Be2+ Causes Hypersensitivity but Mg2+ and Ca2+ Do Not─Favorable Metal Coordination Is the Key for Differential Allosteric Modulation and Binding Affinities.

Although the ion selectivity of metalloproteins has been well established, selective metal antigen recognition by immunoproteins remains elusive. One such case is the recognition of the Be2+ ion against its heavier congeners, Mg2+ and Ca2+, by the human leukocyte antigen immunoprotein (HLA-DP2), leading to immunotoxicity. Integrating with our previous mechanistic study on Be2+ toxicity, herein, we have explored the basis of characteristic nontoxicity of Mg2+ and Ca2+ ions despite their in vivo abundance. The ion binding cleft of the HLA-DP2-peptide complex is composed of four acidic residues, p4D and p7E from the peptide and ß26E and ß69E from the protein. While the tetrahedral coordination site of the smaller Be2+ ion is located deep inside the cavity, hexa- to octa-coordination sites of Mg2+ and Ca2+ ions are located closer to the protein surface. The intrinsic high coordination number of Mg2+/Ca2+ ions induces allosteric modifications on the HLA-DP2_M2 surface, which are atypical for TCR recognition. Furthermore, the lower binding energy of larger Mg2+ and Ca2+ ions with the cavity residues can be correlated to the lower charge density and reduced covalent bonding nature as compared to those of the smaller Be2+ ion. In short, weak binding of Mg2+ and Ca2+ ions and the unfavorable allosteric surface modifications are probably the major determinants for the absence of Mg2+/Ca2+ ion-mediated hypersensitivity in humans.

Site-selective post-modification of short α/γ hybrid foldamers: a powerful approach for molecular diversification towards biomedical applications.

The extensive research work in the exhilarating area of foldamers (artificial oligomers possessing well-defined conformation in solution) has shown them to be promising candidates in biomedical research and materials science. The post-modification approach is successful in peptides, proteins, and polymers to modulate their functions. To the best of our knowledge, site-selective post-modification of a foldamer affording molecules with different pendant functional groups within a molecular scaffold has not yet been reported. We demonstrate for the first time that late-stage site-selective functionalization of short hybrid oligomers is an efficient approach to afford molecules with diverse functional groups. In this article, we report the design and synthesis of hybrid peptides with repeating units of leucine (Leu) and 5-amino salicylic acid (ASA), regioselective post-modification, conformational analyses (based on solution-state NMR, circular dichroism and computational studies) and morphological studies of the peptide nanostructures. As a proof-of-concept, we demonstrate the applications of differently modified peptides as drug delivery agents, imaging probes, and anticancer agents. The novel feature of the work is that the difference in reactivity of two phenolic OH groups in short biomimetic peptides was utilized to achieve site-selective post-modification. It is challenging to apply the same approach to short α-peptides having a poor folding tendency, and their post-functionalization may considerably affect their conformation.

Hydrogen Evolution Activity of Nitrogen-Rich g-C3-xN4+x Synthesized by Solid-Gas Interface Method.

Synthesis of a metal-free carbon nitride (g-C3N4) photocatalyst in the form of nitrogen-rich g-C3-xN4+x derivatives is desirable for efficient solar to hydrogen conversion and remains a challenging task to achieve. Herein we report the development of homogeneous sheets of nitrogen-rich graphitic carbon nitride samples from melamine by a solid-gas interface approach. Using this method, pure g-C3N4 (CN), g-C3-xN4+x under ammonia flow (CN-NH3) and g-C3-xN4+x under nitrogen flow (CN-N2) are prepared. The g-C3-xN4+x (CN-NH3) sample shows better surface conductivity, wide optical absorbance in the visible region, reduced recombination and high electron donor density, and higher performance toward photoelectrochemical hydrogen evolution (HER). The g-C3-xN4+x (CN-NH3) generates a photocurrent of 2.06 µA cm-2, which is 2.5 times higher than that of the pure g-C3N4 (CN) sample (0.85 µA cm-2). It also shows higher photocatalytic water splitting ability compared to the CN and CN-N2 samples, generating 634 µmol g-1 hydrogen without cocatalyst and 1163 µmol g-1 of hydrogen with Pt cocatalyst. Density functional calculations suggest that the progressive band gap reduction with the increase in the N-dopant percentage can be attributed to the gradual increase in the partial π-occupations, which can lead to a significant stabilization of the conduction band minima. The theoretical modeling, however, indicates a saturation in the band gap effect after 75% of N-dopant. The onset potential of g-C3-xN4+x for HER appears at η = 0.43 V in dark and η = 0.34 V vs Ag/AgCl under solar light illumination of 1 sun.

Molecular mechanism of Be2+-ion binding to HLA-DP2: tetrahedral coordination, conformational changes and multi-ion binding.

