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Thirteen boronated cyanometallates [M(CN-BR

Long-range electron tunneling through metalloproteins is facilitated by evolutionary tuning of donor-acceptor electronic couplings, formal electrochemical potentials, and active-site reorganization energies. Although the minimal frustration of the folding landscape enables this tuning, residual frustration in the vicinity of the metallocofactor can allow conformational fluctuations required for protein function. We show here that the constrained copper site in wild-type azurin is governed by an intricate pattern of minimally frustrated local and distant interactions that together enable rapid electron flow to and from the protein. In contrast, sluggish electron transfer reactions (unfavorable reorganization energies) of active-site azurin variants are attributable to increased frustration near to as well as distant from the copper site, along with an exaggerated oxidation-state dependence of both minimally and highly frustrated interaction patterns.

Hotly debated these days is whether nickel or iron is the active site in nickel–iron water oxidation electrocatalysts. We have previously argued that iron is a likely candidate for highly active materials because it can reach high-oxidation (high-ox) states at potentials relevant to water splitting. Here, we further assert that nickel is likely not an active site for water oxidation electrocatalysis in these materials. Our 3-fold argument is supported by electrochemical measurements on rigorously planar electrodes produced by pulsed laser ablation in liquids: (1) nickel cannot achieve high-ox states in aqueous environments at relevant potentials; (2) large steady-state concentrations of metal sites preclude them from being active, thereby indicating that even more oxidizing moieties are critically important; and (3) unlike nickel sites, high-ox iron sites documented experimentally are neither rare nor unreasonably reactive.

We have investigated the roles of tyrosine (Tyr) and tryptophan (Trp) residues in the four-electron reduction of oxygen catalyzed by

Flavocytochrome P450 from Bacillus megaterium (P450

Chlorophyll special pairs in photosynthetic reaction centers function as both exciton acceptors and primary electron donors. Although the macrocyclic natural pigments contain Mg(II), the central metal in most synthetic analogs is Zn(II). Here we report that insertion of either Al(III) or Ga(III) into an imidazole-substituted corrole affords an exceptionally robust photoactive dimer. Notably, attractive electronic interactions between dimer subunits are relatively strong, as documented by signature changes in NMR and electronic absorption spectra, as well as by cyclic voltammetry, where two well-separated reversible redox couples were observed. EPR spectra of one-electron oxidized dimers closely mimic those of native special pairs, and strong through-space interactions between corrole subunits inferred from spectroscopic and electrochemical data are further supported by crystal structure analyses (3 Å interplanar distances, 5 Å lateral shifts, and 6 Å metal to metal distances).

Manganese ([Mn(CO)3]) and rhenium tricarbonyl ([Re(CO)3]) complexes represent a workhorse family of compounds with applications in a variety of fields. Here, the coordination, structural, and electrochemical properties of a family of mono- and bimetallic [Mn(CO)3] and [Re(CO)3] complexes are explored. In particular, a novel heterobimetallic complex featuring both [Mn(CO)3] and [Re(CO)3] units supported by 2,2′-bipyrimidine (bpm) has been synthesized, structurally characterized, and compared to the analogous monomeric and homobimetallic complexes. To enable a comprehensive structural analysis for the series of complexes, we have carried out new single crystal X-ray diffraction studies of seven compounds: Re(CO)3Cl(bpm), anti-[{Re(CO3)Cl}2(bpm)], Mn(CO)3Br(bpz) (bpz = 2,2′-bipyrazine), Mn(CO)3Br(bpm), syn- and anti-[{Mn(CO3)Br}2(bpm)], and syn-[Mn(CO3)Br(bpm)Re(CO)3Br]. Electrochemical studies reveal that the bimetallic complexes are reduced at much more positive potentials (ΔE ≥ 380 mV) compared to their monometallic analogues. This redox behavior is consistent with introduction of the second tricarbonyl unit which inductively withdraws electron density from the bridging, redox-active bpm ligand, resulting in more positive reduction potentials. [Re(CO3)Cl]2(bpm) was reduced with cobaltocene; the electron paramagnetic resonance spectrum of the product exhibits an isotropic signal (near g = 2) characteristic of a ligand-centered bpm radical. Our findings highlight the facile synthesis as well as the structural characteristics and unique electrochemical behavior of this family of complexes.

