The chemistry of boron and its speciation in plants

The chemistry and usage of B, as well as its speciation in plants, are reviewed. In the context of biology, the chemistry of the surprisingly rare element B is dominated by B-oxygen compounds. The occurrence, distribution and chemistry of these compounds are briefly described. In addition, the chemistry involved in the interaction of B–O compounds with naturally occurring molecules, particularly polyhydroxy compounds, is summarised. The essentiality of B in plants has been known for 75 years, but the biomolecule(s) with which it interacts to cause its essential function(s) remain largely unknown, although many have been suggested. Recent research on the complexation, isolation and partial characterisation of B complexes of polysaccharides, diols, and hydroxyacids is outlined. The particular importance of B interactions with cell wall components, membranes, enzymes, sugars, and polyols is discussed.     

Exploring biologically relevant chemical space with metal complexes

Altering biological processes with small synthetic molecules is a general approach for the design of drugs and molecular probes. Medicinal chemistry and chemical biology are focused predominately on the design of organic molecules, whereas inorganic compounds find applications mainly for their reactivity (e.g. cisplatin as a DNA-reactive therapeutic) or imaging properties (e.g. gadolinium complexes as MRI diagnostics). In such inorganic pharmaceuticals or probes, coordination chemistry in the biological environment or at the target site lies at the heart of their modes of action. However, past and very recent results suggest that it is also worth exploring a different aspect of metal complexes: their ability to form structures with unique and defined shapes for the design of 'organic-like' small-molecule probes and drugs. In such metal-organic compounds, the metal has the main purpose to organize the organic ligands in three-dimensional space. It is likely that such an approach will complement the molecular diversity of organic chemistry in the quest for the discovery of compounds with superior biological activities.     

Antioxidant drug mechanisms: transition metal-binding and vasodilation

In our work evaluating the antioxidant properties of a number of cardiovascular drugs, we have emphasized the importance of lipophilicity as a property contributing to antioxidant potency. Thus, the dihydropyridine calcium channel blockers and propranolol, one of the most lipophilic beta-blockers, were found to exhibit the greatest potency in membrane and cellular models. Both beta-blockers and calcium channel blockers are classified as antihypertensive agents. We found that the specific chemical moieties of various drugs may participate in the antioxidant mechanism of action. While reviewing relevant work from the past literature, it became apparent that some of the chemical moieties of antihypertensive and vasodilator drugs may bind transition metals. Thus, this present review focuses on common properties of transition metal-interaction that are shared, to a greater or lesser degree, by a number of vasoactive drugs and chemical agents. Although this observation has been pursued by other investigators in the past, we submit that the potential relevance to the newer pharmacological agents needs to be explored further. In addition, new information regarding the role of transition metals and free radicals involving vascular cells focuses greater importance on transition metal-interaction as a potential mechanism in vasodilation. This review does not intend to be inclusive of all chemical structures capable of binding transition metals; only those that are clinically relevant will be considered in some detail. Potential mechanisms of metal-chelating actions leading to vasodilation are also discussed.     

Comparison of divalent transition metal ion paraCEST MRI contrast agents

Transition-metal-ion-based paramagnetic chemical exchange saturation transfer (paraCEST) agents are a promising new class of compounds for magnetic resonance imaging (MRI) contrast. Members in this class of compounds include paramagnetic complexes of Fe^II, Co^II, and Ni^II. The development of the coordination chemistry for these paraCEST agents is presented with an emphasis on the choice of the azamacrocycle backbone and pendent groups with the goals of controlling the oxidation state, spin state, and stability of the complexes. Chemical exchange saturation transfer spectra and images are compared for different macrocyclic complexes containing amide or heterocyclic pendent groups. The potential of paraCEST agents that function as pH- and redox-activated MRI probes is discussed.     

Applications of spectral hole burning spectroscopies to antenna and reaction center complexes

The underlying principles of spectral hole burning spectroscopies and the theory for hole profiles are reviewed and illustrated with calculated spectra. The methodology by which the dependence of the overall hole profile on burn wavelength can be used to reveal the contributions from site inhomogeneous broadening and various homogeneous broadening contributions to the broad Q_y-absorption bands of cofactors is emphasized. Applications to the primary electron donor states of the reaction centers of purple bacteria and Photosystems I and II of green plants are discussed. The antenna (light harvesting) complexes considered include B800–B850 and B875 of Rhodobacter sphaeroides and the base-plate complex of Prosthecochloris aestuarii with particular attention being given to excitonic interactions and level structure. The data presented show that spectral hole burning is a generally applicable low temperature approach for the study of excited state electronic and vibrational (intramolecular, phonon) structures, structural heterogeneity and excited state lifetimes.William E. Catron Fellow.     

