2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone: UV Photoinitiator & Biological Activity

2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone is a highly efficient UV curing agent which is used to initiate the photopolymerisation of chemically prepolymers – e.g. acrylates – in combination with mono- or multifunctional monomers. 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone is especially suitable for pigmented UV curable systems, photoresists and printing plates.

Donor–acceptor complexes between photoinitiators and photoresist

Additive manufacturing via multi-photon polymerisation (MPP) became a powerful microfabrication technique, where tightly focused femtosecond laser pulses initiate localised polymerisation within photosensitive materials, allowing for precise, direct-write fabrication of high-resolution three-dimensional (3D) architectures. SZ2080™ sensitised with common photoinitiators IRG369 [2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone] and BIS [4,4′-bis(diethylamino)benzophenone, Michler's ketone] shows exceptionally rapid and efficient photopolymerisation. Additionally, these photosensitive mixtures show unusual changes of UV/Vis absorption and emission. Although these changes have been observed and documented, no clear link between spectral changes and polymerisation parameters has been established so far. Understanding this phenomenon is crucial, as it could lead to new potential functionalities, improved process maintenance, and expanded capabilities for hybrid resin-based systems in advanced MPP. Therefore, in this work, we present a systematic study of SZ2080™ with the incorporation of 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and BIS photoinitiators to elucidate their coordination behaviour in the organic–inorganic prepolymer.[1]

The resolution bridges were fabricated to assess the laser fabrication window as well as the dynamic fabrication window (DFW) of sensitised SZ2080™ with 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and BIS PIs. The particular data indicates that BIS allows to fabricate 3D structures even at lower Ith – 0.55 TW cm−2 intensities, while for 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone, Ith is equal to 1.46 TW cm−2. Both BAPO and TPO need quite a bit higher intensities for line fabrication with threshold intensities equaling to 2.19 and 2.74 TW cm−2, respectively. Comparing the broadness of DFWs, BIS and IRG369 possess the highest values of 3.5 and 1.63, respectively, compared to BAPO and TPO, which feature only 0.75 and 0.4, respectively. MPP indicates an unusual behaviour of 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and BIS PIs that enhance the photopolymerisation window. The DFW in both PIs’ cases was significantly improved compared to using BAPO and TPO. To learn about those reasons, the ground-state absorption and steady-state fluorescence spectra of the corresponding samples were measured. The spatial separation of the electron-donating groups in BIS sterically restricts it to binding strictly as a weaker, monodentate ligand. This fundamental difference in coordination geometry perfectly explains the greater thermodynamic stability (reflected in the higher binding affinity) of the IRG369 complex.

In conclusion, the results presented in this study have established a clear link between the fabrication window and the formation of ground-state complexes between SZ2080™ prepolymer and electron rich 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and BIS photoinitiators. The totality of spectroscopic structural data points towards the formation of a donor–acceptor complex between the Zr–Si–O chain in the SZ2080™ prepolymer, and the Lewis basic NR2 or C  O atoms of the PI. We suggest that the improvement of polymerisation performance is due to elimination of diffusion-limited reaction steps between the SZ2080™ prepolymer and the PIs. Since the ground state complexes are readily observed by their characteristic changes in the optical spectra, the presence of such changes could be used as a guide in design and testing of new material combinations for MPP. Our study thus opens avenues for further exploration of hybrid organic–inorganic materials in additive manufacturing, highlighting the role and importance of coordination between PI and resin, towards optimising photopolymerisation processes.

2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone as novel environmental androgens

In this study, we used environmental and industrial compounds in the molecular docking analysis with AR-LBD. More than a dozen compounds with predicted high binding affinity to AR-LBD were identified. Then we tested their androgenic effect with in vitro androgen-sensitive cell proliferation assays, luciferase reporter gene assays and in vivo animal study with immature male rats. Two compounds were found, for the first time, to have prominent androgenic activity both in vitro and in vivo, namely Irgacure 369 (2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone), abbreviated as IC-369, a photoinitiator in the packaging  and galaxolide. Many industrial chemicals have been characterized as endocrine disruptors, and they can interfere with estrogen or androgen receptor signaling. In this study, we found two environmental androgens 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and HHCB, which are common industrial and environmental compounds people are frequently exposed to. HHCB has been shown to have weak estrogenic effects (Schreurs et al., 2002; Wang et al., 2007), however, there are no reports on the effects of IC-369 and HHCB on AR signaling. Therefore, this study provided new evidences for the androgenic effect of 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and HHCB through binding and activating AR.[2]

It is well known that the prostate and seminal vesicle are androgen-dependent secretory glands in the male reproductive tract. Then we investigated the effects of IC-369 and HHCB on the reproductive organ development of immature rats. Animal experiments showed that 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and HHCB could promote the growth of seminal vesicle tissue in the male reproductive system, which was confirmed by histopathological results. Consistently, we found that the expression levels of MKI67 and PCNA proteins in IC-369 and HHCB experimental groups were higher than those in the control group. However, although the expression level of MKI67 and PCNA protein in the prostate of IC-369 group was higher compared with the control group, the gland lumen of the prostate of IC-369 group was smaller. To further study the gene expression change induced by IC-369 and HHCB in seminal vesicle tissue, RNA-sequencing and qPCR analysis were performed. Transcriptomic technology was used to analyze the global change of gene expression in rat seminal vesicle tissue after exposure to 2-Benzyl-2-(dimethylamino)-4'-morpholinobutyrophenone and HHCB. The results showed that the expression levels of more than 4000 genes in rat seminal vesicles changed after exposure to IC-369 and HHCB. It is not surprising that IC-369 and HHCB altered expression of many more genes than testosterone since IC-369 and HHCB may act on more targets other than AR.

References

[1]Navickas M, Ladika D, Orentas E, Talaikis M, Niaura G, Grigalavičius M, Gaidys M, Fernández-Terán RJ, Malinauskas M, Vengris M. Donor-acceptor complexes between photoinitiators and hybrid organic-inorganic SZ2080™ photoresist. Mater Adv. 2026 Mar 13. doi: 10.1039/d5ma01526j. Epub ahead of print. PMID: 41858592; PMCID: PMC12998534.

[2]Li, Mingzhao et al. “Galaxolide and Irgacure 369 are novel environmental androgens.” Chemosphere vol. 324 (2023): 138329. doi:10.1016/j.chemosphere.2023.138329

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