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Possible Mechanisms of Fullerene C60 Antioxidant Action

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Novel mechanism of antioxidant activity of buckminsterfullerene C60 based on protons absorbing and mild uncoupling of mitochondrial respiration and phosphorylation was postulated. In the present study we confirm this hypothesis using computer modeling based on Density Functional Theory. Fullerene's geroprotective activity is sufficiently higher than those of the most powerful reactive oxygen species scavengers. We propose here that C60 has an ability to acquire positive charge by absorbing inside several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and phosphorylation. This, in turn, leads to the decrease in ROS production.
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Volume , Article ID , pages.//
Research Article
Possible Mechanisms of Fullerene C60 Antioxidant Action
V. A. Chistyakov,1Yu. O. Smirnova,2,3 E. V. Prazdnova,1and A. V. Soldatov2
1Research Institute of Biology, Southern Federal University, Rostov-on-Don 344090, Russia
2Research Center for Nanoscale Structure of Matter, Southern Federal University, Rostov-on-Don 344090, Russia
3Department of Physics, Purdue University, West Lafayette, IN 47907, USA
Correspondence should be addressed to Yu. O. Smirnova;
Received  June ; Revised  August ; Accepted  September 
Academic Editor: Claiton Leonetti Lencina
Copyright ©  V. A. Chistyakov et al. is is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
Novel mechanism of antioxidant activity of buckminsterfullerene C60 based on protons absorbing and mild uncoupling of
mitochondrial respiration and phosphorylation was postulated. In the present study we conrm this hypothesis using computer
modeling based on Density Functional eory. Fullerenes geroprotective activity is suciently higher than those of the most
powerful reactive oxygen species scavengers. We propose here that C60 has an ability to acquire positive charge by absorbing inside
several protons and this complex could penetrate into mitochondria. Such a process allows for mild uncoupling of respiration and
phosphorylation. is, in turn, leads to the decrease in ROS production.
1. Introduction
Reactive oxygen species (ROS) are able to cause oxidative
damage to DNA, lipids, and proteins and are known to
be the key regulators of cellular signaling. In spite of the
criticismfromanumberofresearchers[] free-radical theory
occupies a pivotal position in modern biological concepts
of aging []. e ability to retard senescence is typical for
many antioxidants []. Well-known ability of fresh vegeta-
bles, fruits, red wines, and spices to stimulate longevity is
largely determined by the existence of compounds such as
deprotonated xanthones [], carotenoids [], anthocyanins
and pyranoanthocyanins [], and avonoids and terpenoids
[]. ese compounds exhibit a broad spectrum of oxyradical
quenching activity based on reactions of single electron
transfer, hydrogen atom transfer, sequential electron proton
transfer, proton coupled electron transfer, radical adduct
formation, and iron chelation [,].
IntherecentstudyBaatietal.[] showed that the oral
administration of the fullerene C60 suspension in olive oil
retards senescence of rats. Herewith, median and maximum
life span increase approximately twice. Moreover, it was
shown that rats treated with fullerene C60 demonstrated high
resistance to carbon tetrachloride. Toxicity of this substance
is mediated by ROS generation []. According to this fact and
results of biochemical tests fullerene C60 was proposed to be
of high antioxidant activity in vivo. Due to the free-radical
theory of aging, highly active antioxidant activity can be the
basis for unique antiaging (geroprotective) properties.
Fullerene C60 isknowntobeabletoinactivatehydroxyl
radicals by attaching to double bonds []. However, this
mechanism cannot explain sucient (near two times) incre-
ase in lifespan of rats. Such kind of antioxidative activity is
also attributed to natural phenolic antioxidants that do not
possess high senescence retarding activity []. We propose
that there is an additional mechanism involved in fullerene
anti-aging activity. Respiratory chain located in the inner
mitochondrial membrane is the main source of superoxide
anion radicals, which lead to a cascade of other toxic ROS.
In this connection mitochondrial-targeted antioxidants like
lipophilic cations (Skulachev ions) with antioxidant load
[] are the most eective antiaging agents (geroprotectors)
among synthetic compounds.
Accumulation of Skulachev ions in the mitochondria is
based on the transmembrane potential dierence generated
of inner membrane of mitochondria has positive charge and
the inner side has negative charge. So, lipophilic cations are
concentrating in mitochondria via electric eld forces [].
