Photoelectron spectra and structures of three cyclic dipeptides: PhePhe, TyrPro, and HisGly

We have investigated the electronic structure of three cyclic dipeptides: cyclo(Histidyl-Glycyl) (cHisGly), cyclo(Tyrosyl-Prolyl) (cTyrPro), and cyclo(Phenylalanyl-Phenylalanyl) (cPhePhe) in the vapor phase, by means of photoemission spectroscopy and theoretical modeling. The last compound was evaporated from the solid linear dipeptide, but cyclised, losing water to form cPhePhe in the gas phase. The results are compared with our previous studies of three other cyclopeptides. Experimental valence and core level spectra have been interpreted in the light of calculations to identify the basic chemical properties associated with the central diketopiperazine ring, and with the additional functional groups. The valence spectra are generally characterized by a restricted set of outer valence orbitals separated by a gap from most other valence orbitals. The theoretically simulated core and valence spectra of all three cyclic dipeptides agree reasonably well with the experimental spectra. The central ring and the side chains act as independent chromophores whose spectra do not influence one another, except for prolyl dipeptides, where the pyrrole ring is fused with the central ring. In this case, significant changes in the valence and core level spectra were observed, and explained by stronger hybridization of the valence orbitals.     

Synthesis and Structure of [Fe(TPA)Cl2](ClO4) and [{Fe(TPA)Cl}2O](ClO4)2 Where TPA = Tris-(2-pyridylmethyl)amine

Journal of Chemical Crystallography - [Fe(TPA)Cl2](ClO4), where TPA is tris-(2-pyridylmethyl)amine, crystallizes in the orthorhombic space group P212121 with Z?=?4,...     

Imaging of photodynamically generated singlet oxygen luminescence in vivo

We describe a novel scanning-laser system for imaging type-II photodynamically generated singlet oxygen (1O2[1delta(g)]) luminescence and demonstrate it in vivo in an intradermal tumor model in mice. We verify the strong oxygen-dependence of the signal and show that the images are near the practical resolution limit.     

A quantum mechanical study of bioactive 3-chloro-2,5-dihydroxybenzyl alcohol through substitutions

Electronic structures, vibrational and ionization spectra of 3-chloro-2,5-dihydroxybenzyl alcohol (CHBA), a novel bioactive benzene derivative from marine fungi, are presented in this study using quantum mechanical methods such as density functional theory and outer valence Green function method. A number of related benzene derivatives such as chlorobenzene, 3-chlorobenzyl alcohol, hydroquinone and chlorohydroquinone are also studied, in order to assist our understanding of the structure, properties and interactions of CHBA. Vibrational spectra such as infrared (IR) and Raman spectra reveal signatures of the functional group substitutions and their hydrogen bond interactions in CHBA. Solvent effects on the IR spectra of CHBA with polar and non-polar solvents are simulated using the polarizable continuum model (PCM) and cause redshifts of some of the IR spectral frequencies with respect to the gas phase values at both ends of the 400?C4,000?cm^?1 region. The inner-shell ionization spectra, in particular the C?CK spectra of the benzene derivatives, reveal detailed chemical environmental changes of the carbon and oxygen atoms due to the substitutions. The valence ionization energies of the highest occupied molecular orbital (HOMO) and the 3rd HOMO, (HOMO-2) of the benzene derivatives respond significantly to the substitutions, whereas the charge distributions of the HOMO and 2nd HOMO (HOMO-1) do not change significantly from their benzene counterparts. As a result, the 3rd HOMO changes significantly in both ionization energies and the charge distributions, which can serve as a signature of the substitutions among the benzene derivatives.     

