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Lanthanide ions (Ln3+) show similar physicochemical properties in aqueous solutions, wherein they exist as + 3 cations and exhibit ionic radii differences of less than 0.26 Å. A flexible linear peptide lanthanide binding tag (LBT), which recognizes a series of 15 Ln3+, shows an interesting characteristic in binding specificity, i.e., binding affinity biphasically changes with an increase in the atomic number, and shows a greater than 60-fold affinity difference between the highest and lowest values. Herein, by combining experimental and computational investigations, we gain deep insight into the reaction mechanism underlying the specificity of LBT3, an LBT mutant, toward Ln3+. Our results clearly show that LBT3-Ln3+ binding can be divided into three, and the large affinity difference is based on the ability of Ln3+ in a complex to be directly coordinated with a water molecule. When the LBT3 recognizes a Ln3+ with a larger ionic radius (La3+ to Sm3+), a water molecule can interact with Ln3+ directly. This extra water molecule infiltrates the complex and induces dissociation of the Asn5 sidechain (one of the coordinates) from Ln3+, resulting in a destabilizing complex and low affinity. Conversely, with recognition of smaller Ln3+ (Sm3+ to Yb3+), the LBT3 completely surrounds the ions and constructs a stable high affinity complex. Moreover, when the LBT3 recognizes the smallest Ln3+, namely Lu3+, although it completely surrounds Lu3+, an entropically unfavorable phenomenon specifically occurs, resulting in lower affinity than that of Yb3+. Our findings will be useful for the design of molecules that enable the distinction of sub-angstrom size differences.

Hydrophilic ions in oil phase tend to be hydrated in the presence of trace water and form hydrated clusters. The present paper elucidates the equilibrium size distribution of hydrated ion clusters and the microscopic rates of adsorption and desorption of water with the help of molecular dynamics simulations. The size distribution is derived from reversible work of hydration, which is nearly constant over the hydration number except for small clusters. The intrinsic rate constants of adsorption and desorption are evaluated to be in several psec order after correcting the diffusion. The microscopic hydration properties of ions in the oil phase play key roles in chemical reactions involving both hydrophilic and hydrophobic reactants as well as in the transport and reactivity of the ions in oil phase and at the water-oil interface.

We propose a method of automatic pattern decomposition for mixed spectra, based on non-negative matrix factorization. This method uses a regularization term that increases the volume coordinated by the decomposed bases. This treatment enhances dissimilarities among the bases and is suitable for expressing the natural component bases of spectra, which generally differ from each other. This regularization term shows better accuracy in a test using virtual spectrum datasets compared to conventional regularizations. We also test the proposed method with a high-throughput X-ray diffraction dataset measured in a synchrotron radiation facility. Our method can decompose the dataset into component bases, which are correctly assigned to background and chemical compounds, while results obtained by other regularization terms cannot sufficiently separate background peaks from meaningful peaks. We also found that a combination of dissimilarity regularization with smoothness regularization can detect small meaningful peaks. These results show the advantage of dissimilarity regularization for the purpose of automatic spectrum decompositions.

Microscopic mechanism of ion transport through water-oil interface was investigated with molecular dynamics simulation. The formation/breaking of a water finger during the ion passage was explicitly formulated in the free energy surface. The calculated 2D free energy surface clearly revealed a hidden barrier of ion passage accompanied by the water finger. This barrier elucidates the retarded rate of interfacial ion transfer.

Surface acidity/basicity of water has been elusive, due to contradicting observations from various aspects. One effective definition has been proposed by investigating the protonation equilibrium (pKa) of the indicator species at the water surface. We calculated the pKa of trimethylamine at the surface by using quantum mechanics/molecular mechanics (QM/MM) and thermodynamic integration calculations and elucidated the observed pKa shift at the surface. It was revealed that the observed pKa shift reflects specific properties of the indicator species, particularly relative solvation free energy at the surface. The pKa shift appears within ∼5 A thickness. One has to properly take account of the specific indicators toward deriving a general picture of surface acidity/basicity from protonation reactions.

A tip-enhanced Raman spectroscopy (TERS) set-up added on a scanning tunneling microscope (STM) was constructed and was used to study the molecular arrangement of 4,4′-bipyridine (4,4′-BiPy) and 4,4′-bipyridine N,N' -dioxide (4,4′-BiPyO 2 ) adsorbed on Au(111). Over a monolayer of 4,4′-BiPy, in the ambient atmosphere, intense TERS signals were recorded, involving Au N stretching vibration at 185 cm − 1 . At the early stage of 4,4′-BiPy adsorption, the Au N stretching signal was not detected. By the aid of the theoretical calculations of the Raman scattering intensities for each vibrational normal mode, a standing-up, tilted orientation at monolayer coverage and a vertical orientation with the longitudinal molecular axis parallel to the surface at low surface coverage was concluded. Adsorption of 4,4′-BiPyO 2 on Au(111) resulted in formation of a (6 × 9) adlattice. Moderately intense TERS signals were observed, containing the N O stretching modes and the in-plane ring vibrational modes. Neither Au O nor Au N stretching modes were observed. 4,4′-BiPyO 2 was laid with the longitudinal axis parallel to the surface, and the molecular plane vertical to the surface. These results demonstrate that STM-TERS is an effective method for simultaneous imaging and vibrational analysis, facilitating identification of the adsorbed layers with the nanometer-scale spatial resolution and monolayer sensitivity.

Microscopic mechanism of phase transfer catalyst (PTC) is investigated by molecular dynamics simulation. As an example of PTC, tetrabutylammonium cation is treated which facilitates Cl - transfer from water to chloroform phase. Calculated free energy profiles reveal the effects of PTC in relation to the pertinent change of interface structure. The ion pair formation changes the free energy profiles in the late stage of transfer, where large structural fluctuation emerges, called water finger. The PTC controls the formation of water finger and thereby influences on the free energy. These microscopic insight is important for PTC-assisted reactions at the interface.

The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor. Patient 1 was a 43-year-old male with major portal tumor thrombi. He received combination therapy consisting of continuous arterial infusion (MTX 30 mg/m2, day 1, CDDP/5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Patient 2 was a 66-year-old male with major hepatic venous tumor thrombi. He received combination therapy consisting of continuous arterial infusion (5-FU 6 mg/m2: 250 mg/m2, day 1-14) and subcutaneous injection of IFN-alpha (500 x 10(4) U, 3 times a week, 4 weeks). Decrease in tumor was observed in both patients markers and marked regression of tumor was observed in both patients. They are still in complete response. This combination therapy is an effective strategy for advanced HCC.