BioMed Research International
(a) (b)
F : e results of DFT geometry optimization for one (a) and six (b) protons and fullerene. Initially protons were placed outside the
fullerene and then the conguration that has the minimum value of total energy was found as a result of DFT geometry optimization. As a
result, all protons appeared to be inside the fullerene. For the simulation, GGA-BLYP exchange-correlation potential was used. Carbon atoms
are shown in grey and protons are shown in black.
e lipophilic properties of fullerene C60 are well known [].
In addition, Wong-Ekkabut et al. showed using molecular
dynamics simulations []thatC
60 fullerene is capable of
penetrating into membrane and accumulates in the middle
of lipid bilayer. However, the simulation does not consider
the possible presence of fullerene and/or membrane charge.
We suppose that fullerene is capable of absorbing protons and
obtaining positive charge, which allows it to be delivered into
the mitochondria. us, superoxide anion-radical generation
is decreased by mild uncoupling of respiration and phos-
phorylation []. In the present study we perform theoretical
analysis of the fullerene C60 ability to acquire positive charge
and to absorb protons to prove that the proposed mechanism
indeed may take place.
2. Methods
All the computer simulations were performed within the
framework of Density Functional eory (DFT) for solving
odinger equation [], which has been used for the
investigation of antioxidants previously []. In the present
work, DFT implemented in ADF  code was used [].
Initially from one up to seven protons were placed outside the
fullerene and then the most probable atomic conguration
was found by minimizing the total energy of the system
during the process of geometry optimization, that is, nding
a stable conguration of the system that corresponds to
the minimum of total energy. For the exchange-correlation
part of molecule potential General Gradient Approximation
(GGA) was used in both GGA-BLYP [] and GGA-BLYP-
D [,] forms, but all nal results were obtained using
GGA-BLYP potential. Basis sets are DZ (double-𝜁)withinthe
calculations including water molecules around C60 and TZP
(triple-𝜁) within the calculations without taking into account
the water molecules around “C60 plus-protons” system.
3. Results
At rst step an interaction between single proton and
fullerene was simulated. e proton was placed outside the
C60 above one of the pentagons at the distance about  ˚
from the pentagon plane. As a result, the proton transfers
fullerene at a distance about . ˚
A from the nearest carbon
atom (Figure (a)). Next, more protons were added to this
system; some of them were initially placed above pentagons,
but most were placed above hexagons. e rst two protons
were placed at maximum possible distance from each other.
All others were equally distributed around the fullerene. In all
cases protons were “absorbed” by the fullerene, and it was so
until the seventh proton was added to the system—it repulsed
from the fullerene. So, the maximum amount of protons
inside the fullerene consists of six protons (Figure (b)).
It is crucial to know the distribution of charge over C60 for
each conguration of protons. Figure  shows the distribu-
tion for two, four, and six protons inside the fullerene. It can
be seen that when there are two protons inside the surface of
are added the fullerene surface obtains positive charge.
Table  provides information about binding energies and
VDD charges [] for each proton added to the system. Both
charges on protons and relatively big C-H distances allow us
to suppose that protons interact with fullerene according to
donor-acceptor mechanism and do not form strong chemical
It is important to know whether the presence of other
molecules near fullerene will impact the ability of protons
to penetrate into fullerene or not. For this purpose we
performed a simulation involving water molecules which are
in the presence of both protons and water hydronium ions
will appear, water molecules can be chosen. An exchange
of protons between hydronium ions takes place in such
environment, so for some small period of time protons are
e simulation was carried out for a fullerene with single
proton placed above a pentagon and  water molecules
randomly distributed around the fullerene. It was shown
that solvent molecules do not inuence the capability of a
fullerene to absorb the proton.
BioMed Research International
MDC-d charge
F : e distribution of charge for two, four, and six protons inside the fullerene. e charge of fullerene with two protons inside is
about zero (red color) while fullerenes that have four or six protons inside obtain positive charge (green and blue color). Protons lose their
positive charge starting from positive charge (blue color) to almost zero (orange color).
T : Binding energies and VDD charges for dierent amounts
of protons added to fullerene.
Number of
Binding energy
values, eV
e Voronoi Deformation
Density (VDD)
 . .
