Transformation In Biological Systems Research Articles

Endogenous Photosensitizers in Human Skin.

Endogenous photosensitizers play a critical role in both beneficial and harmful light-induced transformations in biological systems. Understanding their mode of action is essential for advancing fields such as photomedicine, photoredox catalysis, environmental science, and the development of sun care products. This review offers a comprehensive analysis of endogenous photosensitizers in human skin, investigating the connections between their electronic excitation and the subsequent activation or damage of organic biomolecules. We gather the physicochemical and photochemical properties of key endogenous photosensitizers and examine the relationships between their chemical reactivity, location within the skin, and the primary biochemical events following solar radiation exposure, along with their influence on skin physiology and pathology. An important take-home message of this review is that photosensitization allows visible light and UV-A radiation to have large effects on skin. The analysis presented here unveils potential causes for the continuous increase in global skin cancer cases and emphasizes the limitations of current sun protection approaches.

Interaction of mercury species with proteins: towards possible mechanism of mercurial toxicology.

The nature of the binding of mercurials (organic and inorganic) and their subsequent transformations in biological systems is a matter of great debate as several different hypotheses have been proposed and none of them has been conclusively proven to explain the characteristics of Hg binding with the proteins. Thus, the chemical nature of Hg-protein binding through the possible transportation mechanism in living tissues is critically reviewed herein. Emphasis is given to the process of transportation, and binding of Hg species with selenol-containing biomolecules that are appealing for toxicological studies as well as the advancement of environmental and biological research.

Polymer Materials Synthesized through Cell-Mediated Polymerization Strategies for Regulation of Biological Functions

ConspectusAs essential components of living organisms, biomacromolecules construct cell scaffolds and regulate cell activities and biological functions through chemical transformations in biological systems. Inspired by the functional evolution in the formation of natural structures, in situ polymerization methods have been developed to create functional synthetic macromolecules inside or on the surface of living cells. Given the diversity of cell species and the complexity of biological pathways, selected strategies can be employed to control the synthesis of functional polymers that utilize the dynamic cellular microenvironment.In this Account, we summarize recent work in the field of designing cell-mediated in situ polymerization methods, with which we demonstrate their application prospects including tumor cell labeling and treatment, microbial photosynthetic efficiency regulation, and hydrogel generation. The purpose of these efforts is to design polymerization reactions in response to endogenous or exogenous stimuli and to describe the underlying response mechanisms. By reasonable design of molecular structures, in situ synthesized polymers in the cell microenvironment implement regulation of biological functions. For example, using specific redox activity combined with light irradiation, bacteria can mediate the generation of functional polymers as the encapsulating matrix or with antibacterial effects. Conjugated polymers synthesized on the microalgae surface expanded the spectral absorption and improved photosynthetic efficiency. Meanwhile, characteristics of the cellular microenvironment could initiate various polymerization reactions inside living cells, including oxidative thiol cross-linking, condensation polymerization, and free radical polymerization. These reactions can be selectively conducted with reactive species generated in tumor cells, and the resulting polymers showed prolonged retention inside cells for modulating cell behaviors. Further development of cell-mediated polymerization strategies would provide an innovative platform for research and applications of multifunctional biomaterials and engineered biohybrid systems.

Bio-inspired Water-Driven Catalytic Enantioselective Protonation.

Catalytic enantioselective protonation of a prochiral carbanion in water is a common transformation in biological systems, but has been beyond the capability of synthetic chemists since unusually rapid movement of a proton in water leads to uncontrolled racemic protonation. Herein we show a crucial role of water, which enables a highly enantioselective glyoxalase I-mimic catalytic isomerization of hemithioacetals which proceeds via enantioselective protonation of an ene-diol intermediate. The use of on-water condition turns on this otherwise extremely unreactive catalytic reaction as a result of the strengthened hydrogen bonds of water molecules near the hydrophobic reaction mixture. Furthermore, under on-water conditions, especially under biphasic microfluidic on-water conditions, access of bulk water into the enantio-determining transition state is efficiently blocked, consequently enabling the enantioselective introduction of a highly ungovernable proton to a transient enediol intermediate, which mimics the action of enzymes.

