantly reduce the Pt cluster from positive to negative. During the formaldehyde hydrogenation, the water molecules could spontaneously protonate the O in the aldehyde group by acid/base exchange, generating the OH* at the metal-support interface by long-range proton transfer. By comparing the stoichiometric and reduced TiO2 support, it is found that the further hydrogenation of OH* is hard on the positively charged Pt cluster over stoichiometric TiO2. However, with the presence of Ov on reduced support, the OH* hydrogenation could become not only exergonic but also kinetically more facile, which prohibits the catalyst from poisoning. This mechanism suggests that both the proton transfer from solvent water molecules and the easier OH* hydrogenation from Ov could synergistically promote aldehyde hydrogenation. That means, even for such simple hydrogenation in water, the catalytic mechanism could explicitly relate to all of the metal cluster, oxide support, and solvent waters. Considering the ubiquitous Ov defects in reducible oxide supports and the common aqueous environment, this synergistic effect may not be exclusive to Pt/TiO2, which can be crucial for supported metal catalysts in biomass conversion.

An Accurate Approach for Computational pKa Determination of Phenolic Compounds

Computational chemistry is a valuable tool, as it allows for in silico prediction of key parameters of novel compounds, such as pKa. In the framework of computational pKa determination, the literature offers several approaches based on different level of theories, functionals and continuum solvation models. However, correction factors are often used to provide reliable models that adequately predict pKa. In this work, an accurate protocol based on a direct approach is proposed for computing phenols pKa. Importantly, this methodology does not require the use of correction factors or mathematical fitting, making it highly practical, easy to use and fast. Above all, DFT calculations performed in the presence two explicit water molecules using CAM-B3LYP functional with 6-311G+dp basis set and a solvation model based on density (SMD) led to accurate pKa values. In particular, calculations performed on a series of 13 differently substituted phenols provided reliable results, with a mean absolute error of 0.3. Furthermore, the model achieves accurate results with -CN and -NO2 substituents, which are usually excluded from computational pKa studies, enabling easy and reliable pKa determination in a wide range of phenols.

Absolute Hydration Free Energy of Small Anions and the Aqueous pKa of Simple Acids.

Heats of formation and gas phase acidities for the simple acids and their deprotonated anions (A- = F-, Cl-, Br-, I-, OH-, SH-, SeH-, TeH-, OCl-, OBr-, and OI-) were calculated using the Feller-Peterson-Dixon (FPD) method with large basis sets including Douglass-Kroll scalar relativistic corrections. Hydration of the neutral and anionic species was predicted using the supermolecule-continuum approach, resulting in absolute hydration free energies that, when combined with calculated gas phase acidities, produce aqueous acidities and pKa values for these simple acids that are, in general, in excellent agreement with experimental literature values. Absolute hydration free energy values converged quickly in terms of the experimental values for neutral species, requiring only four explicit H2O molecules. HI is anomalous in that it fully dissociates ionically in a water tetramer and was treated without explicit water molecules. The hydration energies of anionic species converged more slowly and were modeled with up to 16 explicit H2O molecules. Calculated values for ΔHf and ΔGgas agree with experimental values within ca. 1.2 kcal/mol, and ΔGaq and ΔΔGhyd agree with experimental values within ca. 2 kcal/mol in most cases.

Quantum chemical modeling of the thermodynamics of the formation of Au(III), Pd(II), and Pt(II) chloride complexes.

Quantitative prediction of physical properties of liquids and equilibrium constants is important for many applications. Computational methods based on either explicit or implicit solvent models can be used to approximate thermodynamics of complexation. A practical method for calculating the stability constant of d8 chlorocomplexes (PdCl42-, PtCl42-, AuCl4-) in aqueous solution has been developed by using DFT and DLPNO-CCSD with the SMD solvation model and 100 unique explicit water molecules. Stability constants have been calculated by using methods, such as DFT/PBE0-D3, DLPNO-CCSD, DLPNO-CCSD-DK, and DLPNO-CCSD(T), and basis sets, such as def2-TZVPD, def2-TZVPP, ma-def2-TZVP, ma-DKH-def2-TZVP, SARC-TZVP, and SARC-TZVPP. Calculations using DFT/PBE0-D3/def2-TZVPD and DLPNO-CCSD-DK/ma-DKH-Def2-TZVP/SARC-DKH-TZVP with SMD solvation with explicit waters are found to have errors of 2-3 logunits relative to experimental data. The best results are obtained by using 8 explicit waters for d8 aqua complexes, 14 explicit waters for d8 chlorocomplexes, and 4 explicit waters for chloride ion.

