Tunneling splittings in the vibrationally excited states of water trimer.

Tunneling splitting (TS) patterns in vibrationally excited states of the water trimer are calculated, taking into account six tunneling pathways that describe the flips of free OH bonds and five bifurcation mechanisms that break and reform hydrogen bonds in the trimer ring. A tunneling matrix (TM) model is used to derive the energy shifts due to tunneling in terms of the six distinct TM elements in symbolic form. TM elements are calculated using the recently-developed modified WKB (Wentzel-Kramers-Brillouin) method in full dimensionality. Convergence was achieved for the lowest six excited vibrational modes. Bifurcation widths of the pseudorotational quartets are shown to be of comparable size to the ground-state widths, obtained using instanton theory, or increased for some particular modes of vibration. The largest increase is obtained for the excited out-of-phase flip of two adjacent water monomers with free OH bonds pointing in opposite directions relative to the ring plane. Bifurcation widths in (D2O)3 are found to be two orders of magnitude smaller than in (H2O)3. Geometrical arguments were used to explain the order of states in some TS multiplets in vibrationally excited water trimers.

Tunneling splittings using modified WKB method in Cartesian coordinates: The test case of vinyl radical.

Modified WKB theory for calculating tunneling splittings in symmetric multi-well systems in full dimensionality is re-derived using Cartesian coordinates. It is explicitly shown that the theory rests on the wavefunction that is exact for harmonic potentials. The theory was applied to calculate tunneling splittings in vinyl radical and some of its deuterated isotopologues in their vibrational ground states and the low-lying vibrationally excited states and compared to exact variational results. The exact results are reproduced within a factor of 2 in most states. Remarkably, all large enhancements of tunneling splittings relative to the ground state, up to three orders in magnitude in some excited mode combinations, are well reproduced. It is also shown that in the asymmetrically deuterated vinyl radical, the theory correctly predicts the states that are localized in a single well and the delocalized tunneling states. Modified WKB theory on the minimum action path is computationally inexpensive and can also be applied without modification to much larger systems in full dimensionality; the results of this test case serve to give insight into the expected accuracy of the method.

Kinetics of Flavonoid Degradation and Controlled Release from Functionalized Magnetic Nanoparticles.

Flavonoids are naturally occurring antioxidants that have been shown to protect cell membranes from oxidative stress and have a potential use in photodynamic cancer treatment. However, they degrade at physiological pH values, which is often neglected in drug release studies. Kinetic study of flavonoid oxidation can help to understand the mechanism of degradation and to correctly analyze flavonoid release data. Additionally, the incorporation of flavonoids into magnetic nanocarriers can be utilized to mitigate degradation and overcome their low solubility, while the release can be controlled using magnetic fields (MFs). An approach that combines alternating least squares (ALS) and multilinear regression to consider flavonoid autoxidation in release studies is presented. This approach can be used in general cases to account for the degradation of unstable drugs released from nanoparticles. The oxidation of quercetin, myricetin (MCE), and myricitrin (MCI) was studied in PBS buffer (pH = 7.4) using UV-vis spectrophotometry. ALS was used to determine the kinetic profiles and characteristic spectra, which were used to analyze UV-vis data of release from functionalized magnetic nanoparticles (MNPs). MNPs were selected for their unique magnetic properties, which can be exploited for both targeted drug delivery and control over the drug release. MNPs were prepared and characterized by X-ray diffraction, infrared spectroscopy, scanning electron microscopy, superconducting quantum interference device magnetometer, and electrophoretic mobility measurements. Autoxidation of all three flavonoids follows a two-step first-order kinetic model. MCE showed the fastest degradation, while the oxidation of MCI was the slowest. The flavonoids were successfully loaded into the prepared MNPs, and the drug release was described by the first-order and Korsmeyer-Peppas models. External MFs were utilized to control the release mechanism and the cumulative mass of the flavonoids released.

Puncturing lipid membranes: onset of pore formation and the role of hydrogen bonding in the presence of flavonoids.

