1. Probing the Internal Dynamics and Shape of Simple Peptides in Urea, Guanidinium Hydrochloride, and Proline Solutions with Time-Resolved Fluorescence Anisotropy and Atomistic Cosolvent Simulations
Gouri S Jas, Ed W Childs, C Russell Middaugh, Krzysztof Kuczera J Phys Chem B. 2021 Oct 7;125(39):10972-10984. doi: 10.1021/acs.jpcb.1c06838. Epub 2021 Sep 24.
Picosecond time-resolved fluorescence anisotropy was used to measure the effect of denaturants and osmolytes on the reorientation dynamics of the simplest dipeptide. The solvent denaturants guanidinium hydrochloride (gdm), urea, and the osmolyte proline were used at several concentrations. Analysis of the concentration dependence of denaturants at a fixed temperature showed faster and slower reorientation time in two different denaturants at a nearly identical solvent viscosity (η). The reorientation time τ significantly deviates from Kramers' theory (τ ∝ η1) in the high friction limit for guanidinium and urea with r ≈ 0.4 and r ≈ 0.6 at pH 7.2, respectively. In proline, τ is nearly proportional to η. Atomistic molecular dynamics simulations of the dipeptide in identical cosolvents showed excellent agreement with the measured rotational orientation time. The dipeptide dihedral (ϕ, ψ) isomerization times in water and 6 M urea are almost identical and significantly slower in guanidinium. If a faster and slower reorientation time can be associated with the compact and expanded shapes, the fractional viscosity dependence for guanidinium and urea may result from the fact that internal dynamics of peptides in these cosolvents involve higher and lower internal friction within the dynamic elements.
2. Synthesis of β-Lactams and β-Homoprolines by Fragmentative Rearrangement of 5-Spirocyclopropaneisoxazolidines Mediated by Acids
Franca M Cordero, Alberto Brandi Chem Rec. 2021 Feb;21(2):284-294. doi: 10.1002/tcr.202000136. Epub 2020 Nov 26.
Azetidinones and β-amino acids serve as useful building blocks in synthetic organic chemistry and their structural motifs are often found in biologically active compounds. Due to the importance of these compounds, several synthetic strategies have been developed and availability of new synthetic approaches is highly desirable. In this account, we describe the development of an original method that allows the preparation of β-lactam and β-homoproline derivatives not easily accessible through traditional processes. The serendipitous discovery made in our lab in 2000 involved the formation of a β-lactam by heating a mixture of an alkylidenecyclopropane tethered to a formyl group with N-methylhydroxylamine hydrochloride. Investigation of the process resulted in disclosing an alternative synthetic method of azetidinones based on an acid induced fragmentative rearrangement of cycloadducts of nitrones with suitable methylenecyclopropane derivatives. Herein, the scope of this process is reviewed. In addition, both experimental and computational studies of the mechanism for this peculiar fragmentative rearrangement are presented.
3. [Determination of stachydrine hydrochloride and leonurine hydrochloride in Yimucao preparations by HPLC-MS]
Chao Zhou, Yi He, Yu-Mei Zhang, Bo Wang, Jian-Dong Yu, Zhong Dai, Shuang-Cheng Ma Zhongguo Zhong Yao Za Zhi. 2016 May;41(10):1876-1879. doi: 10.4268/cjcmm20161019.
To establish the quantitative method of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba. The contents of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba were determined by HPLC-MS. The chromatographic column was Waters XBridge Amide(4.6 mm×250 mm,5 μm). The mobile phase was acetonitrile-0.1% formic acid in gradient mode,at the flow rate of 1.0 mL· min⁻¹,with the split ratio of 1:4. MS conditions for the ESI ion source,positive ion mode,selective ion scan(SIM) of stachydrine hydrochloride(m/z 144.0) and leonurine hydrochloride(m/z 312.0) was measured. The linear ranges of stachydrine hydrochloride was 0.562 8-281.4 μg·L-1(r=0.999 8). The linear ranges of leonurine hydrochloride was 0.521 2-260.6 μg·L-1(r=0.999 8). The method is accurate,simple,and reliable,and can be used to determine the contents of stachydrine hydrochloride and leonurine hydrochloride in the preparations of Leonuri Herba.