type-II Reactions Research Articles

Molecular Engineering of Pure Superoxide Radical Photogenerator for Hypoxia-Tolerant Tumor Theranostics.

Photodynamic therapy (PDT) is a promising cancer treatment, but limited oxygen supply in tumors (hypoxia) can hinder its effectiveness. This is because traditional PDT relies on Type-II reactions that require oxygen. Type-I photosensitizers (PSs) offer a promising approach to overcome the limitations of tumor photodynamic therapy (PDT) in hypoxic environments. To leverage the advantages of Type-I PDT, the design and evaluation of a series of Type-I PSs for developing pure Type-1 PSs, by incorporating benzene, thiophene, or bithiophene into the donor-acceptor molecular skeleton are reported. Among them, CTTI (with bithiophene) shows the best performance, generating the most superoxide radical (O2 •-) upon light irradiation. Importantly, CTTI exclusively produced superoxide radicals, avoiding the less effective Type-II pathway. This efficiency is due to CTTI's energy gap and low reduction potential, which favor electron transfer to oxygen for O2 •- generation. Finally, CTTI NPs are successfully fabricated by encapsulating CTTI into liposomes, and validated to be effective in killing tumor cells, even under hypoxic conditions, making them promising hypoxia-tolerant tumor phototheranostic agents in both in vitro and in vivo applications.

Primary reaction intermediates of Type-I photosensitized lipid oxidation as revealed by time-resolved optical spectroscopies

Chlorophyll a (Chl a) as a lipophilic photosensitizer can induce biomembrane destruction via Type-II reaction involving singlet oxygen (1O2) as a primary initiator. Type-I oxidation by an excited-state photosensitizer reacting directly with lipid substrate also contributes but the primary intermediate remains to be verified experimentally. We have investigated the reaction dynamics initiated by Chl a-photosensitization involving oxygen and the -C=C- moieties of lipids in the membranes of small unilamellar vesicles (SUVs) prepared from phospholipids of different degree of unsaturation (0, 1 or 2). Under anaerobic condition, femtosecond time resolved absorption (fs-TA) combined with spectroelectrochemical spectroscopies validated the formation of Chl a− in subpicoseconds, and time resolved fluorescence spectroscopy revealed the rapid quenching of 1Chl a* with a rate constant of (28 ns)−1. These ultrafast processes, independent of oxygen, are ascribed to the electron transfer reaction from a -C=C- moiety to 1Chl a* as an initiation step of Type-I reaction. On longer timescales, ns-TA spectroscopy unraveled the drastic quenching of 3Chl a* by either -C=C- or O2, and the quenching by O2 was found to be 20 times more efficient. This together with the 1O2-luminesence analysis prove the involvement of both types of photosensitization. In addition, HPLC-MS spectroscopy confirmed the ketonic, the alcoholic and the core-aldehyde products of lipid oxidation. Moreover, the oxygen dependent partition between Type-I and Type-II reactions is discussed on a detailed kinetics basis, showing that the two mechanisms of lipid oxidation are equally important under an oxygen concentration of 1.3×10−5 M at room temperature.

A clinical study of new cases of Hansen’s disease at a tertiary health care centre in post elimination era

<p><strong>Background</strong>: Leprosy, in 2016, globally a total of 214,783 new cases were reported over half of them were from India (135,485) alone. However, 16 other countries with pockets of high endemicity were reported. On the other hand, actual numbers of people affected by the disease is likely to be far higher than statistics show as there still prevails lack of awareness about the disease, lack of skills of general health staff in leprosy diagnosis, inadequate active case findings, lack of inclusion of cases from private sector and presence of high stigma in the community. Aims and objectives were to study the number of increasing new cases of Hansen’s disease in post elimination era.</p><p><strong>Methods</strong><strong>:</strong> A prospective observational study of number of new cases of leprosy presented at a department of DVL, BMCH, Chitradurga, Karnataka, from 2017 April-2018 September. A total of 91 cases were detected.</p><p><strong>Results:</strong> Series of 91 cases were detected, and based on WHO classification were classified as multibacillary (MB)-72 cases and paucibacillary (PB)-19 cases. The maximum number of cases were detected between 20-29 years of age. The male to female ratio was 1.2:1. 46 (50.54%) cases were diagnosed to have borderline tuberculoid (BT). Patients mainly belonged to low socioeconomic status (89.1%). Deformities were seen in 21 (23.07%)) cases. 7 patients presented with type-I reaction and 13 patients with type-II reactions.</p><p><strong>Conclusions:</strong> Even with MB-MDT and monitoring, some high endemic pockets of leprosy may continue to persists in India. Every year new cases are increasing and causing morbidity from neglected cases. We should not be complacent at this stage because it may become a serious health problem again.</p>

Electrophysiological Study of Nerves in Type-II Reaction in Leprosy.