Products of lipid peroxidation induce detrimental structural changes in cell membranes, such as the formation of water pores, which occur in the presence of lipids with partially oxidized chains. However, the influence of another class of products, dicarboxylic acids, is still unclear. These products have greater mobility in the lipid bilayer, which enables their aggregation and the formation of favorable sites for the appearance of pores. Therefore, dodecanedioic acid (DDA) was selected as a model product. Additionally, the influence of several structurally different flavonoids on DDA aggregation via formation of hydrogen bonds with carboxyl groups was investigated. The molecular dynamics of DDA in DOPC lipid bilayer revealed the formation of aggregates extending over the hydrophobic region of the bilayer and increasing its polarity. Consequently, water penetration and the appearance of water wires was observed, representing a new step in the mechanism of pore formation. Furthermore, DDA molecules were found to interact with lipid polar groups, causing them to be buried in the bilayer. The addition of flavonoids to the system disrupted aggregate formation, resulting in the displacement of DDA molecules from the center of the bilayer. The placement of DDA and flavonoids in the lipid bilayer was confirmed by small-angle X-ray scattering. Atomic force microscopy and electron paramagnetic resonance were used to characterize the structural properties. The presence of DDA increased bilayer roughness and decreased the ordering of lipid chains, confirming its detrimental effects on the membrane surface, while flavonoids were found to reduce or reverse these changes.

Anticooperativity of Multiple Halogen Bonds and Its Effect on Stoichiometry of Cocrystals of Perfluorinated Iodobenzenes.

To investigate influences on the topicity of perfluorinated halobenzenes as halogen bond (XB) donors in the solid state, we have conducted a database survey and prepared 18 novel cocrystals of potentially ditopic (13ditfb, 14ditfb) and tritopic (135titfb) XB donors with 15 monotopic pyridines. 135titfb shows high tendency to be mono- or ditopic, but with strong bases it can act as a tritopic XB donor. DFT calculations have shown that binding of a single acceptor molecule on one of the iodine atoms of the XB donor reduces the ESPmax on the remaining iodine atoms and dramatically decreases their potential for forming further halogen bonds, which explains both the high occurrence of crystal structures where the donors do not achieve their maximal topicity and the observed differences in halogen bond lengths. Despite the fact that this effect increases with the basicity of the acceptor, when the increase of halogen bond energy due to the basicity of the acceptor compensates its decrease due to the reduction of the acidity of the donor, it enables strong bases to form cocrystals in which a potentially polytopic XB donor achieves its maximal topicity.

Vibrational Tunneling Spectra of Molecules with Asymmetric Wells: A Combined Vibrational Configuration Interaction and Instanton Approach.

A combined approach that uses the vibrational configuration interaction (VCI) and semiclassical instanton theory was developed to study vibrational tunneling spectra of molecules with multiple wells in full dimensionality. The method can be applied to calculate low-lying vibrational states in the systems with an arbitrary number of minima, which are not necessarily equal in energy or shape. It was tested on a two-dimensional double-well model system and on malonaldehyde, and the calculations reproduced the exact quantum mechanical (QM) results with high accuracy. The method was subsequently applied to calculate the vibrational spectrum of the asymmetrically deuterated malonaldehyde with nondegenerate vibrational frequencies in the two wells. The spectrum is obtained at a cost of single-well VCI calculations used to calculate the local energies. The interactions between states of different wells are computed semiclassically using the instanton theory at a comparatively negligible computational cost. The method is particularly suited to systems in which the wells are separated by large potential barriers and tunneling splittings are small, for example, in some water clusters, when the exact QM methods come at a prohibitive computational cost.

Tunnelling splitting patterns in some partially deuterated water trimers.

