Heme Bound Amylin: Spectroscopic Characterization, Reactivity, and Relevance to Type 2 Diabetes

Deposition of human amylin or islet amyloid polypeptide (hIAPP) within the β-cells of the pancreatic islet of Langerhans is implicated in the etiology of type 2 diabetes mellitus (T2Dm). Accumulating evidences suggest that increased body iron stores, iron overload, and, in particular, higher heme-iron intake is significantly associated with higher risk of Type 2 diabetes mellitus (T2Dm) (<i>PloS One</i> <b>2012</b>, <i>7</i>, e41641). Some key pathological features of T2Dm, like iron dyshomeostasis, iron accumulation, mitochondrial dysfunction, and oxidative stress are very similar to the cytopathologies of Alzheimer’s disease, which have been invoked to be due to heme complexation with amyloid β peptides. The similar etiology and pathogenic features in both Alzheimer’s disease (AD) and T2Dm indicate a common underlying mechanism, with heme playing an important role. In this study we show that hIAPP can bind heme. His18 residue of hIAPP binds heme under physiological conditions and results in an axial high-spin active site with a trans-axial water derived ligand. Arg11 is a key residue that is also essential for heme binding. Heme­(Fe²⁺)-hIAPP complexes are prone to produce partially reduced oxygen species (PROS). The His18 residue identified in this study is absent in rats which do not show T2Dm, implicating the significance of this residue as well as heme in the pathology of T2Dm

Apomyoglobin Sequesters Heme from Heme Bound Aβ Peptides

A combination of absorption, electron paramagnetic resonance (EPR), and resonance Raman (rR) spectroscopy has been used to study the interaction of heme-Aβ and apomyoglobin (apoMb). The absorption spectrum of oxidized heme bound Aβ, characterized by a split Soret band at 364 and 394 nm, shifts to 408 nm on incubation with apoMb, characteristic of Myoglobin (Mb). The ν₄, ν₃, and ν₂ bands in the rR spectrum of heme-Aβ are observed at 1376, 1495, and 1570 cm^–1, which shift to 1371, 1482, and 1563 cm^–1, respectively on incubating with apoMb, implying formation of Mb. Similarly, heme transfer from reduced heme-Aβ to apoMb resulting in the formation of deoxyMb was also observed. Thus, spectroscopic data show that apoMb can sequester heme from heme-Aβ complexes both in oxidized and in reduced forms. Heme uptake by apoMb from native heme-Aβ(1–40) and Aβ(1–16) in both oxidized and reduced forms follow a biphasic reaction kinetics likely representing heme transfer from two dominating conformers of heme-Aβ in solution. The rate constants for the two steps involved in heme uptake by apoMb from heme-Aβ(1–40) are 11.5 × 10⁴ M^–1 s^–1 and 7.5 × 10³ M^–1 s^–1 while from heme-Aβ(1–16) are 6.0 × 10⁴ M^–1 s^–1 and 7.5 × 10³ M^–1 s^–1. The rate constants for heme uptake by apoMb from reduced heme-Aβ(1–40) are 3.7 × 10⁴ M^–1 s^–1 and 6.8 × 10³ M^–1 s^–1 while for reduced heme-Aβ(1–16) are 2.0 × 10⁴ M^–1 s^–1 and 6.0 × 10³ M^–1 s^–1. The heme uptake from heme-Aβ by apoMb leads to a dramatic reduction of PROS generation by the reduced heme-Aβ complexes

Spiers Memorial Lecture: Coordination networks that switch between nonporous and porous structures: an emerging class of soft porous crystals

