Chemi- and Bioluminescence of Cyclic Peroxides.

Bioluminescence is a phenomenon that has fascinated mankind for centuries. Today the phenomenon and its sibling, chemiluminescence, have impacted society with a number of useful applications in fields like analytical chemistry and medicine, just to mention two. In this review, a molecular-orbital perspective is adopted to explain the chemistry behind chemiexcitation in both chemi- and bioluminescence. First, the uncatalyzed thermal dissociation of 1,2-dioxetane is presented and analyzed to explain, for example, the preference for triplet excited product states and increased yield with larger nonreactive substituents. The catalyzed fragmentation reaction and related details are then exemplified with substituted 1,2-dioxetanone species. In particular, the preference for singlet excited product states in that case is explained. The review also examines the diversity of specific solutions both in Nature and in artificial systems and the difficulties in identifying the emitting species and unraveling the color modulation process. The related subject of excited-state chemistry without light absorption is finally discussed. The content of this review should be an inspiration to human design of new molecular systems expressing unique light-emitting properties. An appendix describing the state-of-the-art experimental and theoretical methods used to study the phenomena serves as a complement.

Benchmark study of popular density functionals for calculating binding energies of three-center two-electron bonds.

Density functional theory (DFT) can be used to study the three-center two-electron (3c2e) bonding mode, which is universal in catalysts containing alkaline-earth (Ae) and boron-group (Bg) elements. However, because of the delocalization pattern of the 3c2e bond, the wavefunction cannot be accurately described by DFT methods. The calculated energies of Ae and Bg catalysts therefore fluctuate greatly when different functionals are used, largely because of inconsistent DFT-calculated binding energies of 3c2e bonds. Nevertheless, with the development of supercomputers and theoretical calculation software, the DFT method is becoming increasingly popular for studying Ae and Bg catalysts. In this study, we compared the performances of 21 functionals with the high-level composite G3B3 method in calculations for the binding energies of 3c2e bonds. Several frequently used post-Hartree-Fock methods were also tested. The calculation results indicate that the M06-2X, MN12-L, and MN15 functionals give consistent and reliable binding energies for common 3c2e bonds. © 2018 Wiley Periodicals, Inc.

Tuning the fluorescence of calcium-discharged photoprotein obelin via mutating at the His22-Phe88-Trp92 triad - a QM/MM study.

The fluorescence (FL) of calcium-discharged photoprotein (CaDP) can be altered by easily mutating CaDP without modifying coelenteramide (CLM), which is the decarboxylation product of coelenterazine in calcium-regulated photoprotein. The His22-Phe88-Trp92 triad (the ordering numbers of three amino acids are sorted by a crystal structure (PDB: 2F8P) of calcium-discharged obelin, i.e., CaDP-obelin) is closely related to CaDP-obelin FL, since it exists in close proximity to the 5-p-hydroxyphenyl of CLM. Therefore, it is important to thoroughly investigate how the mutations of this triad affect the emission color of CaDP-obelin FL. In this study, by mutating wild-type CaDP-obelin (WT) at the His22-Phe88-Trp92 triad, we theoretically constructed its nine mutants of separable FL colors. Through combined quantum mechanics and molecular mechanics (QM/MM) calculations and molecular dynamics (MD) simulations, the influence of the mutations of this triad on the CaDP-obelin FL was analyzed considering the H-bond effect and the charge effect. This study demonstrated that the mutations at the His22-Phe88-Trp92 triad redistribute the charges on the D-π-A molecule, CLM, change the charge transfer from the D to the (π + A) moiety, and thereby alter the FL emission. Appending more negative charges on the phenolate moiety of CLM benefits the FL redshift.

Bioluminescence of Firefly Squid via Mechanism of Single Electron-Transfer Oxygenation and Charge-Transfer-Induced Luminescence.

