Highlights Patients were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5-21 days  Our study shows that oral arbidol and LPV/r in the combination group is associated with a significant elevated negative conversion rate of coronavirus' test in 7-day and 14-day, compared with LPV/r only in the monotherapy group. Combination therapy is associated with a significantly improved the chest CT scans in 7-day. We suppose that reducing the viral load as soon as possible could benefit the delay of the progression of lung lesions. Abstract BackgroundCorona Virus Disease 2019 (COVID-19) due to the 2019 novel coronavirus (SARS-CoV-2) emerged in Wuhan city and rapidly spread throughout China. We aimed to compare arbidol and lopinavir/ritonavir(LPV/r) treatment for patients with COVID-19 with LPV/r only. MethodsIn this retrospective cohort study, we included adults (age≥18years) with laboratory-confirmed COVID-19 without Invasive ventilation, diagnosed between Jan 17, 2020, and Feb 13, 2020. Patients, diagnosed after Jan 17, 2020, were given oral arbidol and LPV/r in the combination group and oral LPV/r only in the monotherapy group for 5-21 days. The primary endpoint was a negative conversion rate of coronavirus from the date of COVID-19 diagnosis(day7, day14), and assessed whether the pneumonia was progressing or improving by chest CT (day7). ResultsWe analyzed 16 patients who received oral arbidol and LPV/r in the combination group and 17 who oral LPV/r only in the monotherapy group, and both initiated after diagnosis. Baseline clinical, laboratory, and chest CT characteristics were similar between groups. The SARS-CoV-2 could not be detected for 12(75%) of 16 patients' nasopharyngeal specimens in the combination group after seven days, compared with 6 (35%) of 17 in the monotherapy group (p<0·05). After 14 days, 15 (94%) of 16 and 9 (52·9%) of 17, respectively, SARS-CoV-2 could not be detected (p<0·05). The chest CT scans were improving for 11(69%) of 16 patients in the combination group after seven days, compared with 5(29%) of 17 in the monotherapy group (p<0·05). ConclusionIn patients with COVID-19, the apparent favorable clinical response with arbidol and LPV/r supports further LPV/r only.

The role of the bulky ligands in Ni(II) diimine catalyzed ethylene polymerization has been examined with a combined density functional theory quantum mechanics and molecular mechanics (QM/MM) model. Specifically, we have examined the catalytic center of the type (ArNC(R)−C(R)NAr)NiII-R‘+, where R = Me and Ar = 2,6-C6H3(i-Pr)2. The Ar and R groups were treated by a molecular mechanics force field while density functional theory was applied to the remainder of the system. The chain propagation, chain branching, and chain termination processes have been investigated with the hybrid method and found to have barriers of ΔH ⧧ = 11.8, 15.3, and 18.4 kcal/mol, respectively, which is in excellent agreement with experiment in both absolute and relative terms. This is in stark contrast to the pure QM model in which the influence of the bulky Ar and R groups was neglected and the established order of the barriers is not even reproduced. The role played by the bulky substituents is dual in nature. First, the Ar and R groups act to sterically hinder the axial coordination sites of the Ni center. This has the most dramatic destabilizing effect on the resting state and termination transition states, in which both axial positions are occupied. In addition to the steric factor, we find that the electronic preference for the aryl rings to orient themselves in a coplanar fashion with the diimine ring results in a stabilization of the insertion transition state relative to the resting state. These two factors act to both lower the propagation barrier and increase the termination barrier compared to the “naked” pure QM model system.

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We have applied a nonlocal density functional method to the study of ethylene polymerization with a Ni(II) catalytic center coordinated to diimine (HNdCH-CHdNH). We have investigated chain initialization, chain propagation, as well as chain isomerization and chain termination. Chain initialization proceeds in a stepwise fashion, with an overall activation barrier of 11.1 kcal/mol. Chain propagation can proceed via two different pathways, which have similar activation energies (16.8 and 17.5 kcal/mol, respectively). In contrast to behavior observed for metallocene catalysts, none of the insertion transition states show agostic stabilization. The activation energy for chain isomerization is 12.8 kcal/mol, which proceeds via a concerted mechanism, rotating the chain and simultaneously abstracting the -agostic hydrogen. Chain termination occurs via a stable hydride intermediate, which is formed with a barrier of 9.7 kcal/mol and decays into the termination product with a small activation energy of 1.7 kcal/mol. Production of experimentally observed high molecular weight polymers can only be explained by suppression of the chain termination transition state due to sterically demanding substituents on the diimine ligand.

The first implementation of the intrinsic reaction coordinate (IRC) method within the density functional theory (DFT) framework is presented. The implementation has been applied to four different types of chemical reactions represented by the isomerization process, HCN = HNC (A); the sN2 process, H-+ CH4 = CH4 + H -(B); the exchange process, H . + H X = H X + H. (X = F,CI) (C); and the elimination process, C~HSCI = C2H4 + HC1 (D).The present study presents for each process optimized structures and calculated harmonic vibrational frequencies for the reactant(s), the transition state, and the product(s) along with the IRC path connecting the stationary points. The calculations were camed out within the local density approximation (LDA) as well as the L D~N L scheme where the LDA energy expression is augmented by Perdew's and Becke's nonlocal (NL) corrections. The LDA and L D~N L results are compared with each other as well as the best available ab initio calculations and experimental data. Fot reaction (D), ab initio calculations based on MP2 geometries and MP4SDTQ energies have been added due to the lack of accurate published POSt-HF calculations on this process. A detailed discussion is provided on the efficiency of the IRC algorithms, the relative accuracy of the DFI and ab initio schemes, as well as the reaction mechanisms of the four reactions. It is concluded that the L D~N L scheme affords the same accuracy as does the MP4 method. The post-HF methods seem to overestimate activation energies, whereas the corresponding L D~N L estimates are too low. The LDA activation energies are even lower than the L D~N L counterparts. The incorporation of the IRC method into the D F~ framework provides a promising and reliable tool for probing the chemical reaction path on the potential energy surfaces, even for large-size systems. IRC calculations by ab initio methods of an accuracy similar to the L D~N L scheme, such as the M P~ scheme, are not feasible.