Design of tandem catalyst by co-immobilization of metal and enzyme on mesoporous foam for cascaded synthesis of (R)-phenyl ethyl acetate

Co-operative and complex catalytic transformations in biological systems comprise a set of diverse reactions in a single compartment. Herein, palladium and Cal B lipase were sequentially co-immobilized in the microenvironment of mesocellular foam to mimic biological systems and fully characterized. At optimal conditions, complete hydrogenation of acetophenone was achieved at atmospheric hydrogen pressure. The in-situ formed racemic 1-phenyl ethanol was then kinetically resolved selectively using lipase immobilized on the same support using vinyl acetate as (R)-phenylethyl acetate. For comparison, a single pot reaction was also conducted wherein supply of hydrogen was discontinued after complete conversion of acetophenone and further kinetic resolution was carried out in nitrogen atmosphere by adding vinyl acetate to system. The reaction showed complete conversion in 10h for hydrogenation step while lipase catalyzed gave 49.11% of selectivity towards R enantiomer with respect to racemic mixture with 100% enantiomeric excess (ee). The designed tandem catalyst avoids the use of multiple supports, purification of intermediate product as well as use of multiple reactors making process green and economical.

Validation of Ru(II)‐caged Abiraterone as a Chemical Tool for Controlling CYP17A1 Activity with Visible Light

Cytochromes P450 (CYP) enzymes are ubiquitous heme‐containing proteins catalyzing numerous and varied biosynthetic and detoxification transformations in biological systems. Potent and selective inhibitors have been aggressively pursued as chemical tools, drugs, and insecticides, but lack spatial and temporal control over CYP inhibition in vitro and in vivo. Metal‐caged versions of such inhibitors with photoactivated release can allow researchers to interrogate biological systems spatiotemporally. Here, a novel Ru(II)‐caged complex was designed and synthesized with the CYP17A1 inhibitor abiraterone, a prostate cancer drug. While the intact caged complex is non‐toxic and exceptionally stable in the dark, upon irradiation with low energy visible light abiraterone is rapidly released. In the dark the Ru(II) caged abiraterone does not bind to CYP17A1, but light exposure results in the released abiraterone binding to CYP17A1. This binding is observed as a type II shift consistent with the inhibitor nitrogen coordinating to the CYP17A1 heme iron with a high affinity, similar to abiraterone itself. Additionally, dark Ru(II)‐abiraterone is nontoxic to DU145 human prostate cancer cells, but light‐exposed Ru(II)‐abiraterone and abiraterone resulted in similar toxicity. Overall, this demonstrates that metal‐caged inhibitors can be designed with ideal properties as potent and selective chemical tools controlled by visible light in a biological setting.Support or Funding InformationNIH (EB 016072) and NSF (CHE1212281)

An Endoperoxide Reactivity-Based FRET Probe for Ratiometric Fluorescence Imaging of Labile Iron Pools in Living Cells.

Iron is essential for sustaining life, as its ability to cycle between multiple oxidation states is critical for catalyzing chemical transformations in biological systems. However, without proper regulation, this same redox capacity can trigger oxidative stress events that contribute to aging along with diseases ranging from cancer to cardiovascular and neurodegenerative disorders. Despite its importance, methods for monitoring biological iron bound weakly to cellular ligands−the labile iron pool−to generate a response that preserves spatial and temporal information remain limited, owing to the potent fluorescence quenching ability of iron. We report the design, synthesis, and biological evaluation of FRET Iron Probe 1 (FIP-1), a reactivity-based probe that enables ratiometric fluorescence imaging of labile iron pools in living systems. Inspired by antimalarial natural products and related therapeutics, FIP-1 links two fluorophores (fluorescein and Cy3) through an Fe(II)-cleavable endoperoxide bridge, where Fe(II)-triggered peroxide cleavage leads to a decrease in fluorescence resonance energy transfer (FRET) from the fluorescein donor to Cy3 acceptor by splitting these two dyes into separate fragments. FIP-1 responds to Fe(II) in aqueous buffer with selectivity over competing metal ions and is capable of detecting changes in labile iron pools within living cells with iron supplementation and/or depletion. Moreover, application of FIP-1 to a model of ferroptosis reveals a change in labile iron pools during this form of cell death, providing a starting point to study iron signaling in living systems.