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents para to the isocyanide functionality results in W(CNDippAr)₆ oligoarylisocyanide complexes with greatly enhanced metal-to-ligand charge transfer (MLCT) excited-state properties relative to those of W(CNDipp)₆. Extending electronic modifications to delineate additional design principles for this class of photosensitizers, herein we report a series of W(CNAr)₆ compounds with naphthalene-based fused-ring (CN-1-(2-ⁱPr)-Naph) and CNDipp-based alkynyl-bridged (CNDipp^(CC)Ar) arylisocyanide ligands. Systematic variation of the secondary aromatic system in the CNDippCCAr platform provides a straightforward method to modulate the photophysical properties of W(CNDipp^(CC)Ar)₆ complexes, allowing access to an extended range of absorption/luminescence profiles and highly reducing excited states, while maintaining the high molar absorptivity MLCT absorption bands, high photoluminescence quantum yields, and long excited-state lifetimes of previous W(CNAr)₆ complexes. Notably, W(CN-1-(2-iPr)-Naph)₆ exhibits the longest excited-state lifetime of all W(CNAr)₆ complexes explored thus far, highlighting the potential benefits of utilizing fused-ring arylisocyanide ligands in the construction of tungsten(0) photoreductants.

Manganese-enhanced magnetic resonance imaging (MEMRI) holds exceptional promise for preclinical studies of brain-wide physiology in awake-behaving animals. The objectives of this review are to update the current information regarding MEMRI and to inform new investigators as to its potential. Mn(II) is a powerful contrast agent for two main reasons: (1) high signal intensity at low doses; and (2) biological interactions, such as projection tracing and neural activity mapping via entry into electrically active neurons in the living brain. High-spin Mn(II) reduces the relaxation time of water protons: at Mn(II) concentrations typically encountered in MEMRI, robust hyperintensity is obtained without adverse effects. By selectively entering neurons through voltage-gated calcium channels, Mn(II) highlights active neurons. Safe doses may be repeated over weeks to allow for longitudinal imaging of brain-wide dynamics in the same individual across time. When delivered by stereotactic intracerebral injection, Mn(II) enters active neurons at the injection site and then travels inside axons for long distances, tracing neuronal projection anatomy. Rates of axonal transport within the brain were measured for the first time in "time-lapse" MEMRI. When delivered systemically, Mn(II) enters active neurons throughout the brain via voltage-sensitive calcium channels and clears slowly. Thus behavior can be monitored during Mn(II) uptake and hyperintense signals due to Mn(II) uptake captured retrospectively, allowing pairing of behavior with neural activity maps for the first time. Here we review critical information gained from MEMRI projection mapping about human neuropsychological disorders. We then discuss results from neural activity mapping from systemic Mn(II) imaged longitudinally that have illuminated development of the tonotopic map in the inferior colliculus as well as brain-wide responses to acute threat and how it evolves over time. MEMRI posed specific challenges for image data analysis that have recently been transcended. We predict a bright future for longitudinal MEMRI in pursuit of solutions to the brain-behavior mystery.

Complexes with the formula [M(diimine)(CN-BR3)4]2–, where diimine = bipyridine (bpy), phenanthroline (phen), 3,5-trifluoromethylbipyridine (flpy), R = Ph, C6F5, and M = FeII, RuII, were synthesized...

Ammonia (NH₃) is essential for food production and is commercially synthesized from nitrogen (N₂) and hydrogen (H₂) using the Haber–Bosch process. Enormous amounts of ammonia are made every year in a reaction that requires high temperatures and pressures, with the Haber–Bosch accounting for ∼1.6% of total annual global energy consumption. Electrocatalysts are also being explored to convert in an environmentally friendly manner N₂ to NH₃ at ambient temperature and pressure.

Separate focus on the oligomerization and oxidative cyclization steps required for the synthesis of 5,10,15-tris(trifluoromethyl)corrole revealed [bis(trifluoroacetoxy)iodo]benzene (PIFA) as a superior alternative oxidant. Under optimized conditions, the pure free-base corrole was obtained with a 6-fold increase in chemical yield and an 11-fold rise in isolated material per synthesis. The corresponding gallium(III) and manganese(III) complexes were isolated by adding the appropriate metal salt prior to corrole purification.

High-potential iron-oxo species are intermediates in the catalytic cycles of oxygenase enzymes. They can cause heme degradation and irreversible oxidation of nearby amino acids. We have proposed that there are protective mechanisms in which hole hopping from oxidized hemes through tryptophan/tyrosine chains generates a surface-exposed amino-acid oxidant that could be rapidly disarmed by reaction with cellular reductants. In investigations of cytochrome P450BM3, we identified Trp96 as a critical residue that could play such a protective role. This Trp is cation-πpaired with Arg398 in 81% of mammalian P450s. Here we report on the effect of the Trp/Arg cation-πinteraction on Trp96 formal potentials as well as on electronic coupling strengths between Trp96 and the heme both for wild type cytochrome P450 and selected mutants. Mutation of Arg398 to His, which decreases the Trp96 formal potential, increases Trp-heme electronic coupling; however, surprisingly, the rate of phototriggered electron transfer from a Ru-sensitizer (through Trp96) to the P450BM3 heme was unaffected by the Arg398His mutation. We conclude that Trp96 has moved away from Arg398, suggesting that the protective mechanism for P450s with this Trp-Arg pair is conformationally gated.