Coordination networks (CNs) are a class of (usually) crystalline solids typically comprised of metal ions or cluster nodes linked into 2 or 3 dimensions by organic and/or inorganic linker ligands. Whereas CNs tend to exhibit rigid structures and permanent porosity as exemplified by most metal–organic frameworks, MOFs, there exists a small but growing class of CNs that can undergo extreme, reversible structural transformation(s) when exposed to gases, vapours or liquids. These “soft” or “stimuli-responsive” CNs were introduced two decades ago and are attracting increasing attention thanks to two features: the amenability of CNs to design from first principles, thereby enabling crystal engineering of families of related CNs; and the potential utility of soft CNs for adsorptive storage and separation. A small but growing subset of soft CNs exhibit reversible phase transformations between nonporous (closed) and porous (open) structures. These “switching CNs” are distinguished by stepped sorption isotherms coincident with phase transformation and, perhaps counterintuitively, they can exhibit benchmark properties with respect to working capacity (storage) and selectivity (separation). This review addresses fundamental and applied aspects of switching CNs through surveying their sorption properties, analysing the structural transformations that enable switching, discussing structure–function relationships and presenting design principles for crystal engineering of the next generation of switching CNs

Coupled 3D (<i>J</i> ≥ 0) Time-Dependent Wave Packet Calculation for the F + H₂ Reaction on Accurate Ab Initio Multi-State Diabatic Potential Energy Surfaces

We had calculated adiabatic potential energy surfaces (PESs), nonadiabatic, and spin–orbit (SO) coupling terms among the lowest three electronic states (12A′, 22A′, and 12A″) of the F + H2 system using the multireference configuration interaction (MRCI) level of theory, and the adiabatic-to-diabatic transformation equations were solved to formulate the diabatic Hamiltonian matrix [J. Chem. Phys. 2020, 153, 174301] for the entire region of the nuclear configuration space. The accuracy of such diabatic PESs is explored by performing scattering calculations to evaluate integral cross sections (ICSs) and rate constants. The nonadiabatic and SO effects are studied by utilizing coupled 3D time-dependent wave packet formalism with zero and nonzero total angular momentum on multiple adiabatic/diabatic surfaces calculation. We depict the convergence profiles of reaction probabilities for the reactive as well as nonreactive processes on various electronic states at different collision energies with respect to total angular momentum including all helicity quantum numbers. Finally, total ICSs are calculated as functions of collision energies for the initial rovibrational state (v = 0, j = 0) of the H2 molecule along with the temperature-dependent rate coefficient, where those quantities are compared with previous theoretical and experimental results

Peroxidase to Cytochrome <i>b</i> Type Transition in the Active Site of Heme-Bound Amyloid β Peptides Relevant to Alzheimer’s Disease

Recent evidence has established the colocalization of amyloid-rich plaques and heme-rich deposits in the human cerebral cortex as a common postmortem feature in Alzheimer’s disease (AD). The amyloid β (Aβ) peptides have been shown to bind heme, and the resultant heme–Aβ complexes can generate toxic partially reduced oxygen species (PROS) and exhibit peroxidase activity. The heme–Aβ active site exhibits a concentration-dependent equilibrium between a high-spin mono-His-bound species similar to a peroxidase-type active site and a bis-His-bound six-coordinate low-spin species similar to that of a cytochrome <i>b</i> type active site. The ν_Fe–His (241 cm^–1) vibration has been identified in the high-spin heme–Aβ active site by resonance Raman spectroscopy. The formation of the low-spin heme–Aβ species is promoted by the His14 and noncoordinating second-sphere Arg5 residues. The high-spin state produces more PROS than the low-spin species. Nonbiological constructs modeling different forms of Aβ (oligomers, fibrils, etc.) suggest that the detrimental high-spin state is likely to dominate under most physiological conditions

Crystal engineering of porous coordination networks to enable separation of C2 hydrocarbons

