Joonghan Kim

Volume-conserving trans – cis isomerization pathways in photoactive yellow protein visualized by picosecond X-ray crystallography

Trans-to-cis isomerization, the key reaction in photoactive proteins, cannot usually occur through the standard one-bond-flip mechanism. Due to spatial constraints imposed by a protein environment, isomerization is likely to proceed via a “volume-conserving” mechanism in which highly-choreographed atomic motions are expected, the details of which have not yet been directly observed. Here we employ time-resolved X-ray crystallography to structurally visualize isomerization of the p-coumaric acid chromophore in photoactive yellow protein with 100 picosecond time resolution and 1.6 Å spatial resolution. The structure of the earliest intermediate (IT) resembles a highly-strained transition state in which the torsion angle is located halfway between the trans and cis isomers. The reaction trajectory of IT bifurcates into two structurally distinct cis intermediates via hula-twist and bicycle-pedal pathways. The bifurcating reaction pathways can be controlled by weakening the hydrogen bond between the chromophore and an adjacent residue via E46Q mutation, which switches off the bicycle-pedal pathway.

Transient X‐ray Diffraction Reveals Global and Major Reaction Pathways for the Photolysis of Iodoform in Solution

The understanding of reaction mechanisms requires detailed information about the processes that take place during the reactions. Various time-resolved optical spectroscopic tools have been developed to track such processes, and reaction dynamics can now be routinely investigated, with a time resolution of tens of femtoseconds, by using these optical techniques. Typical information provided by timeresolved spectroscopy includes the time constants of reaction intermediates and limited structural information. In most cases, however, detailed structural information, such as the bond lengths and angles in reaction intermediates, are extremely difficult to obtain from time-resolved optical spectroscopy (except for a few favorable cases in which they can be deduced from time-resolved vibrational spectroscopy and multi-dimensional spectroscopy measurements). Replacing the optical probe pulses in time-resolved spectroscopy measurements with either electron or Xray pulses converts the optical resonances in energy space into atomic interferences in real space, which offers a complementary—and more direct—way to investigate the structural dynamics of molecular reactions. Because of the relatively low penetration depth of electrons, X-rays are more suitable for probing crystalline and liquid samples; for example, all the atoms in a protein can be tracked during its biological function by means of timeresolved X-ray crystallography, but to do so it is necessary to produce single protein crystals. This limitation has been recently overcome by introducing transient X-ray liquidography (TXL), a method through which the transient molecular structures present in a liquid sample can be captured in one dimension by performing time-resolved Xray diffraction measurements in the liquid phase. TXL is a new technique that can be used to investigate reactions in solution, where most of the chemically and biologically relevant processes take place. Since the diffraction patterns generated by the short X-ray pulses arriving at the sample after laser excitation include all the molecular structures present in the irradiated volume, the analysis of TXL data can reveal the structural evolution of all the reaction pathways in the sample (limited only by the signal-to-noise ratio of the diffracted difference signal). We recently succeeded in studying the structural reaction dynamics of several molecules in solution by using this method. The photochemistry of iodoform (CHI3) has received considerable attention because of the suggested formation of a unique intermediate, called isoiodoform (CHI2 I), which has been studied by using several time-resolved spectroscopic methods, such as transient absorption and transient resonance Raman spectroscopies. According to these studies, a parent iodoform molecule loses an iodine atom upon photoexcitation at 267 nm. The CHI2 radical and the I atom then recombine geminately to form isoiodoform within the solvent cage; this is a common reaction in diand trihaloalkanes. Previous studies suggest that isoiodoform is the major intermediate, with a lifetime of several microseconds. We note that optical spectroscopy can be highly sensitive to a particular species, but sometimes this advantage translates into biased or nonglobal sampling, that is, certain intermediates might be optically “silent” and escape detection. In contrast, the diffraction signal contains scattering information from all the atoms in the sample, thus providing a global picture of the reactions—although at the expense of sensitivity. Herein we report the global dynamics of the photodissociation of iodoform in methanol and show that the formation of the isomer is not a major reaction channel in the investigated time range, that is, from 100 ps to 3 ms. Time-resolved diffraction data were collected on the pump–probe beamline ID09B at the European Synchrotron Radiation Facility (ESRF) at time delays of 3 ns; 100, 100, and 300 ps; 1, 3, 6, 10, 30, 45, 60, 300, and 600 ns; and 1 and 3 ms. The diffraction signal corresponding the structural change is quite weak (about 0.1%) relative to the total diffraction signal. To extract the structural changes only, a non-excited reference data (at 3 ns) is subtracted from the diffraction data obtained at positive time delays. To magnify the scattered intensities at high angles (at which the signal becomes weak as a result of the decay in the atomic form factors), the change in the diffracted intensity, DS(q), is multiplied by q= (4p/l)sin(q/2), where l is the X-ray wave[*] J. H. Lee, J. Kim, K. H. Kim, Dr. J. Choi, Prof. H. Ihee Center for Time-Resolved Diffraction Department of Chemistry (BK21) Korea Advanced Institute of Science and Technology (KAIST) 335 Gwahangno, Yuseong-gu, Daejeon 305–701 (Republic of Korea) Fax: (+82)42-869-2810 E-mail: hyotcherl.ihee@kaist.ac.kr Homepage: http://time.kaist.ac.kr

