In contrast to porphyrins and chlorins, the direct metalation of bacteriochlorins is difficult. Nevertheless, Cu2+ and Zn2+ can be introduced into bacteriopheophytin in acetic acid, whereas Cd2+ can be inserted in dimethylformamide. The former reactions depend on the substituents of the isocyclic ring:  they are facilitated if enolization of the β-ketoester system is inhibited. Starting with [Cd]-bacteriochlorophyll-a or its 132-hydroxy derivative, a series of metallo-bacteriochlorins with central divalent ions Pd2+, Co2+, Ni2+, Cu2+, Zn2+, and Mn2+ have been obtained by transmetalation. Like in the parent Mg complex, the four principal optical transitions are well-separated in these complexes, and their responses to changes in the central metal and its coordination state can be followed in detail. The energies of the Q y and B x transitions are almost independent of the central metal, whereas the Q x and B y transition energies change significantly, depending on the central metal as well as the presence of additional axial ligands. If the complexes are grouped by their coordination number, empirical linear correlations exist between these shifts and the ratio / , where is Pauling's electronegativity value and is the ionic radius of the metal. A similar correlation was found for those 1H NMR signals influenced mainly by the ring current and for the redox potentials. This observation was in contrast with the linear relationships with alone, found for metal-substituted porphyrins. The spectral variations influenced by the central metal and its state of ligation are attributed, within the framework of the four-orbital model, to the electrostatic interaction of the electron densities in the four orbitals with the effective charge of the central metal ions, which is most pronounced for the a2u orbital (HOMO-1). Ligation studies have revealed that addition of the first axial ligand decreases the effective charge of the central metal by approximately 50% and addition of the second axial ligand by another 20% with respect to the absence of axial ligands. The singlet−triplet splitting deduced from fluorescence and phosphorescence measurements is similar for [Pd]-, [Cu]-, [Zn]-, and [Mg]-BChl (4550 ± 100 cm-1).

The role of zinc, an essential element for normal brain function, in the pathology of Alzheimer's disease (AD) is poorly understood. On one hand, physiological and genetic evidence from transgenic mouse models supports its pathogenic role in promoting the deposition of the amyloid beta-protein (Abeta) in senile plaques. On the other hand, levels of extracellular ("free") zinc in the brain, as inferred by the levels of zinc in cerebrospinal fluid, were found to be too low for inducing Abeta aggregation. Remarkably, the release of transient high local concentrations of zinc during rapid synaptic events was reported. The role of such free zinc pulses in promoting Abeta aggregation has never been established. Using a range of time-resolved structural and spectroscopic techniques, we found that zinc, when introduced in millisecond pulses of micromolar concentrations, immediately interacts with Abeta 1-40 and promotes its aggregation. These interactions specifically stabilize non-fibrillar pathogenic related aggregate forms and prevent the formation of Abeta fibrils (more benign species) presumably by interfering with the self-assembly process of Abeta. These in vitro results strongly suggest a significant role for zinc pulses in Abeta pathology. We further propose that by interfering with Abeta self-assembly, which leads to insoluble, non-pathological fibrillar forms, zinc stabilizes transient, harmful amyloid forms. This report argues that zinc represents a class of molecular pathogens that effectively perturb the self-assembly of benign Abeta fibrils, and stabilize harmful non-fibrillar forms.

Decades of research on the physical processes and chemical reaction-pathways in photosynthetic enzymes have resulted in an extensive database of kinetic information. Recently, this database has been augmented by a variety of high and medium resolution crystal structures of key photosynthetic enzymes that now include the two photosystems (PSI and PSII) of oxygenic photosynthetic organisms. Here, we examine the currently available structural and functional information from an engineer's point of view with the long-term goal of reproducing the key features of natural photosystems in de novo designed and custom-built molecular solar energy conversion devices. We find that the basic physics of the transfer processes, namely, the time constraints imposed by the rates of incoming photon flux and the various decay processes allow for a large degree of tolerance in the engineering parameters. Moreover, we find that the requirements to guarantee energy and electron transfer rates that yield high efficiency in natural photosystems are largely met by control of distance between chromophores and redox cofactors. Thus, for projected de novo designed constructions, the control of spatial organization of cofactor molecules within a dense array is initially given priority. Nevertheless, constructions accommodating dense arrays of different cofactors, some well within 1 nm from each other, still presents a significant challenge for protein design.

