Catalytic enantioselection usually depends on differences in steric interactions between prochiral substrates and a chiral catalyst. We have discovered a carbene Si-H insertion in which the enantioselectivity depends primarily on the electronic characteristics of the carbene substrate, and the log(er) values are linearly related to Hammett parameters. A new class of chiral tetraphosphate dirhodium catalysts was developed; it shows excellent activity and enantioselectivity for the insertion of diarylcarbenes into the Si-H bond of silanes. Computational and mechanistic studies show how the electronic differences between the two aryls of the carbene lead to differences in energies of the diastereomeric transition states. This study provides a new strategy for asymmetric catalysis exploiting the electronic properties of the substrates.

Background

Molecular epidemiology can be useful in identifying clusters of human immunodeficiency virus (HIV) transmission that can be targeted for prevention.

Methods

Regular screening of 2000 men who have sex with men (MSM) in Beijing, China, for HIV infection every 2 months identified 179 primary infections (2007-2010). HIV-1 pol sequences were obtained and used to infer the transmission network and identify transmitted drug resistance (TDR) among these individuals. We evaluated the use of clinical and network information to target prevention efforts. Prevention efficiency was calculated as the number of infections saved per number of interventions.

Results

This cohort was infected with HIV-1 subtype B (28%), circulating recombinant form (CRF)_01 AE (53%), and CRF_07 BC (16%). The overall rate of TDR was low (5%), but the rate of clustering was high (64%), suggesting deep sampling of the subnetwork. Provision of a theoretically high-efficacy intervention like antiretroviral therapy to all participants had a prevention efficiency of 23%. The efficiency of targeting prevention based on lower CD4 counts (<200 cells/mL, <350 cells/mL, or <500 cells/mL) and higher viral loads (>100 000 copies/mL and >50 000 copies/mL) was between 10% and 18%. The efficiency of targeting prevention based on number of network connections was much higher (30%-42%). For example, treating the 33 participants with ≥5 connections in 2009 would have theoretically prevented 14 infections in 2010 (42% prevention efficiency).

Conclusions

Regular HIV testing of MSM in Beijing can deeply sample the local transmission subnetwork, and targeting prevention efforts based on network connectivity may be an efficient way to deliver prevention interventions.