A Quantum-Guided Molecular Mechanics Force Field for the Ferrocene Scaffold.

Ferrocene derivatives have a wide range of applications, including as ligands in asymmetric catalysis, due to their chemical stability, rigid backbone, steric bulk, and ability to encode stereochemical information via planar chirality. Unfortunately, few of the available molecular mechanics force fields incorporate parameters for the accurate study of this important building block. Here, we present a MM3* force field for ferrocenyl ligands, which was generated using the quantum-guided molecular mechanics (Q2MM) method. Detailed validation by comparison to DFT calculations and crystal structures demonstrates the accuracy of the parameters and uncovers the physical origin of deviations through excess energy analysis. Combining the ferrocene force field with a force field for Pd-allyl complexes and comparing the crystal structures shows the compatibility with previously developed MM3* force fields. Finally, the ferrocene force field was combined with a previously published transition-state force field to predict the stereochemical outcomes of the aminations of Pd-allyl complexes with different amines and different chiral ferrocenyl ligands, with an R2 of ∼0.91 over 10 examples.

Case series analysis of hindfoot injuries sustained by drivers in frontal motor vehicle crashes.

Improvements to vehicle frontal crashworthiness have led to reductions in toe pan and instrument panel intrusions as well as leg, foot, and ankle loadings in standardized crash tests. Current field data, however, suggests the proportion of foot and ankle injuries sustained by drivers in frontal crashes has not decreased over the past two decades. To explain the inconsistency between crash tests results and real world lower limb injury prevalence, this study investigated the injury causation scenario for the specific hind-foot injury patterns observed in frontal vehicle crashes. Thirty-four cases with leg, foot, and ankle injuries were selected from the Crash Injury Research and Engineering Network (CIREN) database. Talus fractures were present in 20 cases, representing the most frequent hind-foot skeletal injuries observed among the reviewed cases. While axial compression was the predominant loading mechanism causing 18 injuries, 11 injured ankles involved inversion or eversion motion, and 5 involved dorsiflexion as the injury mechanism. Injured ankles of drivers were more biased towards the right aspect with foot pedals contributing to injuries in 13 of the 34 cases. Combined, the results suggest that despite recent advancement of vehicle performance in crash tests, efforts to reduce axial forces sustained in lower extremity should be prioritized. The analysis of injury mechanisms in this study could aid in crash reconstructions and the development of safety systems for vehicles.

Analysis of crash parameters and driver characteristics associated with lower limb injury.

This study aims to investigate changes in frequency, risk, and patterns of lower limb injuries due to vehicle and occupant parameters as a function of vehicle model year. From the National Automotive Sampling System-Crashworthiness Data System, 10,988 observations were sampled and analyzed, representing 4.7 million belted drivers involved in frontal crashes for the years 1998-2010. A logistic regression model was developed to understand the association of sustaining knee and below knee lower limb injuries of moderate or greater severity with motor vehicle crash characteristics such as vehicle type and model years, toepan and instrument panel intrusions in addition to the occupant's age, gender, height and weight. Toepan intrusion greater than 2cm was significantly associated with an increased likelihood of injury (odds ratio: 9.10, 95% confidence interval 1.82-45.42). Females sustained a higher likelihood of distal lower limb injuries (OR: 6.83, 1.56-29.93) as compared to males. Increased mass of the driver was also found to have a positive association with injury (OR: 1.04, 1.02-1.06), while age and height were not associated with injury likelihood. Relative to passenger cars, vans exhibited a protective effect against sustaining lower limb injury (OR: 0.24, 0.07-0.78), whereas no association was shown for light trucks (OR: 1.31, 0.69-2.49) or SUVs (OR: 0.76, 0.28-2.02). To examine whether current crash testing results are representative of real-world NASS-CDS findings, data from frontal offset crash tests performed by the Insurance Institute for Highway Safety (IIHS) were examined. IIHS data indicated a decreasing trend in vehicle foot well and toepan intrusion, foot accelerations, tibia axial forces and tibia index in relation to increasing vehicle model year between the year 1995 and 2013. Over 90% of vehicles received the highest IIHS rating, with steady improvement from the upper and lower tibia index, tibia axial force and the resultant foot acceleration considering both left and right extremities. Passenger cars received the highest rating followed by SUVs and light trucks, while vans attained the lowest rating. These results demonstrate that while there has been steady improvement in vehicle crash test performance, below-knee lower extremity injuries remain the most common AIS 2+ injury in real-world frontal crashes.

Stereoselectivity in Asymmetric Catalysis: The Case of Ruthenium-Catalyzed Ketone Hydrogenation.

The ruthenium-catalyzed asymmetric hydrogenation of simple ketones to generate enantiopure alcohols is an important process widely used in the fine chemical, pharmaceutical, fragrance, and flavor industries. Chiral diphosphine-RuCl2-1,2-diamine complexes are effective catalysts for the reaction giving high chemo- and enantioselectivity. However, no diphosphine-RuCl2-1,2-diamine complex has yet been discovered that is universal for all kinds of ketone substrates, and the ligands must be carefully chosen for each substrate. The procedure of finding the best ligands for a specific substrate can be facilitated by using virtual screening as a complement to the traditional experimental screening of catalyst libraries. We have generated a transition state force field (TSFF) for the ruthenium-catalyzed asymmetric hydrogenation of simple ketones using an improved Q2MM method. The developed TSFF can predict the enantioselectivity for 13 catalytic systems taken from the literature, with a mean unsigned error of 2.7 kJ/mol.