Human hemoglobin: polymorphism, neutrality of variants, evolutionary aspect

Integrated analysis of the polymorphism of human hemoglobin has been made using populational genetics, hematological, physiological, protein chemistry and molecular biology data. The known variants of human hemoglobin are conventionally classified as "widely common", "less common" and "rare", depending on their contribution to polymorphism. The importance of homeostasis and compensatory reactions for maintaining the resistance of the human body against mutant hemoglobins is emphasized. Hb D Punjab and Hb O Arab being relatively neutral, the genetic structure of populations may restrict their distribution. A hypothesis is put forward concerning the possible role of an increased local conformational mobility of protein in creating neutral protein variants. It is proposed to discriminate between truly neutral and pseudoneutral protein variants. In case of possible changes in the genetic and environmental factors, the former are not subject to selection, while the latter may be. Contribution to neutral evolution can be made only by truly neutral variants. In a compensated heterozygotic state the truly neutral and pseudoneutral variants may give rise to new functions and adaptively valuable properties in protein. The evolution of proteins is believed to proceed from a stage which is consistent with M. Kimura's concept of neutrality of protein polymorphism toward a stage which is consistent with the concept of selectionism. It is concluded, that the currently observed degree of polymorphism of human hemoglobin corresponds to the present stage of molecular evolution of the protein.     

Relationships between nitric oxide, nitroxyl ion, nitrosonium cation and peroxynitrite.

This review is concerned mainly with the three redox-related, but chemically distinct, species NO-, NO. and NO+, with greatest emphasis being placed on the chemistry and biology of the nitroxyl ion. Biochemical routes for the formation of nitroxyl ion and methods for showing the intermediacy of this species are discussed, together with chemical methods for generating nitroxyl ion in solution. Reactions of nitroxyl ion with NO., thiols, iron centres in haem and with dioxygen are reviewed The significance of the reaction between NO- and dioxygen as a source of peroxynitrite is assessed, and attention drawn to the possible significance of the spin state of the nitroxyl ion in this context. The biological significance of nitrosation and the importance of S-nitrosothiols and certain metal nitrosyl complexes as carriers of NO+ at physiological pH is stressed. Some features in the chemistry of peroxynitrite are noted.     

Magnetic Circular Dichroism of Porphyrin Lanthanide M3+ Complexes

Lanthanide complexes exhibit interesting spectroscopic properties yielding many applications as imaging probes, natural chirality amplifiers, and therapeutic agents. However, many properties are not fully understood yet. Therefore, we applied magnetic circular dichroism (MCD) spectroscopy, which provides enhanced information about the underlying electronic structure to a series of lanthanide compounds. The metals in the M³⁺ state included Y, La, Eu, Tb, Dy, Ho, Er, Tm, Yb, and Lu; the spectra were collected for selected tetraphenylporphin (TPP) and octaethylporphin (OEP) complexes in chloroform. While the MCD and UV‐VIS absorption spectra were dominated by the porphyrin signal, metal binding significantly modulated them. MCD spectroscopy was found to be better suited to discriminate between various species than absorption spectroscopy alone. The main features and trends in the lanthanide series observed in MCD and absorption spectra of the complexes could be interpreted at the Density Functional Theory (DFT) level, with effective core potentials on metal nuclei. The sum over state (SOS) method was used for simulation of the MCD intensities. The combination of the spectroscopy and quantum‐chemical computations is important for understanding the interactions of the metals with the organic compounds. Chirality 26:655–662, 2014. © 2014 Wiley Periodicals, Inc.     

AFM for analysis of structure and dynamics of DNA and protein-DNA complexes

This paper describes protocols for studies of structure and dynamics of DNA and protein-DNA complexes with atomic force microscopy (AFM) utilizing the surface chemistry approach. The necessary specifics for the preparation of functionalized surfaces and AFM probes with the use of silanes and silatranes, including the protocols for synthesis of silatranes are provided. The methodology of studies of local and global conformations DNA with the major focus on the time-lapse imaging of DNA in aqueous solutions is illustrated by the study of dynamics of Holliday junctions including branch migration. The analysis of nucleosome dynamics is selected as an example to illustrate the application of the time-lapse AFM to studies of dynamics of protein-DNA complexes. The force spectroscopy is the modality of AFM with a great importance to various fields of biomedical studies. The AFM force spectroscopy approach for studies of specific protein-DNA complexes is illustrated by the data on analysis of dynamics of synaptic SfiI-DNA complexes. When necessary, additional specifics are added to the corresponding example.     

