Epilogue to the Gerald Maggiora Festschrift: a tribute to an exemplary mentor,colleague, collaborator,and innovator

Journal of Computer-Aided Molecular Design - In May 2022, JCAMD published a Special Issue in honor of Gerald (Gerry) Maggiora, whose scientific leadership over many decades advanced the fields of...     

Vector algebra and molecular symmetry: a tribute to Professor Josiah Willard Gibbs

Vector algebra, as developed by Josiah Willard Gibbs, is much simpler than matrix or tensor algebra, therefore, it is more suitable to introduce the students of chemistry into the wonderful world of molecular symmetry. A program based on elementary vector algebra has been written to determine all symmetry elements and symmetry operations of rigid molecular structures. The program also contains data for 57 point groups common in chemistry. Therefore, it automatically supplies the particular point group to which the structure belongs. Since the locations of the nuclei related to the symmetry elements are also revealed by the program, even the detailed notation of the framework group of the molecular structure can be deduced. The program can be a great help in determining the symmetries of the normal modes of vibration, too.     

Phloretin,as a Potent Anticancer Compound: From Chemistry to Cellular Interactions

Phloretin is a natural dihydrochalcone found in many fruits and vegetables, especially in apple tree leaves and the Manchurian apricots, exhibiting several therapeutic properties, such as antioxidant, antidiabetic, anti-inflammatory, and antitumor activities. In this review article, the diverse aspects of the anticancer potential of phloretin are addressed, presenting its antiproliferative, proapoptotic, antimetastatic, and antiangiogenic activities in many different preclinical cancer models. The fact that phloretin is a planar lipophilic polyphenol and, thus, a membrane-disrupting Pan-Assay Interference compound (PAIN) compromises the validity of the cell-based anticancer activities. Phloretin significantly reduces membrane dipole potential and, therefore, is expected to be able to activate a number of cellular signaling pathways in a non-specific way. In this way, the effects of this minor flavonoid on Bax and Bcl-2 proteins, caspases and MMPs, cytokines, and inflammatory enzymes are all analyzed in the current review. Moreover, besides the anticancer activities exerted by phloretin alone, its co-effects with conventional anticancer drugs are also under discussion. Therefore, this review presents a thorough overview of the preclinical anticancer potential of phloretin, allowing one to take the next steps in the development of novel drug candidates and move on to clinical trials.     

Guest Editorial: A path through quantum crystallography: a short tribute to Professor Lou Massa

Professor Lou Massa’s contributions since the late 1960s to the founding of the field now known as “Quantum Crystallography” (QCr) are briefly described. The term itself has been coined in 1995 by L. Huang, L. Massa, and J. Karle (1985 Nobel Laureate in Chemistry). Originally, QCr referred to the Clinton-Massa’s iterative approach that, for the first time, delivered N-representable electron densities that are consistent with the observed structure factors. These densities satisfy, at once, experimental observation and the necessarily underlying quantum mechanical requirement of being derived from an antisymmetric wavefunction. The single-determinantal quantum mechanical structure Huang, Massa, and Karle (HMK) imposed in their original work can be extended to any method that uses MOs including CI or DFT, as they demonstrate in their papers. HMK use the Clinton-Massa method to reconstruct approximations to the first order reduced density matrix of large molecules in a piecemeal manner from computationally-tractable fragments. The idea was also adapted by J. Hernández Trujillo and R. F. W. Bader in the context of the Quantum Theory of Atoms in Molecules (QTAIM). Massa et al. simplified and generalized this fragmentation method into what came to be known as the “Kernel Energy Method” (KEM) which delivers the properties of large molecules accurately, at a fraction of the computational time, and within any model chemistry as applications to DNA, tRNA, the proto-ribosome, insulin, and graphene, amply demonstrate. Lou Massa has also pushed the envelope in other directions as well. In 1992, he and W. Lipscomb (1976 Nobel Laureate in Chemistry) published several papers predicting the structure and stability of Boron nanotubes and boron fullurene 12 years before they were eventually synthesized in laboratories at Yale and at Brookhaven. More recently, in 2006 L. Massa, J. Karle, and A. Yonath (2009 Nobel Laureate in Chemistry) (MKY) proposed a startling alternative to the then widely-accepted mechanism of the peptide bond formation in the active site of the ribosome. In sharp contrast with the accepted “shuttle mechanism”, MKY’s “direct” mechanism is simpler and, importantly, reproduces the measured thermodynamic and kinetic parameters. Massa has also contributed to other domains, for example interstellar chemistry, and to the policy, history, and philosophy of science. His TV program and Oxford University Press book (both titled “Science and the Written Word”) represent an invaluable and candid documentation of some of the key discoveries in the words of a dozen Nobel Laureates and a constellation of scholars representing the Who’s Who of current science. It is with both admiration and affection that this paper (and this issue) is dedicated to Lou Massa, the person and the scientist.