There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

https://zenodo.org/record/1258475/files/article.pdf

Electron transfers in chemistry and biology

Signaling Recognition Events with Fluorescent Sensors and Switches.

Photodynamic therapy involves administration of a tumor-localizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (Photofrin) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered.

Photodynamic Therapy

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Aryl-aryl bond formation one century after the discovery of the Ullmann reaction.

On the basis of a fundamental property of nanoparticles, the self-assembling at a liquid−liquid interface to form “colloidosomes”, a heterogeneous reaction takes place on the exposed surface of the nanoparticles to produce the heterodimers of two distinct nanospheres, which can be modified by two different functional molecules in a particle-specific manner.

Heterodimers of nanoparticles: Formation at a liquid-liquid interface and particle-specific surface modification by functional molecules

A challenge in chemistry is an artificial enzyme that mimics the functions of the natural system but is simpler than proteins. The intensive development of artificial enzymes that use a variety of matrices, the rapid progress in supramolecular gels, and the apparent “superactivity” exhibited by supramolecular hydrogel-immobilized enzymes, prompted us to evaluate whether supramolecular hydrogels will improve the activity of artificial enzymes for catalyzing reactions in water or in organic media. To demonstrate the concept, we used hemin as the prosthetic group to mimic peroxidase, a ubiquitous enzyme that catalyzes the oxidation of a broad range of organic and inorganic substrates by hydrogen peroxide or organic peroxides. The structures of the active site as well as the reaction mechanism of peroxidases are well studied. Much effort has been focused on incorporating metalloporphyrins into protein-like scaffolds in the quest towards peroxidase mimetics, which do not show satisfactory activity and selectivity mainly owing to the lack of the peptidic microenvironment that exists in the native peroxidase. The shape of the protein pocket and the amino acid residues or functional groups that surround the active site bring about the special inclusion behavior between the enzyme and the substrate. As a result, b-cyclodextrins (bCDs), which are a frequently used model system, act as an excellent enzyme model owing to their appropriate size and their fairly rigid and hydrophobic cavities that provide favorable binding of the prosthetic group as well as substrates. Experimentally, b-CD-modified hemins have showed higher activity relative to free hemin, suggesting that supramolecular hydrogels may act as an alternative matrix to encapsulate hemin for the mimetic of peroxidase. Supramolecular hydrogels, formed by the self-assembly of nanofibers of amphiphilic oligopeptides or small molecules, have served as scaffolds for tissue engineering, a medium for screening inhibitors of enzymes, 14] a matrix for biomineralization, and as biomaterials for wound healing. The application of supramolecular hydrogels as the skeletons of artificial enzymes has yet to be explored. Similar to peptide chains that form active sites in enzymes, the selfassembled nanofibers of amino acids in the supramolecular hydrogels could act as the matrices of artificial enzymes. Thus, the supramolecular-hydrogel systems serve two functions: 1) as the skeletons of the artificial enzyme to aid the function of the active site (e.g., hemin) and, 2) as the immobilization carriers to facilitate the recovery of the catalysts in practical applications. Herein, we mixed hemin chloride (3) into the hydrogel formed by the self-assembly of two simple derivatives of amino acids (1 and 2). The activity of this new type of artificial enzyme is higher than the activity of free hemin, hemin in bCD, or hemin in polymeric hydrogels. This artificial enzyme shows the highest activity in toluene for an oxidation reaction, reaching about 60% of the nascent activity of horseradish peroxidase (HRP). This result is particularly interesting because it implies that the control of the structure of hydrogelators could tailor the nanofibers as an adjustable microenvironment around active centers and thereby affect the performance of artificial enzymes. Moreover, the supramolecular hydrogel acts as an effective carrier to minimize the dimerization and oxidative degradation of free hemin in the peroxidization reaction. Overall, the supramolecular-hydrogel-based artificial enzyme offers a new opportunity to achieve catalysis with high operational stability and reusability, which ultimately would benefit industrial biotransformation. Scheme 1 illustrates the simple procedure of using supramolecular hydrogels to encapsulate hemin. Equal molar equivalents of 1 and 2 and two equivalents of Na2CO3 in water formed a suspension, which turned into a clear solution at about 60 8C. Then, 3 was added and dissolved immediately in the solution. The subsequent cooling of the solution to room temperature afforded a supramolecular hydrogel containing hemin molecules (Gel II). Without the addition of 3, the same procedure gave the control (Gel I). As a point of reference, we made the artificial peroxidases by using b-CD or a polyacrylamide hydrogel to encapsulate hemin according to the literatures. As shown in the TEM and AFM images in Figure 1, Gel I and Gel II have different morphologies. The networks of Gel I have 50–500-nm pores formed by the nanofibers (roughly 20 nm in diameter) of the self-assembled 1 and 2. Besides the relatively large pores, the TEM image of the nanofibers in Gel II, however, shows two distinct regions: the dark part (fibers of approximately 20 nm in diameter) and the gray part (surface layer of approximately 6 nm thickness). [*] Dr. Q. Wang, Dr. Z. Yang, Prof. C. K. Chang, Prof. B. Xu Department of Chemistry The Hong Kong University of Science and Technology Clear Water Bay, Hong Kong (P.R. China) Fax: (+852)2358-1594 E-mail: chang@ust.hk chbingxu@ust.hk