Initiating nuclear-chemical transformations in native systems: Phenomenology

A possible mechanism of nuclear transformations in biological systems in vivo is proposed. Reasons why there is no ionizing radiation that could be detrimental to native systems during the corresponding nuclear reactions are given. It is established that the initial stage of these processes is associated with that of ATP hydrolysis, which initiates the action of the inner-shell electron of an atom participating in the reaction on its nucleus according to the mechanism of weak nuclear interaction. This results in the formation of a nucleus in a metastable state with a disturbed nucleon structure and a charge one unit lower than that of the initial nucleus. It is also assumed that the atom participating in the reaction is adsorbed near the mouth of one of the transport ATPases in the cell’s cytoplasmic membrane, and the reason for the initiating impact the electron has on the nucleus is due to the emergence of a local electric field formed during ATP hydrolysis near the ion channel of a donor–acceptor pair of charges that is opposite to the direction of the average membrane field. It is concluded that as a result of the key role of weak nuclear interaction in these processes, the energy of nuclear transformations in biological systems in vivo is released through the emission of neutrino–antineutrino pairs that are harmless to living organisms.

Building reactive copper centers in human carbonic anhydrase II

Reengineering metalloproteins to generate new biologically relevant metal centers is an effective a way to test our understanding of the structural and mechanistic features that steer chemical transformations in biological systems. Here, we report thermodynamic data characterizing the formation of two type-2 copper sites in carbonic anhydrase and experimental evidence showing one of these new, copper centers has characteristics similar to a variety of well-characterized copper centers in synthetic models and enzymatic systems. Human carbonic anhydrase II is known to bind two Cu(2+) ions; these binding events were explored using modern isothermal titration calorimetry techniques that have become a proven method to accurately measure metal-binding thermodynamic parameters. The two Cu(2+)-binding events have different affinities (K a approximately5×10(12) and 1×10(10)), and both are enthalpically driven processes. Reconstituting these Cu(2+) sites under a range of conditions has allowed us to assign the Cu(2+)-binding event to the three-histidine, native, metal-binding site. Our initial efforts to characterize these Cu(2+) sites have yielded data that show distinctive (and noncoupled) EPR signals associated with each copper-binding site and that this reconstituted enzyme can activate hydrogen peroxide to catalyze the oxidation of 2-aminophenol.

Chemical Transformations of Nanosilver in Biological Environments

The widespread use of silver nanoparticles (Ag-NPs) in consumer and medical products provides strong motivation for a careful assessment of their environmental and human health risks. Recent studies have shown that Ag-NPs released to the natural environment undergo profound chemical transformations that can affect silver bioavailability, toxicity, and risk. Less is known about Ag-NP chemical transformations in biological systems, though the medical literature clearly reports that chronic silver ingestion produces argyrial deposits consisting of silver-, sulfur-, and selenium-containing particulate phases. Here we show that Ag-NPs undergo a rich set of biochemical transformations, including accelerated oxidative dissolution in gastric acid, thiol binding and exchange, photoreduction of thiol- or protein-bound silver to secondary zerovalent Ag-NPs, and rapid reactions between silver surfaces and reduced selenium species. Selenide is also observed to rapidly exchange with sulfide in preformed Ag(2)S solid phases. The combined results allow us to propose a conceptual model for Ag-NP transformation pathways in the human body. In this model, argyrial silver deposits are not translocated engineered Ag-NPs, but rather secondary particles formed by partial dissolution in the GI tract followed by ion uptake, systemic circulation as organo-Ag complexes, and immobilization as zerovalent Ag-NPs by photoreduction in light-affected skin regions. The secondary Ag-NPs then undergo detoxifying transformations into sulfides and further into selenides or Se/S mixed phases through exchange reactions. The formation of secondary particles in biological environments implies that Ag-NPs are not only a product of industrial nanotechnology but also have long been present in the human body following exposure to more traditional chemical forms of silver.