Watasenia scintillans (W. scintillans) is a deep-sea luminescent squid with a popular name of firefly squid. It produces flashes of blue light via a series of complicated luciferin-luciferase reactions involving ATP, Mg2+, and molecular oxygen. Tsuji has proposed a hypothetical scheme for this mysterious bioluminescence (BL) process, but the proposal is short of strong evidence experimentally or theoretically, especially for two key steps. They are the addition of molecular oxygen to luciferin and the formation of light emitter. For the first time, the present study investigates the two steps by reliable density functional theory (DFT) and time-dependent DFT. The results of calculated energetics, charge transfer process, electronic structures, and molecular dynamics give convincing support for Tsuji's proposal. The oxygenation reaction occurs with a single electron-transfer (SET) mechanism, and the light emitter is produced via the mechanism of gradually reversible charge-transfer-induced luminescence (GRCTIL). The simulation of nonadiabatic molecular dynamics further confirms the GRCTIL mechanisms and evaluates the quantum yield of the light emitter to be 43%. The knowledge obtained in the current study will help to understand a large amount of BL systems in nature, since the core structure of W. scintillans luciferin, imidazopyrazinone, is common in the luciferins of about eight phyla of luminescent organisms.

Intermolecular copigmentation between five common 3-O-monoglucosidic anthocyanins and three phenolics in red wine model solutions: The influence of substituent pattern of anthocyanin B ring.

In this study, intermolecular copigmentation between five primary wine monoglucosidic anthocyanins (cyanidin-3-O-glucoside, peonidin-3-O-glucoside, delphinidin-3-O-glucoside, petunidin-3-O-glucoside, and malvidin-3-O-glucoside) and three common wine phenolics (gallic acid, (-)-epicatechin, and quercetin-3-O-glucoside) were investigated through experimental and theoretical methods, and the influence of substituent pattern of anthocyanin B ring was studied emphatically. Chromatic and thermodynamic analysis showed there were great differences among these different pigment-copigment systems. Spatial conformations of the 15 copigmentation complexes were obtained through theoretical calculation, and diverse π-π stacking modes were observed. These results indicated that the substituent pattern of anthocyanin B ring had significant impact on its affinity to copigments, and more, the structures of pigments and copigments determined the color expression and stability of copigmentation together.

Luminescence Activity Decreases When v-coelenterazine Replaces Coelenterazine in Calcium-Regulated Photoprotein-A Theoretical and Experimental Study.

Calcium-regulated photoproteins are found in at least five phyla of organisms. The light emitted by those photoproteins can be tuned by mutating the photoprotein and/or by modifying the substrate coelenterazine (CTZ). Thirty years ago, Shimomura observed that the luminescence activity of aequorin was dramatically reduced when the substrate CTZ was replaced by its analog v-CTZ. The latter is formed by adding a phenyl ring to the π-conjugated moiety of CTZ. The decrease in luminescence activity has not been understood until now. In this paper, through combined quantum mechanics and molecular mechanics calculations as well as molecular dynamics simulations, we discovered the reason for this observation. Modification of the substrate changes the conformation of nearby aromatic residues and enhances the π-π stacking interactions between the conjugated moiety of v-CTZ and the residues, which weakens the charge transfer to form light emitter and leads to a lower luminescence activity. The microenvironments of CTZ in obelin and in aequorin are very similar, so we predicted that the luminescence activity of obelin will also dramatically decrease when CTZ is replaced by v-CTZ. This prediction has received strong evidence from currently theoretical calculations and has been verified by experiments.

Mechanistic insight into marine bioluminescence: photochemistry of the chemiexcited Cypridina (sea firefly) lumophore.