We apply our recently developed semiclassical method for calculating tunnelling splittings (TS) in asymmetric systems to make the first characterization of the ground-state TS pattern of some partially deuterated water trimers. Similarly to homoisotopic water trimers, the ground-state TS patterns are explained in terms of six distinct rearrangement mechanisms. TS patterns in (D2O)(H2O)2 and (H2O)(D2O)2 are composed of sextets induced by the dynamics of flips, and each of its levels is further finely split into a quartet of doublets and a doublet of quartets, respectively, due to various bifurcation dynamics. The TS pattern is obtained using 18 distinct tunnelling matrix elements. TS patterns of (HOD)(H2O)2 and (HOD)(D2O)2 each consists of two sextets, belonging to in-bond and out-of-bond substituted isomers. These sextet levels are further split into quartets by bifurcations. The TS pattern is computed in terms of 13 matrix elements. We also derive analytic expressions for bifurcation tunnelling splittings in terms of tunnelling matrix elements using symmetry. The present approach can be applied to other water clusters and also to the low-lying vibrationally excited states and should help in the interpretation and assignment of experimental spectra in the future.

Tunneling splittings of vibrationally excited states using general instanton paths.

A multidimensional semiclassical method for calculating tunneling splittings in vibrationally excited states of molecules using Cartesian coordinates is developed. It is an extension of the theory by Mil'nikov and Nakamura [J. Chem. Phys. 122, 124311 (2005)] to asymmetric paths that are necessary for calculating tunneling splitting patterns in multi-well systems, such as water clusters. Additionally, new terms are introduced in the description of the semiclassical wavefunction that drastically improves the splitting estimates for certain systems. The method is based on the instanton theory and builds the semiclassical wavefunction of the vibrationally excited states from the ground-state instanton wavefunction along the minimum action path and its harmonic neighborhood. The splittings of excited states are thus obtained at a negligible added numerical effort. The cost is concentrated, as for the ground-state splittings, in the instanton path optimization and the hessian evaluation along the path. The method can thus be applied without modification to many mid-sized molecules in full dimensionality and in combination with on-the-fly evaluation of electronic potentials. The tests were performed on several model potentials and on the water dimer.

Instanton theory of ground-state tunneling splittings with general paths.

We derive a multidimensional instanton theory for calculating ground-state tunneling splittings in Cartesian coordinates for general paths. It is an extension of the method by Mil'nikov and Nakamura [J. Chem. Phys. 115, 6881 (2001)] to include asymmetric paths that are necessary for calculating tunneling splitting patterns in multi-well systems, such as water clusters. The approach avoids multiple expensive matrix diagonalizations to converge the fluctuation prefactor in the ring-polymer instanton (RPI) method, and instead replaces them by an integration of a Riccati differential equation. When combined with the string method for locating instantons, we avoid the need to converge the calculation with respect to the imaginary time period of the semiclassical orbit, thereby reducing the number of convergence parameters of the optimized object to just one: the number of equally spaced system replicas used to represent the instanton path. The entirety of the numerical effort is thus concentrated in optimizing the shape of the path and evaluating hessians along the path, which is a dramatic improvement over RPI. In addition to the standard instanton approximations, we neglect the coupling of vibrational modes to external rotations. The method is tested on the model potential of malonaldehyde and on the water dimer and trimer, giving close agreement with RPI at a much-reduced cost.

A Crystallographic Charge Density Study of the Partial Covalent Nature of Strong N⋠⋠⋠Br Halogen Bonds.

The covalent nature of strong N-Br⋅⋅⋅N halogen bonds in a cocrystal (2) of N-bromosuccinimide (NBS) with 3,5-dimethylpyridine (lut) was determined from X-ray charge density studies and compared to a weak N-Br⋅⋅⋅O halogen bond in pure crystalline NBS (1) and a covalent bond in bis(3-methylpyridine)bromonium cation (in its perchlorate salt (3). In 2, the donor N-Br bond is elongated by 0.0954 Å, while the Br⋅⋅⋅acceptor distance of 2.3194(4) is 1.08 Šshorter than the sum of the van der Waals radii. A maximum electron density of 0.38 e Å-3 along the Br⋅⋅⋅N halogen bond indicates a considerable covalent contribution to the total interaction. This value is intermediate to 0.067 e Å-3 for the Br⋅⋅⋅O contact in 1, and approximately 0.7 e Å-3 in both N-Br bonds of the bromonium cation in 3. A calculation of the natural bond order charges of the contact atoms, and the σ*(N1-Br) population of NBS as a function of distance between NBS and lut, have shown that charge transfer becomes significant at a Br⋅⋅⋅N distance below about 3 Å.