Catalytic enantioselective syn hydration of enones in water using a DNA-based catalyst

The enantioselective addition of water to olefins in an aqueous environment is a common transformation in biological systems, but was beyond the ability of synthetic chemists. Here, we present the first examples of a non-enzymatic catalytic enantioselective hydration of enones, for which we used a catalyst that comprises a copper complex, based on an achiral ligand, non-covalently bound to (deoxy)ribonucleic acid, which is the only source of chirality present under the reaction conditions. The chiral β-hydroxy ketone product was obtained in up to 82% enantiomeric excess. Deuterium-labelling studies demonstrated that the reaction is diastereospecific, with only the syn hydration product formed. So far, this diastereospecific and enantioselective reaction had no equivalent in conventional homogeneous catalysis.

Organocatalytic Biomimetic Reduction of Conjugated Nitroalkenes

A thiourea-catalyzed biomimetic reduction of conjugated nitroalkenes has been developed. Various aromatic and aliphatic conjugated nitroalkenes can be reduced to give the respective nitroalkanes with good yields under mild conditions. This protocol is not only practical, but may also provide insight into the mechanisms of redox transformations in biological systems.

Drawing the Line: Some Observations on an Art/Science Collaboration

The authors describe their project Metamorphosis & Design, an examination of the place of design and transformation in biological systems across research areas from nanofibers to cuttlefish display. They also discuss the collaborative process between artist and scientists.

Canalization as a non-genetic source of adaptiveness during morphogenesis: experimental evidence from analysis of reproductive development in Sorghum bicolor

In Sorghum bicolor, perturbations in reproductive development observed following salt-treatment also influence progeny grown in the absence of NaCl. However, a developmental reversion of these modifications may be observed throughout two successive generations. This response, termed canalization, does not spontaneously occur following growth in the absence of NaCl, but is triggered by the level of perturbation in parental expression of reproductive characters. Moreover, canalization is not specific to the perturbed character, but it includes modifications in reproductive development as a whole. A decrease in developmental variability coincides with amplitude of the developmental reversion. This phenomenon is interpreted as an evidence for orientation of the developmental process towards the lowest free-energy state of the ‘epigenetic landscape’. Involvement of this phenomenon of canalization in developmental stability, adaptiveness, and evolution is discussed. Moreover, these results point to the need for a posteriori methods of investigations in order to analyze self-organized transformations in biological systems.

The relationship between cerium and manganese oxidation in the marine environment

The microbially mediated oxidation of Ce(II1) and Mn(I1) in surface waters of Vineyard Sound, Massachusetts, has been studied to evaluate the relationship between these two processes under different experimental conditions. These data, combined with earlier observations showing that Ce(II1) and Mn(I1) specific oxidation rates covary over a wide range of environments, suggest a close mechanistic relationship between the two processes which contributes to the marked similarities in the geochemistry of each element. Oxidation of Ce(II1) and Mn(I1) at different oxygen concentrations, pH, and concentrations of Mn(II), Ce(III), and Pr(II1) was studied with radiotracers. For both elements, oxidation was inhibited in the absence of oxygen. Ce(II1) oxidation was inhibited by Mn(I1) and vice versa, probably due to competitive inhibition within a common oxidative pathway. Pr(III), a nonredox analog of Ce(III), did not inhibit Mn(I1) oxidation nearly as effectively as Ce(II1) did, indicating that inhibition was not exclusively due to competition at a common binding site but that a redox step must also be involved. Both reactions exhibited a modest dependence on pH which was much smaller than would be expected for nonbiological oxidation. The results are consistent with a common oxidative pathway for Ce and Mn and indicate that an alternative process, nonbiological Ce oxidation on freshly formed Mn oxides, is unlikely. The results also illustrate the potential usefulness of Ce(II1) and Pr(II1) as probes of Mn uptake and redox transformations in biological systems.