Crystal engineering, the field of chemistry that studies the design, properties, and applications of crystals, is exemplified by the emergence over the past thirty years of porous coordination networks (PCNs), including metal-organic frameworks (MOFs) and hybrid coordination networks (HCNs). PCNs have now come of age thanks to their amenability to design from first principles and how this in turn can result in new materials with task-specific features. Herein, we focus upon how control over the pore chemistry and pore size of PCNs has been leveraged to create a new generation of physisorbents for efficient purification of light hydrocarbons (LHs). The impetus for this research comes from the need to address LH purification processes based upon cryogenic separation, distillation, chemisorption or solvent extraction, each of which is energy intensive. Adsorptive separation by physisorbents (in general) and PCNs (in particular) can offer two advantages over these existing approaches: improved energy efficiency; lower plant size/cost. Unfortunately, most existing physisorbents suffer from low uptake and/or poor sorbate selectivity and are therefore unsuitable for trace separations of LHs including the high volume C2 LHs (C2Hx, x = 2, 4, 6). This situation is rapidly changing thanks to PCN sorbents that have set new performance benchmarks for several C2 separations. Herein, we review and analyse PCN sorbents with respect to the supramolecular chemistry of sorbent-sorbate binding and detail the crystal engineering approaches that have enabled the exquisite control over pore size and pore chemistry that affords highly selective binding sites. Whereas the structure-function relationships that have emerged offer important design principles, several development roadblocks remain to be overcom

Beyond Born–Oppenheimer theory for spectroscopic and scattering processes

We review our development on beyond Born–Oppenheimer (BBO) theory and its implementation on various models and realistic molecular processes as carried out over the last 15 years. The theoretical formulation leading to the BBO equations are thoroughly discussed with ab initio calculations. We have employed first principle based BBO theory not only to formulate single surface extended Born–Oppenheimer equation to understand the nature of nonadiabatic effect but also to construct accurate diabatic potential energy surfaces (PESs) for important spectroscopic systems, namely, NO2 radical, Na3 and K3 clusters, NO3 radical, benzene and 1,3,5-trifluorobenzene radical cations (C6H6+ and C6H3F3+) as well as triatomic reactive scattering systems like H++H2 and F+H2. The nonadiabatic phenomena like Jahn–Teller (JT), Renner–Teller, pseudo Jahn–Teller effects and the accidental conical intersections are the key players in dictating spectroscopic and reactive scattering profiles. The nature of diabatic coupling elements derived from ab initio data with BBO theory for molecular processes in Franck-Condon region has been analysed in the context of linearly and bilinearly coupled JT model Hamiltonian. The results obtained from quantum dynamical calculations on BBO based diabatic PESs of the above molecular systems are found to be in accord with available experimental outcomes.</p

ADT: A Generalized Algorithm and Program for Beyond Born–Oppenheimer Equations of “<i>N</i>” Dimensional Sub-Hilbert Space

The major bottleneck of first principle based beyond Born–Oppenheimer (BBO) treatment originates from large number and complicated expressions of adiabatic to diabatic transformation (ADT) equations for higher dimensional sub-Hilbert spaces. In order to overcome such shortcoming, we develop a generalized algorithm, “ADT” to generate the nonadiabatic equations through symbolic manipulation and to construct highly accurate diabatic surfaces for molecular processes involving excited electronic states. It is noteworthy to mention that the nonadiabatic coupling terms (NACTs) often become singular (removable) at degenerate point(s) or along a seam in the nuclear configuration space (CS) and thereby, a unitary transformation is required to convert the kinetically coupled (adiabatic) Hamiltonian to a potentially (diabatic) one to avoid such singularity­(ies). The “ADT” program can be efficiently used to (a) formulate analytic functional forms of differential equations for ADT angles and diabatic potential energy matrix and (b) solve the set of coupled differential equations numerically to evaluate ADT angles, residue due to singularity­(ies), ADT matrices, and finally, diabatic potential energy surfaces (PESs). For the numerical case, user can directly provide ab initio data (adiabatic PESs and NACTs) as input files to this software or can generate those input files through in-built python codes interfacing MOLPRO followed by ADT calculation. In order to establish the workability of our program package, we selectively choose six realistic molecular species, namely, NO2 radical, H3+, F + H2, NO3 radical, C6H6+ radical cation, and 1,3,5-C6H3F3+ radical cation, where two, three, five and six electronic states exhibit profound nonadiabatic interactions and are employed to compute diabatic PESs by using ab initio calculated adiabatic PESs and NACTs. The “ADT” package released under the GNU General Public License v3.0 (GPLv3) is available at https://github.com/AdhikariLAB/ADT-Program and also as the Supporting Information of this article