 .
 .
 .
4. Discussion
60 accumulating in
mitochondria provides high radical scavenging activity in
this subcellular compartment, called by Skulachev the “dirt-
iest place in the cell” []. Another eective antioxidant
mechanism is based on mild uncoupling of respiration and
phosphorylation. Respiratory chain obtains electrons from
electron reduction of oxygen. But the transfer of one or two
electrons could produce the radicals that are dangerous to
cells (such as superoxide or peroxide anions).
e specic feature attributable to the generation of
ROS by mitochondria is related to the fact that the higher
is the membrane potential (the larger is the dierence in
the concentration of protons inside and outside the mito-
chondria), the higher is the level of the superoxide anion
production. As it was shown [], there is steep depen-
dence of mitochondrial superoxide-anion-radical generation
on transmembrane potential (Δ𝜓). Even a small (–%)
decline of Δ𝜓 resulted in tenfold lowering of ROS production
erefore, the so-called mild uncouplers of oxidative
phosphorylation are the substances which can move some
of the protons inside the mitochondria and can possess
an excellent oxygen-protective eect, although they are not
antioxidants in terms of chemistry [].
DFT simulations allowed us to propose the following
mechanism. C60 fullerene molecules enter the space between
inner and outer membranes of mitochondria, where the
excess of protons has been formed by diusion. In this com-
partment fullerenes are loaded with protons and acquire
positive charge distributed over their surface. Such “charge-
loaded” particles can be transferred through the inner mem-
brane of the mitochondria due to the potential dierence
generated by the inner membrane, using electrochemical
mechanism described in detail by Skulachev et al. [,]. In
this case the transmembrane potential is reduced, which in
turn signicantly reduces the intensity of superoxide anion-
radical production.
5. Conclusion
e proposed ability of C60 fullerenes to acquire positive
charge allows ascribing them to the mitochondrial-targeted
compounds. e key role of mitochondria in the cellular
regulation makes such “charge-loaded” fullerenes be of great
interest along the route for novel classes of drugs develop-
Authors’ Contribution
V. A. Chistyakov and Yu. O. Smirnova contributed equally to
this work.
e authors are grateful to Dr. V. S. Lysenko and Dr. Igor
Alperovich for valuable comments that improved the paper.
BioMed Research International
e support by Southern Federal University of Russia grants
is acknowledged.
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... Fullerenes and their derivatives are called "free radical sponges" due to their highly electron-deficient structure and accessibility to radicals [17][18][19]. In addition, the antioxidant activity [20], antibacterial activity [21], antiviral activity [22], carrier drug [23] and tumor therapy [24] activity of the fullerenes have been widely accepted in the fields of biology and medicine [25][26][27]. However, the spherical and hydrophobic surface of fullerenes often results in limited solubility in water. ...
... Given the important role that antioxidants play in cardiovascular disease, new powerful antioxidants have been the focus of attention. Previous studies have shown that C 60 not only shows great advantages in anti-oxidation but also plays a positive role in anti-apoptosis and anti-inflammatory [20,62,63]. Mei Ding et al. [64] found that fullerenol can improve cardiac function, reduce the inflammatory reaction, increase antioxidant function, and enhance the activity of Nrf2/HO-1 signaling pathway in myocardial cells. ...
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A water-soluble cube-like supramolecular cage was constructed by an engagement of six molecules through a hydrophobic effect in the water. The obtained cage could perfectly encapsulate one fullerene C60 molecule inside of the cavity and significantly improve the water-solubility of the C60 without changing the original structure. The water-soluble complex was further applied to reduce the reactive oxygen species (R.O.S.) in cardiomyocytes (FMC84) through Akt/Nrf2/HO-1 pathway. Furthermore, in the mouse model of myocardial ischemia-reperfusion injury, the application of C60 was found to be effective in reducing myocardial injury and improving cardiac function. It also reduced the levels of R.O.S. in myocardial tissue, inhibited myocardial apoptosis, and mitigated myocardial inflammatory responses. The present study provides a new guideline for constructing water-soluble C60 and verifies the important role of C60 in preventing oxidative stress-related cardiovascular disease injury.