Topology and life: In search of general mathematical principles in biology and sociology

Mathematical biology has hitherto emphasized the quantitative, metric aspects of the physical manifestations of life, but has neglected the relational or positional aspects, which are of paramount importance in biology. Although, for example, the processes of locomotion, ingestion, and digestion in a human are much more complex than in a protozoan, the general relations between these processes are the same in all organisms. To a set of very complicated digestive functions of a higher animal there correspond a few simple functions in a protozoan. In other words, the more complicated processes in higher organisms can be mapped on the simpler corresponding processes in the lower ones. If any scientific study of this aspect of biology is to be possible at all, there must exist some regularity in such mappings. We are, therefore, led to the following principle: If the relations between various biological functions of an organism are represented geometrically in an appropriate topological space or by an appropriate topological complex, then the spaces or complexes representing different organisms must be obtainable by a proper transformation from one or very fewprimordial spaces or complexes. The appropriate representation of the relations between the different biological functions of an organism appears to be a one-dimensional complex, or graph, which represents the “organization chart” of the organism. The problem then is to find a proper transformation which derives from this graph the graphs of all possible higher organisms. Both a primordial graph and a transformation are suggested and discussed. Theorems are derived which show that the basic principle of mapping and the transformation have a predictive value and are verifiable experimentally. These considerations are extended to relations within animal and human societies and thus indicate the reason for the similarities between some aspects of societies and organisms. It is finally suggested that the relation between physics and biology may lie on a different plane from the one hitherto considered. While physical phenomena are the manifestations of the metric properties of the four-dimensional universe, biological phenomena may perhaps reflect some local topological properties of that universe.     

CHELATOR: an improved method for computing metal ion concentrations in physiological solutions.

An algorithm is presented for the calculation of metal ion concentrations from given total metal concentrations (and vice versa) in physiological media containing metal-chelating compounds. In such media, conditions differ from those used for stability constant determination of metal-chelator equilibria; therefore calculated metal ion concentrations are incorrect. We recompute stability constants to reflect the effects of ionic strength and temperature of physiological solutions. Twelve different equilibria can be considered per metal-chelator pair. The computer program also calculates the contribution of ionized species of metals, chelator, complexes and pH buffers to ionic strength. Measurements with a Ca-selective electrode and with fura-2 show that calculated ionic Ca2+ concentrations are correct from 10 nM up to the millimolar range. The importance of the correct calculation of metal ion concentrations in physiological experiments is demonstrated by data, and derived kinetic parameters, on Na+/Ca2+ exchange and the ATP-dependent Ca2+ pump of enterocyte plasma membrane vesicles. The program is written in Turbo Pascal and will run on IBM-compatible computers. It is menu-driven and supports the use of a Microsoft mouse.     

On the study of plant defence and herbivory using comparative approaches: how important are secondary plant compounds

Species comparisons are a cornerstone of biology and there is a long tradition of using the comparative framework to study the ecology and evolution of plant defensive traits. Early comparative studies led to the hypothesis that plant chemistry plays a central role in plant defence, and the evolution of plant secondary chemistry in response to insect herbivory remains a classic example of coevolution. However, recent comparative work has disagreed with this paradigm, reporting little connection between plant secondary chemicals and herbivory across distantly related plant taxa. One conclusion of this new work is that the importance of secondary chemistry in plant defence may have been generally overstated in earlier research. Here, we attempt to reconcile these contradicting viewpoints on the role of plant chemistry in defence by critically evaluating the use and interpretation of species correlations as a means to study defence–herbivory relationships. We conclude that the notion that plant primary metabolites (e.g. leaf nitrogen content) are the principal determinants of herbivory (or the target of natural selection by herbivores) is not likely to be correct. Despite the inference of recent community‐wide studies of herbivory, strong evidence remains for a prime role of secondary compounds in plant defence against herbivores.     