Electrocatalytic reduction of dinitrogen (N2) to ammonium (NH4+) in acidic aqueous solutions was investigated at ambient temperature and pressure using a cobalt–molybdenum (CoMo) thin-film electrode prepared by magnetron reactive sputtering. Increased concentrations of ammonium ions (NH4+) were consistently detected in the electrolyte using ion chromatography (IC) after constant-potential electrolysis at various potentials (≤−0.29 V vs. RHE). Using a newly developed analytical method based on ammonia derivatization, performing the experiments with 15N2-labelled gas led however to the detection of increased 14NH4+ concentrations instead of 15NH4+. X-ray photoelectron spectroscopic (XPS) analysis of the electrode surface revealed the presence of Mo[triple bond, length as m-dash]N and Mo–NHx species. Several contamination sources were identified that led to substantial increases in the concentration of ammonium ions, including 15NH3 impurities in 15N2 gas. The observed ammonium concentrations can be consistently ascribed to leaching of nitrogen (14N) impurities incorporated in the CoMo film during the sputtering process. Researchers in the field are therefore urged to adopt extended protocols to identify and eliminate sources of ammonia contamination and to very carefully monitor the ammonium concentrations in each experimental step.\ud \ud

Iron-doped nickel layered double hydroxides (LDHs) are among the most active heterogeneous water oxidation catalysts. Due to interspin interactions, however, the high density of magnetic centers results in line-broadening in magnetic resonance spectra. As a result, gaining atomic-level insight into the catalytic mechanism via electron paramagnetic resonance (EPR) is not generally possible. To circumvent spin-spin broadening, iron and nickel atoms were doped into nonmagnetic [ZnAl]-LDH materials and the coordination environments of the isolated Fe(III) and Ni(II) sites were characterized. Multifrequency EPR spectroscopy identified two distinct Fe(III) sites (S = 5/2) in [Fe:ZnAl]-LDH. Changes in zero field splitting (ZFS) were induced by dehydration of the material, revealing that one of the Fe(III) sites was solvent-exposed (i.e., at an edge, corner, or defect site). These solvent-exposed sites featured an axial ZFS of 0.21 cm-1 when hydrated. The ZFS increased dramatically upon dehydration (to -1.5 cm-1), owing to lower symmetry and a decrease in the coordination number of iron. The ZFS of the other ("inert") Fe(III) site maintained an axial ZFS of 0.19-0.20 cm-1 under both hydrated and dehydrated conditions. We observed a similar effect in [Ni:ZnAl]-LDH materials; notably, Ni(II) (S = 1) atoms displayed a single, small ZFS (±0.30 cm-1) in hydrated material, whereas two distinct Ni(II) ZFS values (±0.30 and ±1.1 cm-1) were observed in the dehydrated samples. Although the magnetically dilute materials were not active catalysts, the identification of model sites in which the coordination environments of iron and nickel were particularly labile (e.g., by simple vacuum drying) is an important step toward identifying sites in which the coordination number may drop spontaneously in water, a probable mechanism of water oxidation in functional materials.

W(CNAr)₆ (CNAr = arylisocyanide) photoreductants catalyze base-promoted homolytic aromatic substitution (BHAS) of 1-(2-iodobenzyl)-pyrrole in deuterated benzene. Moderate to high efficiencies correlate with W(CNAr)₆ excited-state reduction potentials upon one-photon 445 nm excitation, with 10 mol % loading of the most powerful photoreductants W(CNDipp)₆ (CNDipp = 2,6-diisopropylphenylisocyanide) and W(CNDippPh^(OMe3))6 (CNDippPh^(OMe3) = 4-(3,4,5-trimethoxyphenyl)-2,6-diisopropylphenylisocyanide) affording nearly complete conversion. Stern–Volmer quenching experiments indicated that catalysis is triggered by substrate reductive dehalogenation. Taking advantage of the large two-photon absorption (TPA) cross sections of W(CNAr)₆ complexes, we found that photocatalysis can be driven with femtosecond-pulsed 810 nm excitation. For both one- and two-photon excitation, photocatalysis was terminated by the formation of seven-coordinate WII-diiodo [WI₂(CNAr)₅] complexes. Notably, we discovered that W(CNDipp)₆ can be regenerated by chemical reduction of WI2(CNDipp)5 with excess ligand present in solution.

