Synthesis, Spectroscopic and Nonlinear Optical Properties, and Antimicrobial Activity of Cu(II), Co(II), and Ni(II) Complexes: Experimental and Theoretical Studies.

Currently, we report the preparation of transition metal complexes Co(II), Ni(II), and Cu(II) of hydrazone Schiff base ligands, which are obtained by the condensation reaction of substituted salicylaldehyde and hydrazines. The synthesized hydrazone ligands and their metal complexes were characterized by spectroscopic methods such as Fourier transform infrared (FT-IR), UV-vis, nuclear magnetic resonance (1H NMR and C13 NMR), and mass spectrometry analyses. All of the quantum chemistry calculations were performed using DFT executed in the Gaussian 09 software package. The geometry was optimized by using the density functional theory (DFT) approximation at the B3LYP level with a basis set of 6-31G (d, p). There was excellent agreement between the FT-IR values obtained experimentally and those obtained theoretically for the test compounds. It is worth noting that none of the optimized geometries for any of the Schiff base and metal complexes had any eigenvalues that were negative, indicating that these geometries represent the true minimum feasible energy surfaces. We also analyzed the electrostatic potential of the molecule and NBO calculation at the same level of theory. Gauss View 6 was utilized for the file organization of the input data. Gauss View 6.0, Avogadro, and Chemcraft were used to determine the data. Additionally, synthesized compounds were screened for antimicrobial activity against Gram-negative bacteria (Salmonella typhi, Escherichia coli) and Gram-positive bacteria (Bacillus halodurans, Micrococcus luteus) and two fungal strains (Aspergillus flavus, Aspergillus niger). These research findings have established the potential of ligands and their metal complexes as antimicrobial agents. Additionally, the compounds demonstrated promising nonlinear optical (NLO) properties, with potential applications across a wide range of contemporary technologies.

Regulatory Considerations Toward Orphan Drug Designation and Orphan Drug Exclusivity in the United States and European Union: Structural Similarity, Clinical Superiority/Significant Benefit, and Case Studies.

The U.S. Food and Drug Administration and European Commission have developed successful orphan drug legislation to promote the research, development, and marketing approval of drugs to treat rare diseases. Central to these regulations are the concepts of structural similarity and clinical superiority/significant benefit to achieve orphan drug exclusivity. However, differences in health authority expectations remain regarding the qualification for an orphan drug designation, defining structural similarity, and demonstrating clinical superiority/significant benefit. These differences can create sponsor company uncertainty regarding the approvability of products (e.g., blocking risk by an existing orphan product) and divergent orphan drug decisions among health authorities. A comprehensive assessment of current regulations, case studies in exclusivities, and recommendations for improvement are presented.