Background:Leprosy is a chronic granulomatous infection primarily affecting the peripheral nervous system, skin and reticuloendothelial system. Cutaneous nerves are severely affected in lepra reaction and this leads to morbidity.Objective:To study electrophysiological pattern of different nerves involved in Type-II reactions in leprosy.Method:The present study was undertaken in 21 leprosy patients with Type-II reactions attending in and out-patient department of Dermatology & Venereology, B.R.D. Medical College, Gorakhpur from July 2005 to October 2006. This was a prospective case control study in which 20 healthy, age and sex matched people with no evidence of any disease (particularly nerve involvement) were included.Limitation:Lesser number of cases were studied.Result:The proximal motor conduction latency was significantly prolonged in both ulnar and common peroneal nerve and proximal motor conduction velocity was also significantly reduced. On examining the values beyond 2S.D. of the control value, distal latency was not affected and only proximal conduction was affected in ulnar nerve.Conclusion:In Type II lepra reaction the motor conduction abnormalities are not prominent. Abnormalities are relatively more marked in the proximal segment.

How the contagion at links influences epidemic spreading

The reaction-diffusion (RD) model of epidemic spreading generally assume that contagion occurs only at the nodes of network, i.e., the links are used only for migration/diffusion of agents. However, in reality, we observe that contagion occurs also among the travelers staying in the same car, train or plane etc., which consist of the links of network. To reflect the contagious effect of links, we here present a traveling-contagion model where contagion occurs not only at nodes but also at links. Considering that the population density in transportation is generally much larger than that in districts, we introduce different infection rates for the nodes and links, respectively, whose two extreme cases correspond to the type-I and type-II reactions in the RD model [V. Colizza, R. Pastor-Satorras, A. Vespignani, Nat. Phys. 3, 276 (2007)]. Through studying three typical diffusion processes, we reveal both numerically and theoretically that the contagion at links can accelerate significantly the epidemic spreading. This finding is helpful in designing the controlling strategies of epidemic spreading.

Reactive oxygen species from type-I photosensitized reactions contribute to the light-induced wilting of dark-grown pea (Pisum sativum) epicotyls.

Type-II, singlet oxygen-mediated photosensitized damage has already been shown to occur in epicotyls of dark-germinated pea (Pisum sativum L.) seedlings upon illumination, resulting in fast turgor loss and wilting. In this study we show evidence that the palette of reactive oxygen species (ROS) is more complex. Hydrogen peroxide, superoxide and hydroxyl radicals are also formed, suggesting the occurrence of type-I reactions as well. Moreover, hydrogen peroxide injection into the epicotyls in the dark was able to provoke wilting directly. Formation of hydroxyl radicals could also be triggered by the addition of hydrogen peroxide in the dark, preferentially in the mid-sections where wilting occurs, showing that potential mediators of a Fenton reaction are present in the epicotyls, but unevenly distributed. Localization of light-inducible ROS formation fully (hydrogen peroxide) or partially (superoxide radicals) overlaps with the distribution of monomer protochlorophyllide complexes, showing that these pigment forms are capable of provoking both type-I and type-II reactions.

Photo-transformations of 6-chloro-3-propargyloxy-2-aryl-4-oxo-4 H-1-benzopyran: 1,4-hydrogen abstraction in propargylethers

1,4-Biradicals generated in the Norrish type-II reactions of 3-propargyloxy-2-arylchromones lead to cyclic products involving the 2-aryl group. The formation and distribution of products varied with the nature of 2-aryl group.

Effect of hetero atom on the conformational stability of the forming ring in the transition structures of Type-II ene cyclization: a theoretical study

The chair conformation of the forming ring in the transition structure, for its high stability, is usually considered for the determination of the overall stereoselectivity in a type-II ene cyclization reaction. However, present theoretical investigation reveals that the presence of a heteroatom like oxygen or nitrogen in the tether of type-II carbonyl ene cyclization stabilizes the transition structure, in which the forming ring adopts a boat conformation. Due to such stability of the boat conformer the overall stereoselectivity of some type-II reactions may differ from the expected one.

Femtosecond Dynamics of Norrish Type-II Reactions: Nonconcerted Hydrogen-Transfer and Diradical Intermediacy

Die Norrish-Typ-II-Spaltung und die McLafferty-Umlagerung, die beide den intramolekularen Transfer eines γ-H-Atoms beinhalten, können auf der Femtosekunden-Zeitskala unterschieden werden. Bei der McLafferty-Umlagerung wird ein Keton in ionische Fragmente gespalten, während bei seiner Norrish-Typ-II-Spaltung ein Diradikal entsteht, das dann entweder cyclisiert oder in Fragmente zerfällt (siehe Schema). Für die Norrish-Typ-II-Spaltung wurde die Dauer des H-Transfers zu 70 – 90 fs bestimmt, und die Lebensdauer des untersuchten Diradikal-Intermediats beträgt 400 – 700 ps.

Femtosecond Dynamics of Norrish Type-II Reactions: Nonconcerted Hydrogen-Transfer and Diradical Intermediacy.

Norrish type-II and McLafferty rearrangements, which both involve an intramolecular transfer of a gamma H atom, can be differentiated on the femtosecond time scale. The McLafferty rearrangement results in ion fragmentation of the parent ketone, whereas the Norrish type-II reaction leads to a diradical species, which then either cyclizes or fragments (see scheme). For Norrish type-II reactions, the reaction time for the transfer of the hydrogen atom is within 70 - 90 fs, and the lifetime of the diradical intermediate is in the range of 400 - 700 ps at the total energy studied.