... Hurmach et al. confirmed through two studies (2021a and 2021b) that C60 fullerene, a compound used as an antioxidant [40,41], can inhibit SARS-CoV-2 in silico and in vitro by blocking cell entry and disrupting the formation of the RdRp-nsp8 complex through stacking and steric interactions [42,43] Two studies explored the potential of quercetin, a plant flavonol with anti-inflammatory properties [44], as an agent against SARS-CoV-2. Both in vitro experiments suggested that viral replication may be reduced in a dose-dependent manner. ...
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Background: As long as COVID-19 endures, viral surface proteins will keep changing and new viral strains will emerge, rendering prior vaccines and treatments decreasingly effective. To provide durable targets for preventive and therapeutic agents, there is increasing interest in slowly mutating viral proteins, including non-surface proteins like RdRp. Methods: A scoping review of studies was conducted describing RdRp in the context of COVID-19 through MEDLINE/PubMed and EMBASE. An iterative approach was used with input from content experts and three independent reviewers, focused on studies related to either RdRp activity inhibition or RdRp mechanisms against SARS-CoV-2. Results: Of the 205 records screened, 43 studies were included in the review. Twenty five evaluated RdRp activity inhibition, and eighteen described RdRp mechanisms of existing drugs or compounds against SARS-CoV-2. In silico experiments suggested that RdRp inhibitors developed for other RNA viruses may be effective in disrupting SARS-CoV-2 replication, indicating a possible reduction of disease progression from current and future variants. In vitro, in vivo, and human clinical trial studies were largely consistent with these findings. Conclusions: Future risk mitigation and treatment strategies against forthcoming SARS-CoV-2 variants should consider targeting RdRp proteins instead of surface proteins.
... Fullerene C60 quenches ROS by accepting unpaired electrons, being able to accept six electrons simultaneously and adding up to 34 methyl radicals to the C60 sphere, hence the name 'radical sponge' [161][162][163] . In a mechanistic study, Chistyakov et al. suggested that fullerene C60 might reduce the production of superoxide anion radicals by altering the electrical potential difference in the mitochondrial membrane [164] . This is due to the special chemical structure of fullerene C60, which can absorb protons and thus acquire a positive surface charge. ...
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Reactive oxygen species (ROS) play distinct but important roles in physiological and pathophysiological processes. Recent studies on osteoarthritis (OA) have suggested that ROS plays a crucial role in its development and progression, serving as key mediators in the degradation of the extracellular matrix, mitochondrial dysfunction, chondrocyte apoptosis, and OA progression. With the continuous development of nanomaterial technology, the ROS-scavenging ability and antioxidant effects of nanomaterials are being explored, with promising results already achieved in OA treatment. However, current research on nanomaterials as ROS scavengers for OA is relatively non-uniform and includes both inorganic and functionalized organic nanomaterials. Although the therapeutic efficacy of nanomaterials has been reported to be conclusive, there is still no uniformity in the timing and potential of their use in clinical practice. This paper reviews the nanomaterials currently used as ROS scavengers for OA treatment, along with their mechanisms of action, with the aim of providing a reference and direction for similar studies, and ultimately promoting the early clinical use of nanomaterials for OA treatment. STATEMENT OF SIGNIFICANCE: Reactive oxygen species (ROS) play an important role in the pathogenesis of osteoarthritis (OA). Nanomaterials serving as promising ROS scavengers have gained increasing attention in recent years. This review provides a comprehensive overview of ROS production and regulation, as well as their role in OA pathogenesis. Furthermore, this review highlights the applications of various types of nanomaterials as ROS scavengers in OA treatment and their mechanisms of action. Finally, the challenges and future prospects of nanomaterial-based ROS scavengers in OA therapy are discussed.
... Fullerene C60 quenches ROS by accepting unpaired electrons, being able to accept six electrons simultaneously and adding up to 34 methyl radicals to the C60 sphere, hence the name 'radical sponge' [161][162][163] . In a mechanistic study, Chistyakov et al. suggested that fullerene C60 might reduce the production of superoxide anion radicals by altering the electrical potential difference in the mitochondrial membrane [164] . This is due to the special chemical structure of fullerene C60, which can absorb protons and thus acquire a positive surface charge. ...
