Steroid Hormone Androsterone Observed in the Gas Phase by Rotational Spectroscopy

Abstract

We report the investigation of the steroid hormone androsterone in the gas phase. Androsterone is a male sex steroid hormone, being the first steroid hormone from this category isolated and discovered 90 years ago. Despite the chemical compositions of steroids being well-known since long ago, studying their structures in the gas phase is still a challenging task, and to date, just a handful of detailed experimental structures for steroids have been reported. The rotational spectrum of androsterone was recorded in the 2−8 GHz frequency region with a broadband chirped-pulse Fourier transform microwave spectrometer coupled with supersonic expansion. From the weak rotational spectrum, one conformer has been detected in the isolated and cold conditions of the molecular jet. The combination of the experimental results with quantum chemical calculations allowed us to unambiguously identify the conformation of androsterone in the gas phase.Letter pubs.acs.org/JPCL

Quantum chemistry meets high-resolution spectroscopy for characterizing the molecular bricks of life in the gas-phase

“…[44][45][46][47][48][49] Unfortunately, equilibrium geometries and vibrational frequencies can benefit only marginally from these developments, which have not yet been extended to analytical energy derivatives. However, the intrinsic errors affecting the standard methods employed in the current spectroscopic studies (typically second-order Møller-Plesset perturbation theory (MP2) 50 or hybrid density functionals) [51][52][53][54] hamper any a priori prediction of the spectroscopic outcome. Therefore, the current practice is to resort to a posteriori interpretations in terms of the agreement between experimental and computed spectroscopic parameters, irrespective of the computed stability of the selected species.…”

Hunting for Complex Organic Molecules in the Interstellar Medium: The Role of Accurate Low-Cost Theoretical Geometries and Rotational Constants

“…However, as the dimensions of the molecule increase, the spectral congestion grows due to both intrinsic factors and the presence of different low-energy species separated by sufficiently high-energy barriers to avoid their interconversion under the experimental conditions. , Quantum chemical (QC) computations play a fundamental role in the disentanglement of these complexities, but the accuracy requirements of rotational spectroscopy are very stringent. As a consequence, state-of-the-art methods are needed, which are, unfortunately, applicable to systems containing at most a dozen atoms. − For larger systems, the current standard is to use B3LYP or MP2 computations with medium-size basis sets. − However, the intrinsic errors of these approaches (0.5–1%) are too large to allow unbiased analyses without additional experimental pieces of information (e.g., quadrupole coupling constants in the presence of nuclei, in which they do not vanish) . Improved results can be obtained correcting the density functional theory (DFT) geometrical parameters by bond-specific parameters derived from a large database of accurate molecular structures , [the so-called linear regression (LR) approach], or with reference to suitable fragments whose accurate geometries are already known [the so-called template molecule (TM) approach] .…”

Accurate Structures and Rotational Constants of Steroid Hormones at DFT Cost: Androsterone, Testosterone, Estrone, β-Estradiol, and Estriol

“…The rotational spectrum of androsterone (3α-hydroxy-5α-androstan-17-one, A1) has been recorded in the 2–8 GHz region by Caliebe et al A systematic search of low-energy structures evidenced the presence of chair ( 3 C 10 ) and half-chair ( 4 H 5 ) arrangements of the A ring, which were referred to as androsterone and p-androsterone, respectively, in ref . For each of those structures, the rotation around the C3–O bond can generate anti ( a ), gauche (+) ( gp ), and gauche (−) ( gm ) rotamers (referred to as the C 4 –C 3 –O–H dihedral angle).…”

“…The structures of the low-energy minima of androsterone, testosterone, estrone, and β-estradiol reported in previous studies − , were used as starting points for full geometry optimizations at the rDSD level. On the other hand, the starting structures for estriol were obtained from those of β-estradiol by enforcing staggered conformations of its additional OH moiety.…”

“…Thanks to all of these developments, it should be, in principle, possible to obtain equilibrium structures and ground state rotational constants of unprecedented accuracy for large molecules. The new tool has been validated by a systematic investigation of several steroid hormones (androsterone, testosterone, estrone, and β-estradiol), whose experimental MW spectra have been recorded in the last six years. − Such hormones, belonging to androgen and estrogen families, have a wide biological activity in the human body, are biosynthesized from cholesterol, and have a common semirigid backbone with different substituents . We also analyzed estriol (another estrogen), whose structure and spectroscopic parameters have not yet been reported.…”