Tetracyanonickelate(II) has been a poster child of ligand field theory for several decades. We have revisited the literature assignments of the absorption spectrum of [Ni(CN) ₄]²⁻ and the calculated ordering of orbitals with metal d character. Using low-temperature single-crystal absorption spectroscopy and accurate ab initio and density functional quantum mechanical methods (NEVPT2-CASSCF, EOM-CCSD, TD-DFT), we find an ordering of the frontier d- and p-orbitals of xy < xz, yz < z² < z < x²–y² < x, y and assign the d-d bands in the absorption spectrum to ¹A_(1g) → ³B_(1g) < ³E_g < ³A_(2g) < ¹B_(1g) < ¹E_g < ¹A_(2g). While differing from all previous interpretations, our assignments accord with an MO model in which strong π-backbonding in the plane of the molecule stabilizes d_(xy) more than out-of-plane bonding stabilizes d_(xz) and d_(yz).

In aqueous media, hydrophobic metallocorroles form nanoparticles that are potential theranostic anticancer agents. We have analyzed the electronic and Raman spectra of Al(III), Ga(III), and Au(III) corrole nanoparticles (and made comparisons with DFT-validated assignments of the IR spectra of corresponding monomers) in order to estimate the strengths of corrole-corrole electronic couplings in these assemblies. We find that these spectra are virtually unchanged upon aggregation, confirming that the intermolecular interactions in these nanoparticles are very weak.

Electron flow through proteins is a crucial factor, which decides about their multiple functions in living organisms. Incorporating polypeptides as bridges in donor-bridge-acceptor (DBA) conjugates allows for examining how various structural features in proteins affect the kinetics of the CT processes they mediate. Based on the premise that hydrogen-bonds formation could serve to modify geometry and special orientation of donor and acceptor scaffolds in covalently linked bichromophoric system we designed and synthesized series of dyads comprised of perylene-bisimide and free-base corrole. Specifically, the object of the study was hydrogen-bonded discrete assemblies of corroles possessing core-NH as hydrogen bond donor and amide groups located at position meso-10 as hydrogen bond acceptor. The three dyads differ in type and number of bridging aminoacids’ moieties: L-alanine and L-phenylalanine and one or four respectively. These complex corroles were prepared via synthesis of perylenebisimide-amino acid conjugate possessing free NH2 group followed by amidation of COOH-corrole. Combined steady-state and time-resolved photophysical studies identified that electron-transfer occurs in all four bichromophoric systems. Our focus was on alanine tetramer that is long enough not to mediate too efficiently through-bond CT. A corrole moiety serves as an electron donor, and a perylenediimide as an acceptor. The picosecond rates of electron transfer suggests that the electronic-coupling pathways cannot be through-bond and most likely involve through-hydrogen bond interaction. References Orłowski, R.; Vakuliuk, O.; Gullo, M. P.; Danylyuk, O.; Ventura, B.; Koszarna, B.; Tarnowska, A.; Jaworska, N.; Barbieri, A.; Gryko, D. T. Commun. 2015, 51, 8284-8287. Orłowski, R.; Cichowicz, G.; Staszewska-Krajewska, O.; Schilf, W.; Cyrański, M. K.; Gryko, D. T. Eur. J. 2019, 25, 9658-9664. Figure 1

Reactions of α- and β-diimine quinoline aldoximes with Mn(I) and Re(I) tricarbonyl halides afford quinoline oxime complexes. Both Mn(I) and Re(I) complexes experience severe geometric strain due to ligand steric interactions: 6-membered metallocycles exhibit more pronounced distortions than 5-membered ones, consistent with density functional theory structural analyses. Such distortions likely also affect reactivity patterns, as evidenced by Re(I)-induced deoximation of a quinoline variant containing a CF_3-ketoxime.

The steady-state charge and spin transfer yields were measured for three different Ru-modified azurin derivatives in protein films on silver electrodes. While the charge-transfer yields exhibit weak temperature dependences, consistent with operation of a near activation-less mechanism, the spin selectivity of the electron transfer improves as temperature increases. This enhancement of spin selectivity with temperature is explained by a vibrationally induced spin exchange interaction between the Cu(II) and its chiral ligands. These results indicate that distinct mechanisms control charge and spin transfer within proteins. As with electron charge transfer, proteins deliver polarized electron spins with a yield that depends on the protein’s structure. This finding suggests a new role for protein structure in biochemical redox processes.