Tuning the properties of M(diimine)(dithiolate) complexes - The role of the metal and solvent effect. A combined experimental, DFT and TDDFT study

A combined experimental and DFT/TDDFT study on a series of seven M(diimine)(dithiolate) complexes of Group VIII metals has been performed. This analysis focuses mainly on three aspects: (a) the role of the metal, (b) the connection of NLO properties, through the intrinsic hyperpolarizability, with the slope of solvatochromic plots and (c) the effect of solvation on the valence orbitals of the complexes. Besides, the molecular and the electronic structure as well as the bonding scheme of these complexes are also explored. The three aforementioned aspects were not satisfactorily clarified in the literature up to now. Moreover, as it is proved, they possess a central role in the experimental design of the reactions in which these complexes take place or in the design of the synthesis of compounds with pre-required properties.     

A wide family of pyridoxal thiosemicarbazone ferric complexes: Syntheses, structures and magnetic properties

This study reports the syntheses and the characterization of 12 ferric complexes of pyridoxal thiosemicarbazone. The richness of the coordination chemistry of this ligand is highlighted by the modulation of its charge from neutral H₂L to anionic L²⁻, thus leading to a wide family of ferric compounds with charge varying from +3 to −1. The structures of complexes [Fe(HL)₂]ClO₄ · 2H₂O and [Fe(HL)L] · 4.5H₂O were solved and discussed with a particular attention brought to the intermolecular interactions occurring between the complexes. The investigation of magnetic properties of these compounds revealed that two of them are in the HS state at any temperature, whereas the others are in the LS state. These results are discussed in relation to the modulation of the electronic properties of the ligand.     

Electron microscopy for the rapid detection and identification of viruses from clinical specimens

The advantages of using electron microscopy for rapid diagnosis of virus infection from clinical specimens, for identification of virus isolates with unusual properties, and for monitoring endogenous agents in cell cultures are illustrated by several actual cases that have occurred over the years. The importance of using morphological characteristics of viruses for initial identification is emphasized.     

Precipitation, chelation, and the availability of metals as nutrients in anaerobic digestion. II. Applications

The relative importance of the individual effects of precipitation and chelation of metal ions in anaerobic digestion is assessed. Experimentally determined soluble metal ion levels are compared with predicted levels obtained by using a previously described methodology.(1) It is found that soluble metal complexes may increase the level of soluble metals in the presence of CO(3) (2-) and S(2-) by a factor of up to 10(4). The formation of a soluble complex may increase or decrease the availability of the metal ion in question for microbial uptake. Two case studies are presented, one using a defined medium and one a complex medium. It is possible, in the case of the defined medium, to accurately predict the free metal ion concentration using the methodology previously developed.(1) While the identification of the presence of natural chelating compounds in a complex medium is not routinely possible, the significant discrepancy between the measured level of the soluble metal ion Fe(2+) and the calculated level in the case studies presented indicates that natural chelating compounds may play a vital role in providing available metal ions to the microorganisms of an anaerobic digester.     

Copper complexes as therapeutic agents

The importance of transition metals in biological processes has been well established. Copper (Cu) is a transition metal that can exist in oxidised and reduced states. This allows it to participate in redox and catalytic chemistry, making it a suitable cofactor for a diverse range of enzymes and molecules. Cu deficiency or toxicity is implicated in a variety of pathological conditions; therefore inorganic complexes of Cu have been investigated for their therapeutic and diagnostic potential. These Cu complexes have been shown to be effective in cancer treatment due to their cytotoxic action on tumour cells. Alternatively, Cu complexes can also modulate Cu homeostasis in the brain, resulting in protective effects in several models of neurodegeneration. In other diseases such as coronary heart disease and skin disease, the success of Cu complexes as potential therapeutics will most likely be due to their ability to increase SOD activity, leading to relief of oxidative stress. This review seeks to provide a broad insight into some of the diverse actions of Cu complexes and demonstrate the strong future for these compounds as potential therapeutic agents.     

NMR spectroscopy to study the fate of metallodrugs in cells

Metal-based drugs can modulate various biological processes and exhibit a rich variety of properties that foster their use in biomedicine and chemical biology. On the way to intracellular targets, ligand exchange and redox reactions can take place, thus making metallodrug speciation in vivo a challenging task. Advances in NMR spectroscopy have made it possible to move from solution to live-cell studies and elucidate the transport of metallodrugs and interactions with macromolecular targets in a physiological setting. In turn, the electronic properties and supramolecular chemistry of metal complexes can be exploited to characterize drug delivery nanosystems by NMR. The recent evolution of in-cell NMR methodology is presented with special emphasis on metal-related processes. Applications to paradigmatic cases of platinum and gold drugs are highlighted.