Adsorption free energy of phenol onto coronene: Solvent and temperature effects

Molecular modeling can considerably speed up the discovery of materials with high adsorption capacity for wastewater treatment. Despite considerable efforts in computational studies, the molecular modeling of adsorption processes has several limitations in reproducing experimental conditions. Handling the environmental effects (solvent effects) and the temperature effects are part of the important limitations in the literature. In this work, we address these two limitations using the adsorption of phenol onto coronene as case study. In the proposed model, for the solvent effects, we used a hybrid solvation model, with n explicit water molecules and implicit solvation. We increasingly used n=1 to n=12 explicit water molecules. To account for the temperature effects, we evaluated the adsorption efficiency using the adsorption free energy for temperatures varying from 200 to 400K. We generated initial configurations using classical molecular dynamics, before further optimisation at the ωB97XD/aug-cc-pVDZ level of theory. Polarisable continuum solvation model (PCM) is used for the implicit solvation. The adsorption free energy is evaluated to be -1.3kcal/mol at room temperature. It has been found that the adsorption free energy is more negative at low temperatures. Above 360K, the adsorption free energy is found to be positive.

AMOEBA Force Field Trajectories Improve Predictions of Accurate pKa Values of the GFP Fluorophore: The Importance of Polarizability and Water Interactions.

Precisely quantifying the magnitude, direction, and biological functions of electric fields in proteins has long been an outstanding challenge in the field. The most widely implemented experimental method to measure such electric fields at a particular residue in a protein has been through changes in pKa of titratable residues. While many computational strategies exist to predict these values, it has been difficult to do this accurately or connect predicted results to key structural or mechanistic features of the molecule. Here, we used experimentally determined pKa values of the fluorophore in superfolder green fluorescent protein (GFP) with amino acid mutations made at position Thr 203 to evaluate the pKa prediction ability of molecular dynamics (MD) simulations using a polarizable force field, AMOEBA. Structure ensembles from AMOEBA were used to calculate pKa values of the GFP fluorophore. The calculated pKa values were then compared to trajectories using a conventional fixed charge force field (Amber03 ff). We found that the position of water molecules included in the pKa calculation had opposite effects on the pKa values between the trajectories from AMOEBA and Amber03 force fields. In AMOEBA trajectories, the inclusion of water molecules within 35 Å of the fluorophore decreased the difference between the predicted and experimental values, resulting in calculated pKa values that were within an average of 0.8 pKa unit from the experimental results. On the other hand, in Amber03 trajectories, including water molecules that were more than 5 Å from the fluorophore increased the differences between the calculated and experimental pKa values. The inaccuracy of pKa predictions determined from Amber03 trajectories was caused by a significant stabilization of the deprotonated chromophore's free energy compared to the result in AMOEBA. We rationalize the cutoffs for explicit water molecules when calculating pKa to better predict the electrostatic environment surrounding the fluorophore buried in GFP. We discuss how the results from this work will assist the prospective prediction of pKa values or other electrostatic effects in a wide variety of folded proteins.