The attachment of the 2,2′-bipyridine (bpy) moieties to the surface of planar silicon(111) (photo)electrodes was investigated using ab initio simulations performed on a new cluster model for methyl-terminated silicon. Density functional theory (B3LYP) with implicit solvation techniques indicated that adventitious chlorine atoms, when present in the organic linker backbone, led to instability at very negative potentials of the surface-modified electrode. In prior experimental work, chlorine atoms were present as a trace surface impurity due to required surface processing chemistry, and thus could plausibly result in the observed surface instability of the linker. Free energy calculations for the Cl-atom release process with model silyl-linker constructs revealed a modest barrier (14.9 kcal mol−1) that decreased as the electrode potential became more negative. A small library of new bpy-derived structures has additionally been explored computationally to identify strategies that could minimize chlorine-induced linker instability. Structures with fluorine substituents are predicted to be more stable than their chlorine analogues, whereas fully non-halogenated structures are predicted to exhibit the highest stability. The behavior of a hydrogen-evolving molecular catalyst Cp*Rh(bpy) (Cp* = pentamethylcyclopentadienyl) immobilized on a silicon(111) cluster was explored theoretically to evaluate differences between the homogeneous and surface-attached behavior of this species in a tautomerization reaction observed under reductive conditions for catalytic H2 evolution. The calculated free energy difference between the tautomers is small, hence the results suggest that use of reductively stable linkers can enable robust attachment of catalysts while maintaining chemical behavior on the electrode similar to that exhibited in homogeneous solution.

Hole hopping through tryptophan/tyrosine chains enables rapid unidirectional charge transport over long distances. We have elucidated structural and dynamical factors controlling hopping speed and efficiency in two modified azurin constructs that include a rhenium(I) sensitizer, Re(His)(CO)(3)(dmp)(+), and one or two tryptophans (W(1), W(2)). Experimental kinetics investigations showed that the two closely spaced (3 to 4 Å) intervening tryptophans dramatically accelerated long-range electron transfer (ET) from Cu(I) to the photoexcited sensitizer. In our theoretical work, we found that time-dependent density-functional theory (TDDFT) quantum mechanics/molecular mechanics/molecular dynamics (QM/MM/MD) trajectories of low-lying triplet excited states of Re(I)(His)(CO)(3)(dmp)(+)–W(1)(–W(2)) exhibited crossings between sensitizer-localized (*Re) and charge-separated [Re(I)(His)(CO)(3)(dmp(•–))/(W(1)(•+) or W(2)(•+))] (CS1 or CS2) states. Our analysis revealed that the distances, angles, and mutual orientations of ET-active cofactors fluctuate in a relatively narrow range in which the cofactors are strongly coupled, enabling adiabatic ET. Water-dominated electrostatic field fluctuations bring *Re and CS1 states to a crossing where *Re(CO)(3)(dmp)(+)←W(1) ET occurs, and CS1 becomes the lowest triplet state. ET is promoted by solvation dynamics around *Re(CO)(3)(dmp)(+)(W(1)); and CS1 is stabilized by Re(dmp(•–))/W(1)(•+) electron/hole interaction and enhanced W(1)(•+) solvation. The second hop, W(1)(•+)←W(2), is facilitated by water fluctuations near the W(1)/W(2) unit, taking place when the electrostatic potential at W(2) drops well below that at W(1)(•+). Insufficient solvation and reorganization around W(2) make W(1)(•+)←W(2) ET endergonic, shifting the equilibrium toward W(1)(•+) and decreasing the charge-separation yield. We suggest that multiscale TDDFT/MM/MD is a suitable technique to model the simultaneous evolution of photogenerated excited-state manifolds.

Elucidating the factors that control charge transfer rates in relatively flexible conjugates is of importance for understanding energy flows in biology as well as assisting the design and construction of electronic devices. Here, we report ultrafast electron transfer (ET) and hole transfer (HT) between a corrole (Cor) donor linked to a perylene-diimide (PDI) acceptor by a tetrameric alanine (Ala)(4). Selective photoexcitation of the donor and acceptor triggers subpicosecond and picosecond ET and HT. Replacement of the (Ala)(4) linker with either a single alanine or phenylalanine does not substantially affect the ET and HT kinetics. We infer that electronic coupling in these reactions is not mediated by tetrapeptide backbone nor by direct donor–acceptor interactions. Employing a combination of NMR, circular dichroism, and computational studies, we show that intramolecular hydrogen bonding brings the donor and the acceptor into proximity in a “scorpion-shaped” molecular architecture, thereby accounting for the unusually high ET and HT rates. Photoinduced charge transfer relies on a (Cor)NH(…)O=C–NH(…)O=C(PDI) electronic-coupling pathway involving two pivotal hydrogen bonds and a central amide group as a mediator. Our work provides guidelines for construction of effective donor–acceptor assemblies linked by long flexible bridges as well as insights into structural motifs for mediating ET and HT in proteins.