... Among the most promising compounds considered as perspective nanodrugs are fullerenes and their derivatives [1]. Due to electronic structures and unique physical and chemical properties, fullerenes act both as pro-oxidants and as antioxidants [2,3]. This ability to either suppress or generate cytotoxic free radicals, together with a small size and a large surface area, leads to various applications in medicine [4,5]. ...
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The development of novel biologically active nanopharmaceuticals is a topical problem of medicine. Water-soluble fullerene derivatives are of particular interest due to their ability to regulate intracellular metabolism of reactive oxygen species (ROS) by direct oxidation or effects on oxidative and signaling enzymes. Here, we studied the effect of a water-soluble chlorine-containing derivative of C60 fullerene on human embryonic lung fibroblasts. MTT tests, intracellular ROS visualization, detection of the ROS-associated gene and protein expression, repair, cell proliferation and cell cycle regulation, and quantitation of oxidative DNA damage were used. Within the first three hours after exposure, antioxidant effects were revealed. Later, oxidative damage appeared. Thus, the studied compound had an ambiguous effect on ROS metabolism associated with a switch in the regulatory effect, which must be taken into account when assessing its biological activity and toxicity.
Introduction: Cyclooxygenase (COX), in literature, known as prostaglandin-endoperoxide synthase (PTGS), is an enzyme that is responsible for the formation of prostanoids, including thromboxane and prostaglandins from arachidonic acid. COX-1 does housekeeping activity, whereas COX-2 induces inflammation. Continuous rise in COX-2 gives birth to chronic pain-associated disorders, i.e., arthritis, cardiovascular complications, macular degeneration, cancer, and neurodegenerative disorders. Despite their potent anti-inflammatory effects, the detrimental effects of COX-2 inhibitors coexist in healthy tissues. Non-preferential NSAIDs cause gastrointestinal discomfort, whereas selective COX-2 inhibitors exert higher cardiovascular risk and renal impairment on chronic use. Area covered: This review paper covers key patents published between 2012-2022 on NSAIDs and coxibs, highlighting their importance, mechanism of action, and patents related to formulation and drug combination. So far, several drug combinations with NSAIDS have been used in clinical trials to treat chronic pain besides combating the side effects. Conclusion: Emphasis has been given on the formulation, drug combination, administration routes-modification, and alternative routes, i.e., parenteral, topical, and ocular DEPOT, improving its risk-benefit ratio of NSAIDs to improvise their therapeutic availability and minimize the adverse effects. Considering the wide area of research on COX-2 and ongoing studies, and future scope of view for the better use of the NSAIDs in treating debilitating disease-associated algesia.
This review aims to systematize data on the construction and applications of bacterial lux-biosensors in various fields ranging from investigation of gene regulation and regulatory networks to the new probiotics' search and ecotoxicological research. The typical technical solutions and devices required for diverse tasks applying lux-biosensors are reviewed. Aspects of the application of lux-biosensors in fundamental researches, such as the study of oxidative stress, heat shock, DNA-damaging, pro- and antioxidant activities, are also considered. This technology allows rapid screening of the biological activities of newly synthesized compounds, which could be applied as components for fuels, household chemicals, and drugs. Works related to the ecological state assessment on water resources are also described. The use of lux-biosensor complexes based on different organisms, including both gram-positive and gram-negative bacteria, makes toxicological investigations more comprehensive. Bacterial lux-biosensors based on Escherichia coli can be used as a model for evaluation of the effect of certain substances on the transmembrane potential in mitochondria, albeit with extrapolation to a certain extent. Another aspect that draws our interest is that biosensors are able to help predict some systemic properties of probiotics. In the future, it's quite promising to see more applications of lux-biosensors for environmental control, microbial-microbial interaction assessment, antioxidant action mechanism studies and toxicological studies in the development of new drugs.