Aligning Electronic Energy Levels in Pyridine-Assisted CO2 Activation at the GaP(110)/Water Interface Using Ab Initio Molecular Dynamics

Photoelectrochemical CO2 reduction has attracted considerable attention as a route to convert CO2 into value-added products. Pyridine (Py)-catalyzed CO2 reduction on a GaP photoelectrode has been shown to be a promising photoelectrochemical system to produce methanol under the underpotential condition. However, whether the dramatic decrease in overpotential can be attributed to the CO2 activation by the formation of the zwitterionic complex PyCO2 is currently under debate. Because the alignment between the band edge positions of photoelectrodes and the redox potentials of species determines the desired redox reactions, calculations have been performed to evaluate the band edge positions of GaP and the redox potentials of relevant reactions. In these works, the water effect has been either neglected or approximated by using the dielectric continuum or a few explicit water molecules, which may not be enough to determine the accurate energy level alignment in realistic chemical environments. Moreover, calculations performed in conventional implicit solvation models suggested that PyCO2 is unstable in homogeneous aqueous, while the bonding interactions between CO2 and N species have been experimentally detected. Thus, we performed ab initio molecular dynamics to investigate the band alignment of GaP, as well as the stability and the reducibility of PyCO2 in more realistic chemical environments. Our results showed that the solvation effect and the pyridine adsorption could shift up the band edge positions of GaP significantly, and neglecting such effects could result in a serious underestimation of the activity of the photocatalysts. More importantly, we found that the interaction between pyridine and CO2 at the GaP(110)/water interface is strong due to the synergetic stabilization effect, which leads to an about 0.6 V less negative redox potential of PyCO2/PyCO2– than that of CO2/CO2– in the homogeneous aqueous. Furthermore, we compared the redox potential of PyCO2/PyCO2– at the GaP(110)/water interface with the conduction band minimum of GaP, which showed that the reduction of the adsorbed PyCO2 is thermodynamically feasible. Our results suggested that the CO2 activation by the formation of PyCO2 at the GaP(110)/water interface could be responsible for the low overpotential. This work provides valuable insights into the mechanism of pyridine-catalyzed CO2 reduction on GaP and could pave the way for the development of efficient catalysts for CO2 reduction.

Antioxidant and anticancer properties of plant‐based bioactive flavonoids cardamonin and alpinetin: A theoretical insight from •OOH antiradical and Cu (II) chelation mechanisms

AbstractA density functional theory (DFT) study aimed at a comparative investigation on the antioxidant mechanisms of cardamonin and alpinetin, two flavonoid bioactive components derived from plant sources with potential medicinal properties, has been performed through assessment of their •OOH scavenging ability in non‐polar medium and Cu (II) chelation ability in the absence and presence of explicit water molecules stabilising the metal cation. In addition, a comparison of the antioxidant properties of cardamonin with the moiety of phloroglucinol and acylated phloroglucinol has been performed to establish cardamonin's antioxidant potentiality among the phloroglucinol family of compounds. The results of the investigation reveal that alpinetin could be considered a better radical scavenger than cardamonin within the non‐polar lipid bilayer medium of biological systems. However, the role of both compounds as •OOH scavengers may be limited, in comparison to standard antioxidant molecules, such as α‐tocopherol, because of the fact that the bond dissociation enthalpy for the hydrogen atom abstraction mechanism has a positive value, which signifies that the radical scavenging mechanism is not a thermodynamically preferred reaction. Cardamonin is found also to be a weaker antioxidant molecule than phloroglucinol and acylated phloroglucinol moieties. In terms of metal chelation mechanism, cardamonin is a better Cu (II) chelator than alpinetin since it has a higher metal ion affinity than alpinetin upon coordination to the Cu (II) cation. The results obtained could also imply that cardamonin is a better agent in dealing with angiogenesis, tumour growth and metastatis stages of cancer than alpinetin, since the ability of chelating metal cation shown by cardamonin ascribes it a better role as an anticancer agent than alpinetin. Therefore, although alpinetin may prove to play an important role as a promising antioxidant and antiinflamatory agent than cardamonin, by scavenging radical species, cardamonin would prove more valuable in the control of various stages of cancer growth than alpinetin.