Ultrafast X-ray Solution Scattering Reveals Different Reaction Pathways in the Photolysis of Triruthenium Dodecacarbonyl (Ru3(CO)12) after Ultraviolet and Visible Excitation

Ultrafast (ps) time-resolved X-ray scattering was used to study the structural dynamics of Ru(3)(CO)(12) in cyclohexane after photolysis at 260 nm. Two intermediates form after 100 ps at the onset of the reaction: Ru(3)(CO)(10) for the CO loss channel and Ru(3)(CO)(11)(mu-CO) for the metal-metal cleavage channel. In our previous study at 390 nm, by contrast, three intermediates were observed simultaneously at the onset of the reaction that all relax back to Ru(3)(CO)(12) with different lifetimes. The major difference between photolysis at 260 and 390 nm is that in the first case Ru(3)(CO)(10)(mu-CO) is formed by bimolecular recombination of Ru(3)(CO)(10) with a free CO in 50 ns, whereas in the second case it forms directly from Ru(3)(CO)(12) at the onset of the reaction. The differences between the photofragmentation pathways are related to the absorption bands available at the two wavelengths. The extrema in the difference radial distribution functions (RDFs) are unambiguously assigned by decomposing the total signal into contributions from the solutes, the solvent and the solute-solvent cross-terms, and also contributions from each candidate species. The difference RDFs reveal the depletion of Ru-Ru bonds (2.88 A) in the initial Ru(3)(CO)(12) molecule and formation of Ru(3)(CO)(10) as the major photoproduct. The high-resolution X-ray (88 keV) scattering pattern of pure liquid C(6)H(12) indicates that the solvent dynamics at early time delays is due to broadening of the intermolecular interatomic correlations at constant volume, whereas during thermal expansion at longer time delays, it results from shifts in these correlations.

Density functional theory assessment of molecular structures and energies of neutral and anionic Al(n) (n = 2-10) clusters.