Antimicrobial activity is being increasingly linked to amyloid fibril formation, suggesting physiological roles for some human amyloids, which have historically been viewed as strictly pathological agents. This work reports on formation of functional cross-α amyloid fibrils of the amphibian antimicrobial peptide uperin 3.5 at atomic resolution, an architecture initially discovered in the bacterial PSMα3 cytotoxin. The fibrils of uperin 3.5 and PSMα3 comprised antiparallel and parallel helical sheets, respectively, recapitulating properties of β-sheets. Uperin 3.5 demonstrated chameleon properties of a secondary structure switch, forming mostly cross-β fibrils in the absence of lipids. Uperin 3.5 helical fibril formation was largely induced by, and formed on, bacterial cells or membrane mimetics, and led to membrane damage and cell death. These findings suggest a regulation mechanism, which includes storage of inactive peptides as well as environmentally induced activation of uperin 3.5, via chameleon cross-α/β amyloid fibrils.

The ability to tune the light-absorption properties of chlorophylls by their protein environment is the key to the robustness and high efficiency of photosynthetic light-harvesting proteins. Unfortunately, the intricacy of the natural complexes makes it very difficult to identify and isolate specific protein-pigment interactions that underlie the spectral-tuning mechanisms. Herein we identify and demonstrate the tuning mechanism of chlorophyll spectra in type II water-soluble chlorophyll binding proteins from Brassicaceae (WSCPs). By comparing the molecular structures of two natural WSCPs we correlate a shift in the chlorophyll red absorption band with deformation of its tetrapyrrole macrocycle that is induced by changing the position of a nearby tryptophan residue. We show by a set of reciprocal point mutations that this change accounts for up to 2/3 of the observed spectral shift between the two natural variants.

Changes in the electronic transition energies and redox potentials because of metal substitution in bacteriochlorophyll a justify the recently suggested correlation between electronegativity χM, covalent radius, and an effective charge, Q M, at the metal atom center. A simple electrostatic theory in which Q M modifies the energies of the frontier molecular orbitals by Coulombic interactions with the charge densities at the atomic π centers is suggested. The relative change in electrostatic potential at a distance r a from the metal center is ΔQ M/r a, where ΔQ M, the change in the metal effective positive charge because of Mg being substituted by another metal, varies with the change in metal electronegativity (Mulliken's values) ΔχM and covalent radius Δ . ΔQ M consists of two components:  the major component, Δ , characteristic of the central metal, is independent of the molecular environment and proportional to the electronegativity of the metal at a typical valence state. The second component, Δq M,N, reflects those perturbations induced by the molecular frame. It depends on the overlap between the metal and ligand orbitals hence changes both with the metal covalent radius (i.e., its typical “size”) and the particular orbital environment. For the series of metals that we examined, we determined that Δ = (0.12 ± 0.02) ΔχM. Significant contributions of Δq M,N to ΔQ M,N were found for the changes in the energies of the y-polarized electronic transitions B y and Q y and to a lesser extent the first oxidation potential . Minor contributions were found for the changes in the energies of the x-polarized electronic transitions B x and Q x and the first reduction potential . The model agrees well with target testing factor analysis performed on the entire data space. Simulations of the experimental redox potentials and the four electronic transitions required mixing of single-electron promotions; however, the coefficients for the configuration interactions were assumed to be metal-independent within the examined series because the relative oscillator strengths of the various transitions did not show significant changes upon metal substitution. The reported observations and the accompanying calculations provide experimental support to the modern concepts of electronegativity and may help in better understanding biological redox centers consisting of porphyrins or chlorophylls.

Understanding how specific protein environments affect the mechanisms of non-radiative energy dissipation within densely assembled chlorophylls in photosynthetic protein complexes is of great interest to the construction of bioinspired solar energy conversion devices. Mixing of charge-transfer and excitonic states in excitonically interacting chlorophylls was implicated in shortening excited states lifetimes but its relevance to active control of energy dissipation in natural systems is under considerable debate. Here we show that the degree of fluorescence quenching in two similar pairs of excitonically interacting bacteriochlorophyll derivatives is directly associated with increasing charge transfer character in the excited state, and that the protein environment may control non-radiative dissipation by affecting the mixing of charge transfer and excitonic states. The capability of local protein environments to determine the fate of excited states, and thereby to confer different functionalities to excitonically coupled dimers substantiates the dimer as the basic functional element of photosynthetic enzymes.

We show that a single internal polar interaction per helix is sufficient to engender structural specificity in that helix in helical bundle proteins. Furthermore, we use histidine-binding cofactors of different shapes which bind directly into the core, demonstrating that this structural specificity is not the result of a prescribed complimentary, "knobs in holes" core packing. We show that we can switch structural specificity of individual helices on and off by ligating cofactors, singly and in pairs, which bind either one or two histidine ligands. To our knowledge, this is the first demonstration of such extensive manipulation of protein structure by ligand binding, an important result of general interest to those working with self-assembled molecular systems. Finally, as these proteins were designed without the use of computational modeling, we not only demonstrate that designing a uniquely structured cofactor binding protein is not as difficult as is generally believed, we have determined why this is so: hydrophobic core complementarity, which is very difficult to design, is not necessary. Instead, a much simpler design process entails the creation of core polar interactions which themselves can drive conformational specificity.