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Vitamin B12derivatives (Cbls = cobalamins) exhibit photolytic properties upon excitation with light. These properties can be modulated by several factors including the nature of the axial ligands. Upon excitation, homolytic cleavage of the organometallic bond to the upper axial ligand takes place in photolabile Cbls. The photosensitive nature of Cbls has made them potential candidates for light-activated drug delivery. The addition of a fluorophore to the nucleotide loop of thiolato Cbls has been shown to shift the region of photohomolysis to within the optical window of tissue (600–900 nm). With this possibility, there is a need to analyze photolytic properties of unique Cbls which contain a Co–S bond. Herein, the photodissociation of one such Cbl, namely, N-acetylcysteinylcobalamin (NACCbl), is analyzed based on density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. The S0and S1potential energy surfaces (PESs), as a function of axial bond lengths, were computed to determine the mechanism of photodissociation. Like other Cbls, the S1PES contains metal-to-ligand charge transfer (MLCT) and ligand field (LF) regions, but there are some unique differences. Interestingly, the S1PES of NACCbl contains three distinct minima regions opening several possibilities for the mechanism of radical pair (RP) formation. The mild photoresponsiveness, observed experimentally, can be attributed to the small gap in energy between the S1and S0PESs. Compared to other Cbls, the gap shown for NACCbl is neither exactly in line with the alkyl Cbls nor the nonalkyl Cbls.

A diphenylalanine motif in peptides plays a crucial role in supramolecular systems. The current work represents a novel strategy in which a diphenylalanine motif in the central domain of neuropeptides conserves the specific Zn2+binding site and prevents “hopping” of the Zn2+ion between alternative metal binding sites. Alternative metal binding sites may also include carboxylic atoms in the terminal domains of a peptide. Therefore, one needs to design a peptide in which the metal will not bind the carboxylic groups in the terminal domains. Herein, we propose that engineering and designing peptides with a diphenylalanine motif in the central domain may yield excellent metal chelators.

The reaction of the ruthenium(II) complex fac-[Ru(CO)3Cl2(N1-thz)] (Ihereafter; thz = 1,3-thiazole) with human β-amyloid peptide 1-28 (Aβ28) and the resulting {Ru(CO)3}2+peptide adduct was investigated by a variety of biophysical methods. 1H NMR titrations highlighted a selective interaction of {Ru(CO)3}2+with Aβ28histidine residues; circular dichroism revealed the occurrence of a substantial conformational rearrangement of Aβ28; electrospray ionization mass spectrometry (ESI-MS) suggested a prevalent 1:1 metal/peptide stoichiometry and disclosed the nature of peptide-bound metallic fragments. Notably, very similar ESI-MS results were obtained when Iwas reacted with Aβ42. The implications of the above findings for a possible use of ruthenium compounds in Alzheimer’s disease are discussed.

Antivitamins B12represent an important class of vitamin B12analogues that have gained recent interest in several research areas. In particular, 4-ethylphenylcobalamin (EtPhCbl) and phenylethynylcobalamin (PhEtyCbl) exemplify two such antivitamins B12which have been characterized structurally and chemically. From a spectroscopic point of view, EtPhCbl is photolabile with a very low quantum yield of photoproducts, while PhEtyCbl is incredibly photostable. Herein, DFT and TD-DFT computations are provided to explore the photolytic properties of these compounds to shed light on the electronic properties that are indicative of these differences. Potential energy surfaces (PESs) were constructed to investigate the mechanisms of photodissociation leading to radical pair (RP) formation and the mechanisms of deactivation to the ground state. The S1PESs for each antimetabolite contain two energy minima, one being the metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation that can be identified for EtPhCbl but only one (path B) is energetically feasible and involves the lengthening of the Co–NImbond through the MLCT region followed by the lengthening of the Co–C bond through the LF region. For PhEtyCbl, there is not an energetically favorable path for photolysis; rather, internal conversion (IC) is the significantly preferred photophysical event.

The interactions between two peptide ligands [Ac763CCAASTTGDCH773(P1) and Ac743RRARSRVDIELLATRKSVSSCCAASTTGDCH773(P2)] derived from the cytoplasmic C-terminal region of Eschericha coliFeoB protein and Fe(II), Mn(II), and Zn(II) ions were investigated. The Feo system is regarded as the most important bacterial Fe(II) acquisition system, being one of the key virulence factors, especially in anaerobic conditions. Located in the inner membrane of Gram-negative bacteria, FeoB protein transports Fe(II) from the periplasm to the cytoplasm. Despite its crucial role in bacterial pathogenicity, the mechanism in which the metal ion is trafficked through the membrane is not yet elucidated. In the gammaproteobacteria class, the cytoplasmic C-terminal part of FeoB contains conserved cysteine, histidine, and glutamic and aspartic acid residues, which could play a vital role in Fe(II) binding in the cytoplasm, receiving the metal ion from the transmembrane helices. In this work, we characterized the complexes formed between the whole cytosolic C-terminal sequence of E. coliFeoB (P2) and its key polycysteine region (P1) with Fe(II), Mn(II), and Zn(II) ions, exploring the specificity of the C-terminal region of FeoB. With the help of a variety of potentiometric, spectroscopic (electron paramagnetic resonance and NMR), and spectrometric (electrospray ionization mass spectrometry) techniques and molecular dynamics, we propose the metal-binding modes of the ligands, compare their affinities toward the metal ions, and discuss the possible physiological role of the C-terminal region of E. coliFeoB.