We report the results of a benchmarking study on hybrid, hybrid-meta, long-range-corrected, meta-generalized gradient approximation (meta-GGA), and GGA density functional theory (DFT) methods for aluminum (Al) clusters. A range of DFT functionals, such as B3LYP, B1B95, PBE0, mPW1PW91, M06, M06-2X, ωB97X, ωB97XD, TPSSh, BLYP, PBE, mPWPW91, M06-L, and TPSS, have been used to optimize the molecular structures and calculate the vibrational frequencies and four energetic parameters for neutral and anionic Al(n) (n = 2-10) clusters. The performances of these functionals are assessed systematically by calculating the vertical ionization energy for neutral Al clusters and the vertical electron detachment energy for anionic Al clusters, along with the cohesive energy and dissociation energy. The results are compared with the available experimental and high-level ab initio calculated results. The calculated results showed that the PBE0 and mPW1PW91 functionals generally provide better results than the other functionals studied. TPSS can be a good choice for the calculations of very large Al clusters. On the other hand, the B3LYP, BLYP, and M06-L functionals are in poor agreement with the available experimental and theoretical results. The calculated results suggest that the hybrid DFT functionals like B3LYP do not always provide better performance than GGA functionals.

Spin-orbit density functional and ab initio study of HgXn (X=F, Cl, Br, and I; n=1, 2, and 4)

Quantum chemical calculations of HgX(n) (X=F, Cl, Br, and I; n=1, 2, and 4) in the gas phase are performed using the density functional theory (DFT), two-component spin-orbit (SO) DFT, and high-level ab initio method with relativistic effective core potentials (RECPs). Molecular geometries, vibrational frequencies, and various thermochemical energies are calculated and compared with available experimental results. We assess the performances of DFT functionals for calculating various molecular properties. The PBE0 functional is generally reasonable for the molecular geometries and the vibrational frequencies, but the M06 functional is more appropriate for estimating thermochemical energies. Both shape-consistent and energy-consistent RECPs correctly describe the SO effect.

Synthesis and electroluminescence properties of highly efficient dual core chromophores with side groups for blue emission

Highly efficient blue emitting materials consisting of dual core derivatives with phenyl and/or naphthyl side groups and asymmetric or symmetric structures were designed and synthesized. The asymmetric structures 1-naphthalen-1-yl-6-(10-phenyl-anthracen-9-yl)-pyrene (Ph-AP-Na) and 1-(10-naphthalen-1-yl-anthracen-9-yl)-6-phenyl-pyrene (Na-AP-Ph), and the symmetric structures 1-phenyl-6-(10-phenyl-anthracen-9-yl)-pyrene (Ph-AP-Ph) and 1-naphthalen-1-yl-6-(10-naphthalen-1-yl-anthracen-9-yl)-pyrene (Na-AP-Na) were synthesized. Of the synthesized compounds, Na-AP-Na was found to exhibit the highest EL device efficiency of 5.46 cd A−1. Ph-AP-Na, Na-AP-Ph, Ph-AP-Ph, and Na-AP-Na exhibit EL maximum values of real blue color in the range 455 nm to 463 nm. The y values of their color coordinates are within the range 0.125 to 0.142, so these compounds exhibit good blue color coordinates for displays. The lifetime of the Na-AP-Na device was more than three times longer than that of the AP dual core (1-anthracen-9-yl-pyrene) device.

Association between metabolic syndrome and serum leptin levels in postmenopausal women

Menopausal status is associated with weight gain, increased central fat mass, abnormal lipid metabolism, insulin resistance and susceptibility to metabolic syndrome (MetS). Leptin is synthesised and secreted by adipocytes. Serum leptin levels are highly correlated with fat mass. We determined the association between MetS and serum leptin levels in 153 postmenopausal women. The difference in serum leptin level between MetS and non-MetS groups showed a statistical significance after adjusting for body mass index (BMI; 19.9 ± 9.5 vs 12.1 ± 5.9 ng/ml, p = 0.013). The indicator of abdominal obesity, waist-to-hip ratio (WHR) and visceral fat area (VFA), had a positive correlation with serum leptin level in non-obese subjects after adjusting for BMI (p = 0.017, p < 0.001, respectively). Of the components of MetS, abdominal obesity and the number of MetS components had a positive correlation with serum leptin level (p < 0.05, p < 0.001, respectively).

Human rotavirus genotypes in hospitalized children, South Korea, April 2005 to March 2007.