The chemistry of beryllium is rather unusual, however, less explored as compared to other main group elements. This is mainly attributed to the high toxicity of beryllium, leading to chronic granulomatous pneumonitis, called chronic beryllium disease (CBD). It has been reported that Be2+-ion binding to the human leukocyte antigen protein (HLA-DP2) and peptide (M2) results in favorable interaction with the T-cell receptor protein (TCR), which initiates immune-mediated toxicity. We have carried out molecular dynamics (MD) simulations combined with quantum mechanical/molecular mechanical (QM/MM) studies to explore the binding nature of Be2+ with a HLA-DP2 protein and M2 peptide. The interaction between the negatively charged M2 peptide and the negatively charged binding cleft of HLA-DP2 is unfavorable. However, this interaction is stabilized by one Be2+ and two Na+-ions bridged by negatively charged carboxyl groups of glutamate residues (ß26E and ß69E) of the ß-chain of HLA-DP2 and one glutamate (p7E) and one aspartate residue (p4D) of the M2 peptide. This multi-ion cavity consists of tetrahedrally coordinated static Be2+ and Na+-ions, as well as one dynamically exchangeable Na+-ion. The smaller size and higher charge of the Be2+-ion as compared to the Na+-ion reduce the distance between the M2 peptide and the ß-chain of HLA-DP2, which results in conformational change suitable for TCR binding. However, the replacement of the Be2+ by the Na+-ion could not generate a suitable binding site for TCR.

An Aluminum Dihydride Working as a Catalyst in Hydroboration and Dehydrocoupling.

The well-defined aluminum dihydride LAlH2 (L = HC(CMeNAr)2, Ar = 2,6-Et2C6H3) (1) operates in catalysis like a transition metal complex. The catalytic activity of 1 for hydroboration of terminal alkynes was investigated. Furthermore, catalyst 1 effectively initiated the dehydrocoupling of boranes with amines, thiols, and phenols, respectively, to form compounds with B-E bonds (E = N, S, O) under elimination of H2. Quantum mechanical calculations indicate that hydroboration and dehydrocoupling reactions occur via three consecutive cycloaddition reactions involving the activation of the X-H (X = Al, B, C, and O) σ-bonds.

An Aluminum Hydride That Functions like a Transition-Metal Catalyst.

The reaction of [LAlH2 ] (L=HC(CMeNAr)2 , Ar=2,6-iPr2 C6 H3 ) with MeOTf (Tf=SO2 CF3 ) resulted in the formation of [LAlH(OTf)] (1) in high yield. The triflate substituent in 1 increases the positive charge at the aluminum center, which implies that 1 has a strong Lewis acidic character. The excellent catalytic activity of 1 for the hydroboration of organic compounds with carbonyl groups was investigated. Furthermore, it was shown that 1 effectively initiates the addition reaction of trimethylsilyl cyanide (TMSCN) to both aldehydes and ketones. Quantum mechanical calculations were carried out to explore the reaction mechanism.

Neutral tricoordinated beryllium(0) compounds--isostructural to BH(3) but isoelectronic to NH(3).

The electronic structure and reactivity of neutral tricoordinated Be(0) compounds BeL(3), L = CO (1), NHC (2) and PMe(3) (3) are explored by quantum mechanical calculations. These BeL(3) complexes are found to be planar or nearly planar like electron deficient BH3 but isoelectronic with NH3 and possess three L→Be donor-acceptor bonds. The Be atom can be considered as sp(2)-hybridized with a lone pair in the highly diffused 2p(z)-orbital in contrast to the sp(3) hybridization in isoelectronic NH(3). Even though the lone pair on Be is stabilized through π-back donation or hyperconjugative interaction with the ligands, yet it is highly reactive towards Lewis acids such as H(+), BH(3) and W(CO)(5). The calculated gas phase protonation energies reveal that the NHC complex 2 and the trimethylphosphine complex 3 are 'super basic' in nature. Promising ligand property of BeL(3) has also been noted with BH(3) and transition metal fragment W(CO)(5). Besides, the reactivity of 2 and 3 is found to be more as compared to 1.

Borylene-based functionalization of iron-alkynyl-σ-complexes and stepwise reversible metal-boryl-to-borirene transformation: synthesis, characterization, and density functional theory studies.

Thermally induced chemoselective borylene transfer from [(OC)(5)Mo=BN(SiMe(3))(2)] (2a) to the carbon-carbon triple bond of an iron dicarbonyl alkynyl complex [(η(5)-C(5)Me(5))Fe(CO)(2)C≡CPh] (3) led to the isolation of an iron aminoborirene complex [(η(5)-C(5)Me(5))(OC)(2)Fe{µ-BN(SiMe(3))(2)C=C}Ph] (4) in satisfactory yield. Room temperature photolysis of 4 resulted in an unprecedented rearrangement and a concurrent decarbonylation, affording the novel C(2) side-on coordinated iron boryl complex [(η(5)-C(5)Me(5))(OC)FeBN(SiMe(3))(2)(η(2)-CC)Ph] (5). Carbonylation of 5 under CO atmosphere at ambient temperature yielded [(η(5)-C(5)Me(5))(OC)(2)FeBN(SiMe(3))(2)CCPh] (6), which is an isomer of 4. Decarbonylation of 6 at 80 °C led to 5, which could be upon introduction of CO gas further converted into 4 under same conditions. Reaction of 5 with PMe(3) at 80 °C yielded the phosphane complex [(η(5)-C(5)Me(5))(OC)(PMe(3))Fe{µ-BN(SiMe(3))(2)C=C}Ph] (7). All above-mentioned iron complexes 4-7 were isolated as air and moisture sensitive crystalline solids in good yields and have been fully characterized in solution and by X-ray crystallography. Quantum chemical calculations using density functional theory (DFT) have been carried out to understand the mechanisms of the experimentally observed reactions and to analyze the bonding situation in the molecules 4-7.