Valence structures of aromatic bioactive compounds: a combined theoretical and experimental study

Valence electronic structures of three recently isolated aryl bioactive compounds, namely 2‐phenylethanol (2PE), p‐hydroxyphenylethanol (HPE) and 4‐hydroxybenzaldehyde (HBA), are studied using a combined theoretical and experimental method. Density functional theory‐based calculations indicate that the side chains cause electron charge redistribution and therefore influence the aromaticity of the benzene derivatives. The simulated IR spectra further reveal features induced by the side chains. Solvent effects on the IR spectra are simulated using the polarizable continuum model, which exhibits enhancement of the O—H stretch vibrations with significant red‐shift of 464 cm^?1 in 2PE. A significant spectral peak splitting of 94 cm^?1 between O(4)—H and O(8)—H of HPE is revealed in an aqueous environment. Experimental measurements for valence binding energy spectra for 2PE, HPE and HBA are presented and analyzed using outer‐valence Green function calculations. The experimental (predicted) first ionization energies are measured as 9.19 (8.79), 8.47 (8.27) and 8.97 (8.82) eV for 2PE, HPE and HBA, respectively. The frontier orbitals (highest occupied molecular orbitals, HOMOs, and lowest unoccupied molecular orbitals, LUMOs) have similar atomic orbital characters although the HOMO–LUMO energy gaps are quite different.     

Correlation of electronic structures of three cyclic dipeptides with their photoemission spectra

We have investigated the electronic structure of three cyclic dipeptides: cyclo(Glycyl-Glycyl) (cGG), cyclo(Leucyl-Prolyl) (cLP), and cyclo(Phenylalanyl-Prolyl) (cPP). These compounds are biologically active and cLP and cPP are derived from cGG (also known as diketopiperazine), by the addition of the respective functional groups of the amino acids, namely, phenyl, alkyl or a fused pyrrolidine ring (proline). Experimental valence and core level spectra have been interpreted in the light of theoretical calculations to identify the basic chemical properties associated with the central ring, and with the additional functional groups in cLP and cPP. The theoretically simulated spectra of all three cyclic dipeptides in both valence and core spaces agreed reasonably well with the experimental spectra. The three molecules displayed similarities in their core spectra, suggesting that the diketopiperazine structure plays an important role in determining the inner shell spectrum. The experimental C 1s spectra of cLP and cPP are analogous but differ from cGG due to the side chains attached to the diketopiperazine structure. Single spectral peaks in the N 1s (and O 1s) spectra of the dipeptides indicate that the chemical environment of the nitrogen atoms (and oxygen atoms) are very similar, although they show a small splitting in the simulated spectra of cPL and cPP, due to the reduction of their point group symmetry. Valence band spectra of the three dipeptides in the frontier orbital region of 9-11 eV exhibit similarities; however theoretical analysis shows that significant changes occur due to the involvement of the side chain in the frontier orbitals of cPP, while lesser changes are found for cLP.     

Combination of 5-Fluorouracil with Photodynamic Therapy: Enhancement of Innate and Adaptive Immune Responses in a Murine Model of Actinic Keratosis†

We previously showed that a combination of differentiation-inducing agents (5-fluorouracil [5FU], vitamin D3 or methotrexate) and aminolevulinate-based photodynamic therapy (PDT) improves clinical responses by enhancing protoporphyrin IX (PpIX) photosensitizer levels and cell death. Here, we show that in addition to its previously known effects, 5FU enhances PDT-induced tumor-regressing immunity. Murine actinic keratoses were treated with topical 5FU or vehicle for 3 days prior to aminolevulinic acid application, followed by blue light illumination (~417 nm). Lesions were harvested for time-course analyses of innate immune cell recruitment into lesions, i.e. neutrophils (Ly6G+) and macrophages (F4/80+), which peaked at 72 h and 1 week post-PDT, respectively, and were greater in 5FU-treated lesions. Enhanced infiltration of activated T cells (CD3+) throughout the time course, and of cytotoxic T cells (CD8+) at 1–2 weeks post-PDT, also occurred in 5FU-treated lesions. 5FU pretreatment reduced the presence of cells expressing the immune checkpoint marker PD-1 at ~72 h post-PDT, favoring cytotoxic T cell activity. A combination of 5FU and PDT, each individually known to induce long-term tumor-targeting immune responses in addition to their more immediate effects on cancer cells, may synergize to provide better management of squamous precancers.