Multi-walled carbon nanotubes (MWCNTs) are tubular-shaped carbon allotropes, composed of multiple concentric graphene cylinders. The extended systems of conjugated double bonds, that MWCNTs are constituted by, provide them with high electron affinities, enabling them to act as electron donors or acceptors. Consequently, their potential biomedical applications, as synthetic antioxidant agents, are of particular interest. Based on the above, the purpose of the present study was to evaluate the intrinsic antioxidant properties of pristine and carboxylated MWCNTs, as well as of novel hybrid nanocomposites of MWCNTs and inorganic nanoparticles. To this end, after the synthesis and characterization of MWCNTs, their antiradical, reducing, and antigenotoxic properties were assessed in cell-free assays, using a methodological approach that has been recently proposed by our research group. According to our results, most of the tested MWCNTs exhibited strong antioxidant activities. More elaborately, the hybrid material of MWCNTs and ferrous oxide nanoparticles, i.e., CNTs@Fe3O4, showed robust scavenging capacities in all free-radical scavenging assays examined. As regards reducing properties, the pristine MWCNTs, i.e., CNTs-Ref, exhibited the greater electron donating capacity. Finally, in terms of antigenotoxic properties, the hybrid material of MWCNTs and silicon carbide nanoparticles, i.e., CNTs@SiC, exhibited potent ability to inhibit the formation of peroxyl radicals, thus preventing from the oxidative DNA damage. Conclusively, our findings suggest that the MWCNTs of the study could be considered as promising broad-spectrum antioxidants, however, further investigations are required to evaluate their toxicological profile in cell-based and in vivo systems.
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Plastoquinone, a very effective electron carrier and antioxidant of chloroplasts, was conjugated with decyltriphenylphosphonium to obtain a cation easily penetrating through membranes. This cation, called SkQ1, is specifically targeted to mitochondria by electrophoresis in the electric field formed by the mitochondrial respiratory chain. The respiratory chain also regenerates reduced SkQ1H2 from its oxidized form that appears as a result of the antioxidant activity of SkQ1H2. SkQ1H2 prevents oxidation of cardiolipin, a mitochondrial phospholipid that is especially sensitive to attack by reactive oxygen species (ROS). In cell cultures, SkQ1 and its analog plastoquinonyl decylrhodamine 19 (SkQR1) arrest H2O2-induced apoptosis. When tested in vivo, SkQs (i) prolong the lifespan of fungi, crustaceans, insects, fish, and mice, (ii) suppress appearance of a large number of traits typical for age-related senescence (cataract, retinopathies, achromotrichia, osteoporosis, lordokyphosis, decline of the immune system, myeloid shift of blood cells, activation of apoptosis, induction of β-galactosidase, phosphorylation of H2AX histones, etc.) and (iii) lower tissue damage and save the lives of young animals after treatments resulting in kidney ischemia, rhabdomyolysis, heart attack, arrhythmia, and stroke. We suggest that the SkQs reduce mitochondrial ROS and, as a consequence, inhibit mitochondriamediated apoptosis, an obligatory step of execution of programs responsible for both senescence and fast “biochemical suicide” of an organism after a severe metabolic crisis.
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Many insights into the mechanisms and signaling pathways underlying aging have resulted from research on the nematode Caenorhabditis elegans. In this paper, we discuss the recent findings that emerged using this model organism concerning the role of reactive oxygen species (ROS) in the aging process. The accrual of oxidative stress and damage has been the predominant mechanistic explanation for the process of aging for many years, but reviewing the recent studies in C. elegans calls this theory into question. Thus, it becomes more and more evident that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it seems more likely that tightly controlled concentrations of ROS and fluctuations in redox potential are important mediators of signaling processes. We therefore discuss some theories that explain how redox signaling may be involved in aging and provide some examples of ROS functions and signaling in C. elegans metabolism. To understand the role of ROS and the redox status in physiology, stress response, development, and aging, there is a rising need for accurate and reversible in vivo detection. Therefore, we comment on some methods of ROS and redox detection with emphasis on the implementation of genetically encoded biosensors in C. elegans.
We present a density functional theory (DFT) and time-dependent density functional theory (TD-DFT) study on the stability, antioxidant properties with respect to the single electron transfer mechanism, and electronic absorption spectra of some isomers (9-cis, 13-cis, and 15-cis) of carotenoids such as astaxanthin, lycopene, and those present in virgin olive oil (lutein, β-carotene, neoxanthin, antheraxanthin, violaxanthin, neochrome, luteoxanthin, mutatoxanthin, and violaxanthin). In general, the calculated relative stability of the cis isomers appears to be in line with experimental observations. It is predicted that the above-mentioned carotenoids (cis and trans isomers) will transfer one electron to the (•)OH radical. However, this transference is not plausible with radicals such as (•)OOH, (•)OC2H5, (•)OOC2H5, (•)NO2, and (•)OOCH2CH═CH2. On the other hand, some carotenoids (β-carotene, lycopene, lutein, astaxanthin, violaxanthin, and antheraxanthin) will likely accept, in a medium of low polarity, one electron from the radical (•)O2(-). However, neoxanthin, auroxanthin, mutatoxanthin, luteoxanthin, and neochrome would not participate in such an electronic transfer mechanism. The TD-DFT studies show that neutral species of the cis and trans isomers maintain the same color. On the contrary, the ionic species undergo a "bleaching" process where the absorption wavelengths shift to longer values (>700 nm). Additionally, the formation of a complex between astaxanthin and Cu(2+) is explored as well as the effect that the metal atom will have in the UV-vis spectrum.
