3-Ferrocenyl-estra-1,3,5 (10)-triene-17-one: Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT Studies, and Its Binding to Human Serum Albumin Studied through Fluorescence Quenching and In Silico Docking Studies

Mariola M Flores-Rivera; José A Carmona-Negrón; Arnold L Rheingold; Enrique Meléndez

doi:10.3390/molecules28166147

3-Ferrocenyl-estra-1,3,5 (10)-triene-17-one: Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT Studies, and Its Binding to Human Serum Albumin Studied through Fluorescence Quenching and In Silico Docking Studies

Molecules. 2023 Aug 20;28(16):6147. doi: 10.3390/molecules28166147.

Authors

Mariola M Flores-Rivera¹, José A Carmona-Negrón¹, Arnold L Rheingold², Enrique Meléndez¹

Affiliations

¹ Department of Chemistry, University of Puerto Rico, P.O. Box 9019, Mayaguez, PR 00681, USA.
² Department of Chemistry and Biochemistry, University of California-San Diego, Urey Hall 5128, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Abstract

3-ferrocenyl-estra-1,3,5 (10)-triene-17-one (2), [Fe(C₅H₅)(C₂₄H₂₅O₃)], crystallizes in the monoclinic space group C2. The cyclopentadienyl (Cp) rings adopt a nearly eclipsed conformation, and the Cp plane is tilted by 87.66° with respect to the substituted phenyl plane. An average Fe-C(Cp) bond length of 2.040(13) Å was determined, similar to the one reported for ferrocene. Hirshfeld surfaces and two-dimensional fingerprint plots were generated to analyze weak intermolecular C-H···π and C-H···O interactions. Density functional theory studies revealed a 1.15 kcal/mol rotational barrier for the C3-O1 single bound. Fluorescence quenching studies and in silico docking studies suggest that human serum albumin forms a complex with 2 via a static mechanism dominated by van der Waals interactions and hydrogen bonding interactions.

Keywords: DFT; Hirshfeld surface; crystal structure; ferrocene; fluorescence quenching.

MeSH terms

Fluorescence
Humans
Hydrogen Bonding
Research*
Serum Albumin, Human*

Substances

Serum Albumin, Human

Grants and funding

This research was funded by the Bridge to the Doctorate Program, grant number NSF HRD-1826558; the BioXFEL Science Technology Center, grant number STC A.N 1231306; and the Alfred P. Sloan Foundation—UPRM Ph.D. Enrichment Program, grant number G-2018-11025.