ADT: A Generalized Algorithm and Program for Beyond Born–Oppenheimer Equations of “<i>N</i>” Dimensional Sub-Hilbert Space

The major bottleneck of first principle based beyond Born–Oppenheimer (BBO) treatment originates from large number and complicated expressions of adiabatic to diabatic transformation (ADT) equations for higher dimensional sub-Hilbert spaces. In order to overcome such shortcoming, we develop a generalized algorithm, “ADT” to generate the nonadiabatic equations through symbolic manipulation and to construct highly accurate diabatic surfaces for molecular processes involving excited electronic states. It is noteworthy to mention that the nonadiabatic coupling terms (NACTs) often become singular (removable) at degenerate point(s) or along a seam in the nuclear configuration space (CS) and thereby, a unitary transformation is required to convert the kinetically coupled (adiabatic) Hamiltonian to a potentially (diabatic) one to avoid such singularity­(ies). The “ADT” program can be efficiently used to (a) formulate analytic functional forms of differential equations for ADT angles and diabatic potential energy matrix and (b) solve the set of coupled differential equations numerically to evaluate ADT angles, residue due to singularity­(ies), ADT matrices, and finally, diabatic potential energy surfaces (PESs). For the numerical case, user can directly provide ab initio data (adiabatic PESs and NACTs) as input files to this software or can generate those input files through in-built python codes interfacing MOLPRO followed by ADT calculation. In order to establish the workability of our program package, we selectively choose six realistic molecular species, namely, NO2 radical, H3+, F + H2, NO3 radical, C6H6+ radical cation, and 1,3,5-C6H3F3+ radical cation, where two, three, five and six electronic states exhibit profound nonadiabatic interactions and are employed to compute diabatic PESs by using ab initio calculated adiabatic PESs and NACTs. The “ADT” package released under the GNU General Public License v3.0 (GPLv3) is available at https://github.com/AdhikariLAB/ADT-Program and also as the Supporting Information of this article

Jahn–Teller Effect in Orthorhombic Manganites: <i>Ab Initio</i> Hamiltonian and Roto-vibrational Spectrum

For the first time, using three different electronic structure methodologies, namely, CASSCF, RS2c, and MRCI­(SD), we construct ab initio adiabatic potential energy surfaces (APESs) and nonadiabatic coupling term (NACT) of two electronic states (5Eg) of MnO69– unit, where eight such units share one La atom in LaMnO3 crystal. While fitting those APESs with analytic functions of normal modes (Qx, Qy), an empirical scaling factor is introduced considering the mass ratio of eight MnO69– units with and without one La atom to explore the environmental (mass) effect on MnO69– unit. When the roto-vibrational levels of MnO69– Hamiltonian are calculated, peak positions computed from ab initio constructed excited APESs are found to be enough close with the experimental satellite transitions [J. Exp. Theor. Phys. 2016, 122, 890−901] endorsing our earlier model results [J. Chem. Phys. 2019, 150, 064703]. In order to explore the electron–nuclear coupling in an alternate way, theoretically “exact” and numerically “accurate” beyond Born–Oppenheimer (BBO) theory based diabatic potential energy surfaces (PESs) of MnO69– are constructed to generate the photoelectron (PE) spectra. The PE spectral band also exhibits good peak by peak correspondence with the higher satellite transitions in the dielectric function spectra of the LaMnO3 complex