A Supramolecular-Hydrogel-Encapsulated Hemin as an Artificial Enzyme to Mimic Peroxidase**

Rapid initiation of apoptosis can be induced by photodynamic therapy, depending on the cell line and sensitizer employed. In this study, we evaluated the photodynamic responses to two structurally related photosensitizing agents, using the P388 murine leukemia cell line in culture. Photodamage mediated by tin etiopurpurin involved lysosomes and mitochondria and yielded a rapid apoptotic response; apoptotic nuclei were observed within 60 min after PDT. A drug analog, tin octaethylpurpurin amidine, targeted lysosomes, mitochondria and cell membranes; apoptotic nuclei were not observed until 24 h after PDT. These results, together with other recent reports, are consistent with the hypothesis that membrane photodamage can delay or prevent an apoptotic response to PDT.

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The role of subcellular localization in initiation of apoptosis by photodynamic therapy.

Photoinduced electron transfer mediated by a hydrogen-bonded interface

— Photodynamic therapy (PDT) of neoplastic cell lines is sometimes associated with the rapid initiation of apoptosis, a mode of cell death that results in a distinct pattern of cellular and DNA fragmentation. The apoptotic response appears to be a function of both the sensitizer and the cell line. In this study, we examined photodynamic effects of several photosensitizers on murine leukemia P388 cells. Two drugs, a porphycene dimer (PcD) and tin etiopurpurin (SnET2), which localized at lysosomal sites, were tested at PDT doses that resulted in 50% loss of viability (LD50), measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. An oligonucleosomal pattern of DNA degradation was observed within 1 h after irradiation. Neither sensitizer antagonized PDT-mediated internucleosomal DNA cleavage by the other. Very high PDT doses with either agent abolished this rapid internucleosomal cleavage. Exposure of cells to high concentrations of either sensitizer in the dark also resulted in rapid DNA fragmentation to nucle-osomes and nucleosome multimers; this effect was not altered by the antioxidant 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylic acid (trolox), although the latter could protect cells from cytotoxicity and apoptotic effects caused by LD50 PDT doses. Photodamage from two cat-ionic sensitizers, which localized at membrane sites, caused rapid DNA cleavage to 50 kb particles; however, no further fragmentation was detected after 1 h under LD10, LD50 or LD95 PDT conditions. Moreover, the presence of either cationic sensitizer inhibited the rapid internucleosomal cleavage induced by SnET2 or PcD photodamage. The site of photodynamic action may therefore be a major determinant of the initiation and rate of progression of apoptosis.

Chi K. Chang

Papers

Heterodimers of nanoparticles: Formation at a liquid-liquid interface and particle-specific surface modification by functional molecules

A Supramolecular-Hydrogel-Encapsulated Hemin as an Artificial Enzyme to Mimic Peroxidase**

The role of subcellular localization in initiation of apoptosis by photodynamic therapy.

Photoinduced electron transfer mediated by a hydrogen-bonded interface

Rapid Initiation of Apoptosis by Photodynamic Therapy