Over the last decade, accumulating evidence has suggested a causative link between mitochondrial dysfunction and major phenotypes associated with aging. Somatic mitochondrial DNA (mtDNA) mutations and respiratory chain dysfunction accompany normal aging, but the first direct experimental evidence that increased mtDNA mutation levels contribute to progeroid phenotypes came from the mtDNA mutator mouse. Recent evidence suggests that increases in aging-associated mtDNA mutations are not caused by damage accumulation, but rather are due to clonal expansion of mtDNA replication errors that occur during development. Here we discuss the caveats of the traditional mitochondrial free radical theory of aging and highlight other possible mechanisms, including insulin/IGF-1 signaling (IIS) and the target of rapamycin pathways, that underlie the central role of mitochondria in the aging process.
Oxovitisin is a natural antioxidant present in aged wine and comes from the chemical transformation undergone by anthocyanins and pyranoanthocyanins. Its antioxidant radical scavenging capacity was theoretically explored by density functional theory (DFT)/B3LYP methods. The O–H bond dissociation energy (BDE), the ionization potential (IP), the proton affinity (PA), and the metal–oxovitisin binding energy (BE) parameters were computed in the gas-phase and in water and benzene solutions. Results provided molecular insight into factors that influence radical scavenging potential of this new class of anthocyanins.
Most dermatologists agree that antioxidants help fight free radical damage and can help maintain healthy skin. They do so by affecting intracellular signaling pathways involved in skin damage and protecting against photodamage, as well as preventing wrinkles and inflammation. In today's modern world of the rising nutraceutical industry, many people, in addition to applying topical skin care products, turn to supplementation of the nutrients missing in their diets by taking multivitamins or isolated, man-made nutraceuticals, in what is known as the Inside-Out approach to skin care. However, ingestion of large quantities of isolated, fragmented nutrients can be harmful and is a poor representation of the kind of nutrition that can be obtained from whole food sources. In this comprehensive review, it was found that few studies on oral antioxidants benefiting the skin have been done using whole foods, and that the vast majority of current research is focused on the study of compounds in isolation. However, the public stands to benefit greatly if more research were to be devoted toward the impact that physiologic doses of antioxidants (obtained from fruits, vegetables, and whole grains) can have on skin health, and on health in general.
We present the theoretical and technical foundations of the Amsterdam Density Functional (ADF) program with a survey of the characteristics of the code (numerical integration, density fitting for the Coulomb potential, and STO basis functions). Recent developments enhance the efficiency of ADF (e.g., parallelization, near order-N scaling, QM/MM) and its functionality (e.g., NMR chemical shifts, COSMO solvent effects, ZORA relativistic method, excitation energies, frequency-dependent (hyper)polarizabilities, atomic VDD charges). In the Applications section we discuss the physical model of the electronic structure and the chemical bond, i.e., the Kohn–Sham molecular orbital (MO) theory, and illustrate the power of the Kohn–Sham MO model in conjunction with the ADF-typical fragment approach to quantitatively understand and predict chemical phenomena. We review the “Activation-strain TS interaction” (ATS) model of chemical reactivity as a conceptual framework for understanding how activation barriers of various types of (competing) reaction mechanisms arise and how they may be controlled, for example, in organic chemistry or homogeneous catalysis. Finally, we include a brief discussion of exemplary applications in the field of biochemistry (structure and bonding of DNA) and of time-dependent density functional theory (TDDFT) to indicate how this development further reinforces the ADF tools for the analysis of chemical phenomena. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 931–967, 2001