Manganese ([Mn(CO)(3)]) and rhenium tricarbonyl ([Re(CO)(3)]) complexes represent a workhorse family of compounds with applications in a variety of fields. Here, the coordination, structural, and electrochemical properties of a family of mono- and bimetallic [Mn(CO)(3)] and [Re(CO)(3)] complexes are explored. In particular, a novel heterobimetallic complex featuring both [Mn(CO)(3)] and [Re(CO)(3)] units supported by 2,2′-bipyrimidine (bpm) has been synthesized, structurally characterized, and compared to the analogous monomeric and homobimetallic complexes. To enable a comprehensive structural analysis for the series of complexes, we have carried out new single crystal X-ray diffraction studies of seven compounds: Re(CO)(3)Cl(bpm), anti-[{Re(CO(3))Cl}(2)(bpm)], Mn(CO)(3)Br(bpz) (bpz = 2,2′-bipyrazine), Mn(CO)(3)Br(bpm), syn- and anti-[{Mn(CO(3))Br}(2)(bpm)], and syn-[Mn(CO(3))Br(bpm)Re(CO)(3)Br]). Electrochemical studies reveal that the bimetallic complexes are reduced at much more positive potentials (ΔE ≥ 380 mV) compared to their monometallic analogues. This redox behavior is consistent with introduction of the second tricarbonyl unit which inductively withdraws electron density from the bridging, redox-active bpm ligand, resulting in more positive reduction potentials. [Re(CO(3))Cl](2)(bpm) was reduced with cobaltocene; the electron paramagnetic resonance spectrum of the product exhibits an isotropic signal (near g = 2) characteristic of a ligand-centered bpm radical. Our findings highlight the facile synthesis as well as the structural characteristics and unique electrochemical behavior of this family of complexes.

I first met Bill in the spring of 1965. My good friend George Hammond had told me that Bill was terrific and I should hang out with him.

In an important advance in our understanding of protein folding, Wolynes and Onuchic found that the frustration ratio, T(f) /T(s), for funneled energy Landscapes is T(f) /T(s) ~ 1.6. In recent work on four heme proteins, we showed that when a protein unfolds from the native state to an early unfolded state, the degree of departure is characterized by a ratio f ~ 1.6, where f is a measure of the elongation of n-residue segments of the polypeptide chain. Our analysis, which accounts for this apparent similarity in calculated signatures, is based on a logistic-map model of unfolding. We offer an important take home for the de novo protein synthesis community: in order to increase the probability of obtaining good quality crystals, nearest-neighbor repulsive interactions between adjacent residues (or sequences of residues) in the polypeptide chain must be propagated correctly.

Homoleptic tungsten(0) arylisocyanides possess photophysical and photochemical properties that rival those of archetypal ruthenium(II) and iridium(III) polypyridine complexes. Previous studies established that extending the π-system of 2,6-diisopropylphenylisocyanide (CNDipp) by coupling aryl substituents

We have investigated the structural stability of the SARS-CoV-2 main protease monomer (Mpro). We quantified the spatial and angular changes in the structure using two independent analyses, one based on a spatial metrics (δ, ratio), the second on angular metrics. The order of unfolding of the 10 helices in Mpro is characterized by beta vs alpha plots similar to those of cytochromes and globins. The longest turning region is anomalous in the earliest stage of unfolding. In an investigation of excluded-volume effects, we found that the maximum spread in average molecular-volume values for Mpro, cytochrome c-b562, cytochrome c’, myoglobin, and cytoglobin is ~10 Å3. This apparent universality is a consequence dominant contributions from six residues: ALA, ASP, GLU, LEU, LYS and VAL. Of the seven Mpro histidines, residues 41, 163, 164, and 246 are in stable H-bonded regions; metal ion binding to one or more of these residues could break up the H-bond network, thereby affecting protease function. Our analysis also indicated that metal binding to cysteine residues 44 and 145 could disable the enzyme., Graphical abstract The main protease is a homodimer that cuts polyproteins into functional pieces for the production of new virons. Can metal ions inhibit this enzyme?Unlabelled Image, Highlights • Excluded volume in the folded SARS-CoV-2 main protease is estimated. • Helix stabilities in the SARS-CoV-2 main protease differ dramatically. • Metal ion binding could inhibit the SARS-CoV-2 main protease.

We have analyzed the early stages of unfolding of cytochromes c-b562 (PDB ID: 2BC5) and Rd apo b562 (PDB ID: 1YYJ). Our geometrical approach proceeds from an analysis of the crystal structure reported for each protein. We quantify, residue-by-residue and region-by-region, the spatial and angular changes in the structure as the protein denatures, and quantify differences that result from the seven residues that differ in the two proteins. Using two independent analyses, one based on spatial metrics and the second on angular metrics, we establish the order of unfolding of the five helices in cyt c-b562 and the four helices in the apo protein. For the two helices nearest the N-terminal end of both proteins, the ones in the apo protein unfold first. For the two helices nearest the C-terminal end, the interior helix of the apo protein unfolds first, whereas the terminal helix of the holo protein unfolds first. Excluded-volume effects (repulsive interactions) are minimized in turning regions; the overall range in Δ values is Δ = 36.3 A3 for cyt c-b562 and Δ = 36.6 A3 for the apo protein, whereas the span for all 20 amino acids is Δ = 167.7 A3. As our work indicates that the interior helix of cytochrome c-b562 is the first to fold, we suggest that this helix protects the heme from misligation, consistent with ultrafast folding over a minimally frustrated funneled landscape.