Entropy and information in evolving biological systems

Integrating concepts of maintenance and of origins is essential to explaining biological diversity. The unified theory of evolution attempts to find a common theme linking production rules inherent in biological systems, explaining the origin of biological order as a manifestation of the flow of energy and the flow of information on various spatial and temporal scales, with the recognition that natural selection is an evolutionarily relevant process. Biological systems persist in space and time by transfor ming energy from one state to another in a manner that generates structures which allows the system to continue to persist. Two classes of energetic transformations allow this; heat-generating transformations, resulting in a net loss of energy from the system, and conservative transformations, changing unusable energy into states that can be stored and used subsequently. All conservative transformations in biological systems are coupled with heat-generating transformations; hence, inherent biological production, or genealogical proesses, is positively entropic. There is a self-organizing phenomenology common to genealogical phenomena, which imparts an arrow of time to biological systems. Natural selection, which by itself is time-reversible, contributes to the organization of the self-organized genealogical trajectories. The interplay of genealogical (diversity-promoting) and selective (diversity-limiting) processes produces biological order to which the primary contribution is genealogical history. Dynamic changes occuring on times scales shorter than speciation rates are microevolutionary; those occuring on time scales longer than speciation rates are macroevolutionary. Macroevolutionary processes are neither redicible to, nor autonomous from, microevolutionary processes.

ES&T Critical Reviews: Transformations of halogenated aliphatic compounds

This article summarizes and systematizes the current understanding of abiotic and biotic chemistry of halogenated aliphatic compounds. Knowledge of abiotic transformations can provide a conceptual framework for understanding biologically mediated transformations. Most abiotic transformations are slow, but they can still be significant within the time scales commonly associated with ground water movement. In contrast, biotic transformations typically proceed much faster, provided that there are sufficient substrate and nutrients and a microbial population that can mediate such transformation. Recent studies, which describe transformations of halogenated aliphatic compounds in microbial and mammalian systems, are also discussed. These studies reveal broad patterns of transformation in biological systems in general. 114 references, 8 figures, 12 tables.

Diffusion with chemical reaction in biological systems.

The interplay between diffusion and chemical transformation takes place in practically an infinite number of systems, either in nature or in the chemical industry. A variety of academic disciplines have actively studied the phenomena of diffusion with chemical reaction in order to understand the basic laws and to utilize them in predicting the behavior of systems or to design chemical processes which produce desirable species. Obviously, the study of mass transport and chemical transformation in biological systems is of great importance in the biological sciences. Likewise, the chemical reactions of molecules in industrial systems often involve significant diffusion effects and the interplay of the two effects needs to be understood to design efficient chemical systems. The laws that describe diffusion with chemical reaction are very general and apply to very disparate systems. As was pointed out by Weisz (1973) in an informative review article, discoveries made in various disciplines often were made independently of each other. The emergence of the interdisciplinary field of bioengineering has helped in bringing together knowledge developed in engineering, the pure and the biological sciences.

The chemical structure of prostaglandin X (prostacyclin)

The chemical structure of prostaglandin X, the anti-aggregatory substance derived from prostaglandin endoperoxides, is 9-deoxy-6, 9α-epoxy-Δ 5-PGF 1α. The stable compound formed when prostaglandin X undergoes a chemical transformation in biological systems is 6-keto-PGF 1α. Prostaglandin X is stabilized in aqueous preparations by raising the pH to 8.5 or higher. The trivial name prostacyclin is proposed for 9-deoxy-6, 9α-epoxy-Δ 5-PGF 1α.

Energy Metabolism Energy Transformation in Biological Systems: In Tribute to Fritz Lipmann on His 75th Birthday American Elsevier

Energy Metabolism Energy Transformation in Biological Systems: In Tribute to Fritz Lipmann on His 75th Birthday American Elsevier