Effect of intermolecular hydrogen bonds on the proton transfer and fluorescence characteristics of 1′-hydroxy-2′-acetonaphthone

1′-hydroxy-2′-acetonaphthone (HAN) is a useful fluorescence probe based on excited state intramolecular proton transfer (ESIPT). A number of experiments had explored the fluorescence properties of HAN in different microenvironments and applied HAN to bioimaging. However, the mechanism of fluorescence properties of HAN in different microenvironments was not been fully reported. Thus, our research aims to investigate the proton transfer (PT) and fluorescence characteristics of HAN in different microenvironments, focusing on revealing the hydrogen bond dynamics in high-polar aqueous solution (HAN-H2O) and low-polar hydrophobic pocket of bovine serum albumin by the density functional theory (DFT) and time-dependent density functional theory (TD-DFT). Explicit water molecules were placed around HAN to simulate the hydrogen bond interactions between HAN and the water molecules in an aqueous solution. The intermolecular hydrogen bonds slightly affect the geometric structures of HAN, but would inhibit the ESIPT process while increasing the charge transfer distance, leading to red shift of fluorescence. Upon photoexcitation, the intramolecular hydrogen bond had been strengthened, providing the driving force of PT, which resulted in HAN and HAN-H2O undergoing ultrafast ESIPT process. Meanwhile, after photoexcitation, the intermolecular hydrogen bonds were significantly enhanced, decreasing the energy of HAN-H2O in the excited state and promoted the radiationless deactivation of HAN-H2O. Therefore, HAN has weak fluorescence in the aqueous solution.

Predicting octanol/water partition coefficients and pKa for the SAMPL7 challenge using the SM12, SM8 and SMD solvation models.

Blind predictions of octanol/water partition coefficients and pKa at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. Octanol/water partition coefficients were predicted from solvation free energies computed using electronic structure calculations with the SM12, SM8 and SMD solvation models. Within these calculations we compared the use of gas- and solution-phase optimized geometries of the solute. Based on these calculations we found that in general the use of solution phase-optimized geometries increases the affinity of the solutes for water as compared to octanol, with the use of gas-phase optimized geometries resulting in the better agreement with experiment. The pKa is computed using the direct approach, scaled solvent-accessible surface model, and the inclusion of an explicit water molecule, where the latter two methods have previously been shown to offer improved predictions as compared to the direct approach. We find that the use of an explicit water molecule provides superior predictions, and that the predicted macroscopic pKa is sensitive to the employed microstates.

Effect of Microhydration on the Peptide Backbone of N-Acetyl-Phenylalaninylamide (NAPA) Using IR, Raman and Vibrational Chiroptical Spectrosocpies (VCD, ROA): A Computational Study

In this work, N-acetyl-phenylalaninylamide (NAPA) and microhydrated NAPA i.e. [NAPA-A(H2O)n (n = 1-4)] complexes were studied with the aid of density functional theory (DFT) calculation in the gas phase to determine the absolute configuration, hydration effect on amide modes (amide I-IV), the robustness of amide modes, and associated amide modes. IR, Raman, vibrational chiroptical (VCD and ROA) spectra, VCD rotational strength, VCD dipole strength and the angle between the electric transition dipole moment (ETDM) and the magnetic transition dipole moment (MTDM) were performed using DFT/wB97XD/cc-pVTZ level of the computational approach. The absolute configuration (D/L) of the most stable conformer of NAPA (NAPA-A) was confirmed by the analysis of the VCD spectra that show opposite sign, and intensity. Amide I (C=Os) VCD bands are non-robust and amide II-IV (C-Ns, N-Hb and N-Hs) bands are robust and reliable on the basis of the robustness concept. Consequently, the VCD stretching and scissoring modes of NH2 and H2O for [NAPA- A(H2O)n (n=1-4)] complexes are also robust and reliable. On the other hand, ROA calculation confirmed that the C5 interaction in the peptide backbone of NAPA-A is entirely lost in presence of a single configuration of an explicit water molecule. [NAPA-A(H2O)1] complex has a C7 interaction in the peptide backbone which is also lost in the presence of the 2nd and 3rd water molecules. DCPI (180) Raman and DCPI (180) ROA calculations were also performed in the solution phase (implicit water) using the integral equation formalism variant polarizable continuum model (IEF-PCM) to compare the gas phase results.