Can Spin-Component Scaled MP2 Achieve kJ/mol Accuracy for Cohesive Energies of Molecular Crystals?

Attaining kJ/mol accuracy in cohesive energy for molecular crystals is a persistent challenge in computational materials science. In this study, we evaluate second-order Møller-Plesset perturbation theory (MP2) and its spin-component scaled models for calculating cohesive energies for 23 molecular crystals (X23 data set). Using periodic boundary conditions and Brillouin zone sampling, we converge results to the thermodynamic and complete basis set limits, achieving an accuracy of about 2 kJ/mol (0.5 kcal/mol), which is rarely achieved in previous MP2 calculations for molecular crystals. When compared to experimental data, our results have a mean absolute error of 12.9 kJ/mol, comparable to Density Functional Theory with the PBE functional and TS dispersion correction. By separately scaling the opposite-spin and same-spin correlation energy components, using predetermined parameters, we reduce the mean absolute error to 9.5 kJ/mol. Further fine-tuning of these scaling parameters specifically for the X23 data set brings the mean absolute error down to 7.5 kJ/mol.

Too big, too small, or just right? A benchmark assessment of density functional theory for predicting the spatial extent of the electron density of small chemical systems.

Multipole moments are the first-order responses of the energy to spatial derivatives of the electric field strength. The quality of density functional theory prediction of molecular multipole moments thus characterizes errors in modeling the electron density itself, as well as the performance in describing molecules interacting with external electric fields. However, only the lowest non-zero moment is translationally invariant, making the higher-order moments origin-dependent. Therefore, instead of using the 3 × 3 quadrupole moment matrix, we utilize the translationally invariant 3 × 3 matrix of second cumulants (or spatial variances) of the electron density as the quantity of interest (denoted by K). The principal components of K are the square of the spatial extent of the electron density along each axis. A benchmark dataset of the principal components of K for 100 small molecules at the coupled cluster singles and doubles with perturbative triples at the complete basis set limit is developed, resulting in 213 independent K components. The performance of 47 popular and recent density functionals is assessed against this Var213 dataset. Several functionals, especially double hybrids, and also SCAN and SCAN0 predict reliable second cumulants, although some modern, empirically parameterized functionals yield more disappointing performance. The H, Li, and Be atoms, in particular, are challenging for nearly all methods, indicating that future functional development could benefit from the inclusion of their density information in training or testing protocols.

Modulating redox homeostasis and cellular reprogramming through inhibited methylenetetrahydrofolate dehydrogenase 2 enzymatic activities in lung cancer.

Recent reports have indicated the role of highly expressed methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) enzyme in cancers, showing poor survival; however, detailed mechanistic insight of metabolic functions of MTHFD2 have not been well-defined. Therefore, we aimed to examine the metabolic functions and cellular reprograming potential of MTHFD2 in lung cancer (LCa). In this study, we initially confirmed the expression levels of MTHFD2 in LCa not only in tissue and OncomineTM database, but also at molecular levels. Further, we reprogrammed metabolic activities in these cells through MTHFD2 gene knockdown via lentiviral transduction, and assessed their viability, transformation and self-renewal ability. In vivo tumorigenicity was also evaluated in NOD/SCID mice. Results showed that MTHFD2 was highly expressed in stage-dependent LCa tissues as well in cell lines, A549, H1299 and H441. Cellular viability, transformation and self-renewal abilities were significantly inhibited in MTHFD2-knockdown LCa cell lines. These cells also showed suppressed tumor-initiating ability and reduced tumor size compared to vector controls. Under low oxygen tension, MTHFD2-knockdown groups showed no significant increase in sphere formation, and hence the stemness. Conclusively, the suppressed levels of MTHFD2 is essential for cellular metabolic reprogramming leading to inhibited LCa growth and tumor aggressiveness.

High-precision iron isotope analysis of whole blood, erythrocytes, and serum in adults.

BACKGROUND: Iron isotopic composition serves as a biological indicator of Fe metabolism in humans. In the process of Fe metabolism, essential carriers of Fe circulate in the blood and pass through storage organs and intestinal absorptive tissues. This study aimed to establish an analytical method for high-precision Fe isotopic measurement, investigate Fe concentration and isotopic composition in different parts of whole blood, and explore the potential of Fe isotopic composition as an indicator for Fe status within individuals. ANALYTICAL METHODS: A total of 23 clinically healthy Taiwanese adults of Han descent were enrolled randomly and Fe isotopic compositions of their whole blood, erythrocytes, and serum were measured. The Fe isotopic analysis was performed by Neptune Plus multiple-collector inductively coupled plasma mass spectrometry with double-spike technique. The precision and reproducibility of the Fe isotopic analysis were monitored by international biological and geological reference materials. MAIN FINDINGS: High-precision Fe isotopic measurements were achieved alongside with high consistency in the isotopic data for well-characterized reference materials. The Fe isotopic signatures of whole blood and erythrocytes were resolvable from that of serum, where both whole blood and erythrocytes contained significantly lighter Fe isotopic compositions compared to the case of serum (P = 0.0296 and P = 0.0004, respectively). The δ56/54Fe value of the serum sample was 0.2‰ heavier on an average than those of whole blood or erythrocytes. This isotopic fractionation observed in different parts of whole blood may indicate redox processes involved in Fe cycling, e.g. erythrocyte production and Fe transportation. Moreover, the δ56/54Fe values of whole blood and serum significantly correlated with the hemoglobin level (P = 0.0126 and P = 0.0020, respectively), erythrocyte count (P = 0.0014 and P = 0.0005, respectively), and Mentzer index (P = 0.0055 and P = 0.0011, respectively), suggesting the Fe isotopic composition as an indicator of functional Fe status in healthy adults. The relationships between blood Fe isotopic compositions and relevant biodemographic variables were also examined. While the average Fe concentration of whole blood was significantly higher in males than in females (P = 0.0028), females exhibited a heavier Fe isotopic composition compared to that of males in whole blood (P = 0.0010) and serum (P < 0.0001). A significantly inverse correlation of the whole blood δ56/54Fe value with body mass index of individuals (P = 0.0095) was also observed. CONCLUSION: The results presented herein reveal that blood Fe isotopic signature is consequentially linked to baseline erythrocyte parameters in individuals and is significantly affected by the gender and body mass index in the adult population. These findings support the role of Fe isotopic composition as an indicator for the variance of Fe metabolism among adult individuals and populations and warrant further study to elucidate the underlying mechanisms.