In an analysis of the structural stability of the coronavirus main protease (Mpro), we identified regions of the protein that could be disabled by cobalt(III)-cation binding to histidines and cysteines [1]. Here we have extended our work to include copper(II) chelates, which we have docked to HIS 41 and CYS 145 in the Mpro active-site region. We have found stable docked structures where Cu(II) could readily bond to the CYS 145 thiolate, which would be lethal to the enzyme. We also started studying the Spike Protein, PDB ID: 6VXX and the region around the D614G mutant.

We have investigated the roles of tyrosine (Tyr) and tryptophan (Trp) residues in the four-electron reduction of oxygen catalyzed by Streptomyces coelicolor laccase (SLAC). During normal enzymatic turnover in laccases, reducing equivalents are delivered to a type 1 Cu center (CuT1) and then are transferred over 13 Å to a trinuclear Cu site (TNC: (CuT3)2CuT2) where O2 reduction occurs. The TNC in SLAC is surrounded by a large cluster of Tyr and Trp residues that can provide reducing equivalents when the normal flow of electrons is disrupted. Canters and coworkers have shown that when O2 reacts with a reduced SLAC variant lacking the CuT1 center, a Tyr108· radical near the TNC forms rapidly. We have found that ascorbate reduces the Tyr108· radical in wild-type SLAC about 10 times faster than it reacts with the CuT12+ center, possibly owing to radical transfer along a Tyr/Trp chain. Aerobic oxidation of two reduced SLAC mutants (Y108F and W132F) leads to the formation of a long-lived (~15 min) Tyr· radical with distinct absorption at 408 nm. The diffusion of redox equivalents away from the primary enzymatic pathway in SLAC may indicate a poorly optimized enzyme or a mechanism to protect against protein damage.

Development of novel therapeutic strategies to eradicate malignant tumors is of paramount importance in cancer research. In a recent study, we have introduced a facile protocol for the preparation of corrole-protein nanoparticles (NPs). These NPs consist of a corrole-core coated with protein. We now report that a novel lipophilic corrole, (2)Ga, delivered as human serum albumin (HSA)-coated NPs, displayed antineoplastic activity towards human prostate cancer DU-145 cells. Cryo-TEM analysis of these NPs revealed an average diameter of 50.2 ± 8.1 nm with a spherical architecture exhibiting low polydispersity. In vitro cellular uptake of (2)Ga/albumin NPs was attributable to rapid internalization of the corrole through ligand binding-dependent extracellular release and intercalation of the corrole cargo into the lipid bilayer of the plasma membrane. This finding is in contrast with a previously reported study on corrole-protein NPs that displayed cellular uptake via endocytosis. Investigation of the non-light-induced mechanism of action of (2)Ga suggested the induction of necrosis through plasma membrane destabilization, impairment of calcium homeostasis, lysosomal stress and rupture, as well as formation of reactive oxygen species (ROS). (2)Ga also exhibited potent light-induced cytotoxicity through ROS generation. These findings demonstrate a rapid cellular uptake of (2)Ga/protein NPs along with targeted induction of tumor cell necrosis.

Complexes with the formula [M(diimine)(CN-BR

An Arthur M. Sackler Colloquium titled “Status and Challenges in Science for Decarbonizing our Energy Landscape” was held at the Arnold and Mabel Beckman Center in Irvine, California in October 2018. The papers that follow in this issue of PNAS (1⇓⇓⇓⇓⇓–7) stem from that activity, which addressed a topic of compelling interest and importance to our community from a perspective often not addressed. It is evermore clear, based on incontrovertible climate evidence, that the way we produce and use energy must transition rapidly from what we have done in the past. Population growth, urbanization, and the need for both energy and materials to support this evolution has led to environmental alteration that can only be explained by human activity. As the Intergovernmental Panel on Climate Change and others have emphasized over the last several decades, the average annual temperature of planet Earth has been increasing with greater annual increments. The origin of the increase and its consequences are the greater amounts of CO2 in the atmosphere from approximately 284 parts per million at the start of the industrial revolution to 316 parts per million in 1956, when detailed records were initiated, to 415 parts per million in 2018 (8⇓⇓⇓–12). The well-known “greenhouse” gas effect of CO2 for trapping heat has been described in detail and extends to other polyatomic molecules, such as methane, that are present in much smaller amounts (although their respective greenhouse gas effects may be greater on a molecular basis). The … [↵][1]1To whom correspondence may be addressed. Email: eisenberg{at}chem.rochester.edu. [1]: #xref-corresp-1-1