Availability of new rotavirus vaccines highlights the need to maintain and enhance rotavirus strain surveillance. We collected stool samples from children with gastroenteritis admitted to eight hospitals in South Korea from April 2005 to March 2007. Of the 6057 samples collected, 1337 (22%) were positive for rotavirus by one of several antigen detection assays. G and P genotypes were identified for 1299 (97%) of rotavirus-positive specimens. G1P[8] (36%) was the most prevalent strain, followed by G3P[8] (16%), G4P[6] (8.9%) and G1P[6] (8.2%). G1P[8] was also the most prevalent strain in each hospital. Seasonal peaks of rotavirus infection were noted from November 2005 to April 2006 and January to March 2007. This large-scale surveillance study provides important insights into rotavirus genotype distribution and pattern changes in South Korea.

Structural Dynamics of 1,2-Diiodoethane in Cyclohexane Probed by Picosecond X-ray Liquidography

We investigate the structural dynamics of iodine elimination reaction of 1,2-diiodoethane (C(2)H(4)I(2)) in cyclohexane by applying time-resolved X-ray liquidography (TRXL). The TRXL technique combines structural sensitivity of X-ray diffraction and 100 ps time resolution of X-ray pulses from synchrotron and allows direct probing of transient structure of reacting molecules. From the analysis of time-dependent X-ray solution scattering patterns using global fitting based on DFT calculation and MD simulation, we elucidate the kinetics and structure of transient intermediates resulting from photodissociation of C(2)H(4)I(2). In particular, the effect of solvent on the reaction kinetics and pathways is examined by comparison with an earlier TRXL study on the same reaction in methanol. In cyclohexane, the C(2)H(4)I radical intermediate undergoes two branched reaction pathways, formation of C(2)H(4)I-I isomer and direct dissociation into C(2)H(4) and I, while only isomer formation occurs in methanol. Also, the C(2)H(4)I-I isomer has a shorter lifetime in cyclohexane by an order of magnitude than in methanol. The difference in the reaction dynamics in the two solvents is accounted for by the difference in solvent polarity. In addition, we determine that the C(2)H(4)I radical has a bridged structure, not a classical structure, in cyclohexane.

The Effects of Alcohol Abstinence on BDNF, Ghrelin, and Leptin Secretions in Alcohol‐Dependent Patients with Glucose Intolerance

BACKGROUND Alcohol use affecting the risk of type 2 diabetes mellitus (T2DM) is poorly identified as well as the role of brain-derived neurotrophic factor (BDNF), ghrelin, and leptin in alcohol dependence with T2DM. We tested the hypothesis that alcohol abstinence affects diabetes-related factors and BDNF, ghrelin, and leptin secretions in alcohol-dependent patients with glucose intolerance. METHODS A total of 64 male alcohol-dependent patients were classified into normal glucose tolerance (NGT), pre-diabetes mellitus (pre-DM), and diabetes mellitus (DM) groups according to a 75-g oral glucose tolerance test (OGTT). All participants got alcohol dependence rehabilitation treatment for 30 days, and then we compared changes in BDNF, ghrelin, and leptin between pre- and post-alcohol abstinence. RESULTS After alcohol abstinence, both pre-DM and DM groups had significantly decreased levels of fasting glucose. All 3 groups exhibited elevated ghrelin levels and reduced leptin levels, but BDNF levels were significantly increased only in the pre-DM group. The pre-DM group had large increases in BDNF and ghrelin levels compared with those of the NGT group. Moreover, decreases in homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose, and leptin levels in the DM group were larger than those in the NGT group. CONCLUSIONS Alcohol abstinence might influence diabetes-related factors of alcohol-dependent patients with glucose intolerance. Further, BDNF, ghrelin, and leptin differently affect this improvement, depending on the stage of DM. In the pre-DM group, elevated BDNF and ghrelin levels are likely to influence insulin sensitivity, insulin resistance, and fasting glucose levels. Further, reduced leptin levels after abstinence might be related to improved glucose kinetics in patients with diabetes.