The extracellular calcium-sensing receptor (CaSR) controls vital bone cell functions such as cell growth, differentiation and apoptosis. The binding of the native agonist (Ca²⁺) to CaSR activates the receptor, which undergoes structural changes that trigger a cascade of events along the cellular signaling pathways. Strontium (in the form of soluble salts) has been found to also be a CaSR agonist. The activation of the receptor by Sr²⁺ is considered to be the major mechanism through which strontium exerts its anti-osteoporosis effect, mostly in postmenopausal women. Strontium-activated CaSR initiates a series of signal transduction events resulting in both osteoclast apoptosis and osteoblast differentiation, thus strengthening the bone tissue. The intimate mechanism of Sr²⁺ activation of CaSR is still enigmatic. Herewith, by employing a combination of density functional theory (DFT) calculations and polarizable continuum model (PCM) computations, we have found that the Ca²⁺ binding sites 1, 3, and 4 in the activated CaSR, although possessing a different number and type of protein ligands, overall structure and charge state, are all selective for Ca²⁺ over Sr²⁺. The three binding sites, regardless of their structural differences, exhibit almost equal metal selectivity if they are flexible and have no geometrical constraints on the incoming Sr²⁺. In contrast to Ca²⁺ and Sr²⁺, Mg²⁺ constructs, when allowed to fully relax during the optimization process, adopt their stringent six-coordinated octahedral structure at the expense of detaching a one-backbone carbonyl ligand and shifting it to the second coordination layer of the metal. The binding of Mg²⁺ and Sr²⁺ to a rigid/inflexible calcium-designed binding pocket requires an additional energy penalty for the binding ion; however, the price for doing so (to be paid by Sr²⁺) is much less than that of Mg²⁺. The results obtained delineate the key factors controlling the competition between metal cations for the receptor and shed light on some aspects of strontium’s therapeutic effects.

Absorption and fluorescence spectra in acetonitrile for a series of substituted aryl hydrazones of N-hexyl-1,8-naphthalimide are studied with the aim of potential application of the compounds for enzyme activity localization. The influence of the substituents on the spectral characteristics has been evaluated. The absorption and fluorescence energies of substituted aryl-1,8-naphthalimide hydrazones have been calculated with the PCM TDDFT formalism. The M06 and PBE0 functionals, combined with the 6-31+G(d) atomic basis set, have been found to accurately model the excited state properties of the present set of solvated fluorophores. Absorption and fluorescence spectral characteristics have been rationalized in terms of experimental and theoretical electronic indices in order to assess their predictive abilities for application in designing analogues with good emitting properties. An excellent linear dependence is established between the experimental fluorescence and Hammett σ⁺ _p substituent constants and on the other hand σ⁺ _p constants correlate with the theoretically calculated values for the electrostatic potential at nuclei (EPN). A model for predicting the fluorescence properties of substituted hydrazones by means of EPN is drawn, including the polysubstituted derivatives, where Hammett constants are not applicable.

Recent advances in quantifying nucleophilic reactivities in chemical reactions and intermolecular interactions of aromatic molecules are reviewed. This survey covers experimental (IR frequency shifts induced by hydrogen bonding) and theoretical (modeling of potential energy surfaces, atomic charges, molecular electrostatic potential) approaches in characterizing chemical reactivity. Recent advances in software developments assisting the evaluation of the reactive sites for electrophilic aromatic substitution are briefly discussed.

The secondary structure of proteins is of prime importance to their proper functioning and protein misfolding may cause serious disorders in the human body. Here, the electric field influence on the conformational stability of model alpha helical peptides is studied by employing density functional theory calculations combined with continuum dielectric method computations. Our results show that the basic parameters of the electric field – its strength and directionality – are determinative for the alpha helix stability. An electric field strength of 0.005 a.u. (2.5 V nm⁻¹) applied along the X coordinate axis (the long axis of the helix) in the direction of the μ_x component of the molecular dipole moment does affect the peptide conformation, destroys the helix, and leads to the formation of a cyclic-peptide-like structure. Interestingly, the process of denaturation can be reversible when the electric field is switched-off. The reversibility of the process of the electric field induced disruption of the peptide secondary structure suggests a possible mechanism for the healing of misfolded proteins.

Three new 1,8-naphthalimide derivatives M1–M3 with different substituents at the C-4 position have been synthesized and characterized. Their photophysical properties have been investigated in organic solvents of different polarity, and their fluorescence intensity was found to depend strongly on both the polarity of the solvents and the type of substituent at C-4. For compounds M1 and M2 having a tertiary amino group linked via an ethylene bridge to the chromophore system, high quantum yield was observed only in non-polar media, whereas for compound M3, the quantum efficiency did not depend on the medium polarity. The effect of different metal ions (Ag⁺, Ba²⁺, Cu²⁺, Co²⁺, Mg²⁺, Pb²⁺, Sr²⁺, Fe³⁺, and Sn²⁺) on the fluorescence emission of compounds M1 and M2 was investigated. A significant enhancement has been observed in the presence of Ag⁺, Pb²⁺, Sn²⁺, Co²⁺, Fe³⁺, as this effect is expressed more preferably in the case of M2. Both compounds have shown significant pH dependence, as the fluorescence intensity was low in alkaline medium and has been enhanced more than 20-fold in acidic medium. The metal ions and pH do not affect the fluorescence intensity of M3. Density-functional theory (DFT) and Time-dependent density-functional theory (TDDFT) quantum chemical calculations are employed in deciphering the intimate mechanism of sensor mechanism. The functional properties of M1 and M2 were compared with polyamidoamine (PAMAM) dendrimers of different generations modified with 1,8-naphthalimide.

The rational design of cyanine dyes for the fine-tuning of their photophysical properties undoubtedly requires theoretical considerations for understanding and predicting their absorption and fluorescence characteristics. The present study aims to assess the applicability and accuracy of several DFT functionals for calculating the absorption and fluorescence maxima of monomethine cyanine dyes. Ten DFT functionals and different basis sets were examined to select the proper theoretical model for calculating the electronic transitions of eight representative molecules from this class of compounds. The self-aggregation of the dyes was also considered. The pure exchange functionals (M06L, HFS, HFB, B97D) combined with the triple-zeta basis set 6-311+G(2d,p) showed the best performance during the theoretical estimation of the absorption and fluorescent characteristics of cyanine dyes.