This century will witness a major transformation in how energy is acquired, stored, and utilized globally. The impetus for this change comes from the deep impacts that both developed and developing societies have had on our planet’s environment during the past century, and the projections going forward of what will happen if we do not act transformatively within the next 2 decades. This paper describes the basis for a meeting held in October 2018 on the need for decarbonization in our energy landscape, and specifically the status and challenges of the science that provides the foundation for such technology. Within the realm of decarbonization in energy generation lies the science of solar energy conversion using new or improved photovoltaic materials and artificial photosynthesis for water splitting and other energy-storing reactions. The intimately related issue of renewable energy storage is being addressed with new strategies, materials, and approaches under current investigation and development. The need to improve the interactions between scientists working on these connected but separately considered challenges and on the transition of scientific achievement to practical application was also addressed, with specific efforts enumerated.

While the icosahedral closo-[B12H12]2– cluster does not display reversible electrochemical behavior, perfunctionalization of this species via substitution of all twelve B–H vertices with alkoxy orbenzyloxy (OR) substituents engenders reversible redox chemistry, providing access to clusters in the dianionic,monoanionic, and neutral forms. Here, we evaluated the electrochemical behavior of the electron-rich B12(O-3-methylbutyl)12 (1) cluster and discovered that a new reversible redox event that gives rise to a fourth electronic state is accessible through one-electron oxidation of the neutral species. Chemical oxidation of 1 with [N(2,4-Br2C6H3)3]•+ afforded the isolable[1] •+ cluster, which is the first example of an open-shell cationic B12 cluster in which the unpaired electron is proposed to be delocalized throughout the boron cluster core. The oxidation of 1 is also chemically reversible, where treatment of [1]•+ with ferrocene resulted in its reduction back to 1. The identity of [1]•+ is supported by EPR, UV-vis, multinuclear NMR (1H, 11B), and X-ray photoelectron spectroscopic characterization.

We use crystallographic data for four helical iron proteins (cytochrome c-b(562), cytochrome c’, sperm whale myoglobin, human cytoglobin) to calculate radial and angular signatures as each unfolds from the native state stepwise though four unfolded states. From these data we construct an angle phase diagram to display the evolution of each protein from its native state; and, in turn, the phase diagram is used to construct a funneled angle landscape for comparison with the topography of its folding energy landscape. We quantify the departure of individual helical and turning regions from the areal, angular profile of corresponding regions of the native state. This procedure allows us to identify the similarities and differences among individual helical and turning regions in the early stages of unfolding of the four helical heme proteins.

Separate focus on the oligomerization and oxidative cyclization steps required for the synthesis of 5,10,15-tris(trifluoromethyl)corrole revealed [bis(trifluoroacetoxy)iodo] benzene (PIFA) as a superior alternative oxidant. Under optimized conditions, the pure free-base corrole was obtained with a sixfold increase in chemical yield and an eleven-fold rise in isolated material per synthesis. The corresponding gallium(III) and manganese(III) complexes were isolated by adding the appropriate metal salt prior to corrole purification.

Time-resolved phosphorescence spectra of Re(CO)₃(dmp)⁺ and Re(CO)₃ (phen)⁺ chromophores (dmp = 4,7-dimethyl-1,10-phenanthroline, phen = 1,10-phenanthroline) bound to surface histidines (H83, H124, and H126) of Pseudomonas aeruginosa azurin mutants exhibit dynamic band maxima shifts to lower wavenumbers following 3-exponential kinetics with 1–5 and 20–100 ns major phases and a 1.1–2.5 μs minor (5–16%) phase. Observation of slow relaxation components was made possible by using an organometallic Re chromophore as a probe whose long phosphorescence lifetime extends the observation window up to ∼3 μs. Integrated emission-band areas also decay with 2- or 3-exponential kinetics; the faster decay phase(s) is relaxation-related, whereas the slowest one [360–680 ns (dmp); 90–140 ns (phen)] arises mainly from population decay. As a result of shifting bands, the emission intensity decay kinetics depend on the detection wavelength. Detailed kinetics analyses and comparisons with band-shift dynamics are needed to disentangle relaxation and population decay kinetics if they occur on comparable timescales. The dynamic phosphorescence Stokes shift in Re-azurins is caused by relaxation motions of the solvent, the protein, and solvated amino acid side chains at the Re binding site in response to chromophore electronic excitation. Comparing relaxation and decay kinetics of Re(dmp)124K122Cu^(II) and Re(dmp)124W122Cu^(II) suggests that electron transfer (ET) and relaxation motions in the W122 mutant are coupled. It follows that nanosecond and faster photo-induced ET steps in azurins (and likely other redox proteins) occur from unrelaxed systems; importantly, these reactions can be driven (or hindered) by structural and solvational dynamics.

Time-resolved phosphorescence spectra of Re(CO)