Cypridina hilgendorfii (sea firefly) is a bioluminescent crustacean whose bioluminescence (BL) reaction is archetypal for a number of marine organisms, notably other bioluminescent crustaceans and coelenterates. Unraveling the mechanism of its BL is paramount for future applications of its strongly emissive lumophore. Cypridina produces light in a three-step reaction: First, the cypridinid luciferin is activated by an enzyme to produce a peroxide intermediate, cypridinid dioxetanone (CDO), which then decomposes to generate excited oxyluciferin (OxyCLnH*). Finally, OxyCLnH* deexcites to its ground state along with emission of bright blue light. Unfortunately, the detailed mechanism of the critical step, the thermolysis of CDO, remains unknown, and it is unclear whether the light emitter is generated from a neutral form (CDOH) or anionic form (CDO(-)) of the CDO precursor. In this work, we investigated the key step in the process by modeling the thermal decompositions of both CDOH and CDO(-). The calculated results indicate that the decomposition of CDO(-) occurs via the gradually reversible charge transfer (CT)-initiated luminescence (GRCTIL) mechanism, whereas CDOH decomposes through an entropic trapping mechanism without an obvious CT process. The thermolysis of CDO(-) is sensitive to solvent effects and is energetically favorable in polar environments compared with the thermolysis of CDOH. The thermolysis of CDO(-) produces the excited oxyluciferin anion (OxyCLn(-)*), which combines with a proton from the environment to form OxyCLnH*, the actual light emitter for the natural system.

Resection is an effective treatment for recurrent follicular dendritic cell sarcoma from retroperitoneum: unusual presentation of a rare tumor.

Retroperitoneum follicular dendritic cell sarcoma (FDCS) is an extremely rare neoplasm. The treatment of this disease is not clear. A 49-year-old Chinese female who had been found a 4.4×4 cm retroperitoneum mass by routine physical examination was received radical resection. Pathology revealed an inflammatory pseudotumor-like follicular dendritic cell tumor. After five years follow-up, a new nodule was noted on the tail of pancreas by routine CT evaluation. Re-resection was performed and pathological examination found a spindle-cell tumor with a great quantity of froth histiocytes. Immunohistochemical stains were positive for CD35 and CD21 which suggested it was a recurrent FDCS. Retroperitoneum FDCS is a very rare tumor. Surgical resection may be the first choice for this disease, even for recurrent tumor, if feasible. A relatively good prognosis often is achieved when compared with other malignancy.

PU.1-silenced dendritic cells prolong allograft survival in rats receiving intestinal transplantation.

AIM: To investigate the function of PU.1-silenced semi-mature dendritic cells (DCs) and the possibility of utilizing cell immunity in rat intestinal transplantation. METHODS: DCs were isolated from the bone marrow of F344 rats and cultured using the adherent method. The PU.1 gene was knocked down in DCs using small interfering RNAs (siRNAs) for 24 h, and the cells were then incubated with lipopolysaccharide for 48 h. The PU.1 siRNA that had the highest silencing efficiency was screened using reverse transcription-polymerase chain reaction and Western blot for further study. The tolerance capacity was analyzed and compared between PU.1-silenced DCs (siRNA PU.1 group), negative control-silenced DCs (siRNA NC group) and immature DCs (control group) both in vitro and in vivo. RESULTS: Blocking expression of the PU.1 gene in vitro led to a reduction in DC maturation and an increased tolerance capability. PU.1-silenced DCs expressed moderate levels of major histocompatibility complex (MHC)-II and low levels of co-stimulatory molecules, and produced more interleukin (IL)-10, but less IL-12. Compared with the negative control group, surface molecules cluster of differentiation 80 (CD80), CD86 and MHC-II in the siRNA PU.1 group were 27.0% ± 5.6%, 23.6% ± 4.8% and 36.8% ± 6.8%, respectively, and showed a significantly lower trend (P < 0.05). In vivo treatment of recipients with PU.1-silenced DCs injected before intestinal transplantation (siRNA PU.1 group), significantly prolonged allograft survival and resulted in better tissue histopathology compared with the siRNA NC group and control group. Mean survival time after transplantation was 14.3 ± 3.3 d in the siRNA PU.1 group (P < 0.05). CONCLUSION: PU.1-silenced semi-mature DCs induced partial immune tolerance both in vitro and in vivo, which could be used as a new strategy to promote transplantation tolerance.