Fast UV‐ and Visible Light Induced Polymer Network Formation Using Carbene Mediated CH‐insertion Based Crosslinking (CHic) Via Nitrophenyl Diazo Esters

The synthesis and characterization of highly photosensitive coatings containing a diazo‐based crosslinker that exhibits high photoreactivity in the near‐visible UV and toward sunlight is present. Nitrophenyl diazo ester (nitroPEDAz) moieties are incorporated into polymer chains via free radical polymerization and generate upon irradiation carbenes, which undergo a CH insertion‐based crosslinking (CHic) reaction. The copolymers are deposited onto substrate surfaces through known coating techniques and then activated to form polymer networks and simultaneously attach covalently to the surfaces if CH groups are available. It is demonstrated that very low light doses on the order of 20 mJ cm−2 are sufficient to generate surface‐attached networks and that the copolymer can be patterned photolithographically into defined structures on a broad spectrum of substrates using UV‐ and natural sunlight. Even a few seconds of sunlight exposure are sufficient to crosslink and surface‐attach the film.


Introduction
The interaction between a material and its environment is mainly influenced by the surface chemistry and physics of the material. [1] To achieve the desired properties, surfaces can be modified by choosing from a wide range polymer coatings. One commonly followed pathway to generate stable coatings is to generate thin film polymer networks and attach them to the surfaces to be modified. This allows the generation of DOI: 10.1002/admi.202300316 surfaces with unique properties such as protein repellency, [2,3] bio functionalization, [4,5] and improvement of frictional properties. [6] Such covalently bonded coatings exhibit higher mechanical and chemical stability compared to coatings deposited by physical techniques. [7] Due to their unique properties surface attached polymer networks open the field for a broad spectrum of applications including photolithography [8,9] or biomedical applications. [5,10] Popular techniques to form polymer networks are bulk polymerization of multifunctional monomers [11] or the crosslinking of prepolymers carrying functional groups. [12,13] Commonly used in the latter case are the vulcanization of rubbers, the direct activation of functional groups in a polymer chain such as the [2+2] cycloaddition reaction of cinnamates [14] and coumarins, [15] by click chemistry, [13,16] and crosslinking by polymerization of acrylic side chains using photoinitiators. [5,17,18] Although these methods are well established, they also have some disadvantages. All these strategies require external additives to crosslinking, which in turn requires additional reaction and purification steps. Such additives tend to remain in the network and change the bulk properties of the polymer or migrate to the surface, where they can alter the properties. [19,20] In addition, these methods require a high density of functional groups to form the properly crosslinked systems.
The C,H-insertion based crosslinking (CHic) method represents an alternative for crosslinking of prepolymers. Here, dormant crosslinker molecules are statistically incorporated into polymer chains through copolymerization or polymeranalogous reactions and activated on demand by photochemical or thermal energy to form a covalent bond with any C-H-group in their vicinity. Compared to standard post-crosslinking methods, the CHicreaction does not require additives. A low density of crosslinkers (in some cases even below 1%) is sufficient due to the abundance of C-H groups in polymers, and the reaction can be carried out in the presence of ambient air. In addition, the crosslinking can be performed in the glassy state, which is advantageous for many applications. These networks can also be covalently attached to the surface when applied to a substrate containing C-H-groups, which is difficult to achieve by conventional methods. [4,7,21,22] www.advancedsciencenews.com www.advmatinterfaces.de Most common UV-crosslinkers or photoinitiators induce crosslinking by high-energy UV-light or require prolongated exposure at higher wavelengths. [7,[23][24][25] Short wavelength UV-light is known to break chemical bonds and damage the polymers. [20] Although low-energy UV light is generally less harmful in this respect, excessive exposure can still cause damage to systems used in biological applications. [5,17,24] It is therefore desirable to have a crosslinking system that forms the network using low-energy UV-light with very short exposure doses or even light in the visible range. [23,26,27] An additional advantage of the use of visible light is its usually greater penetration depth compared to UVlight, which allows that even rather thick films can be cured. [17,23] In recent years CHic crosslinkers on the bases of anthraquinones and thioxanthones have been developed that shifted activation from high-energy to low-energy UV-light, but the required dose for network formation and the complicated synthesis pathway limits their use. [23,27,28] To develop a low-energy UV-vis crosslinker we chose diazobased CHic chemistry. The synthesis of the diazo-group is simple and inexpensive, making it an attractive candidate for such reactions. [29][30][31] Diazo-crosslinkers lose nitrogen after thermal or photochemical activation, forming a reactive carbene. This carbene is capable of inserting into practically any C-H-group to create a crosslinking point by forming a new C-C-and a C-H bond (Scheme 1A). [7,22,32] The reactivity of the diazo-group depends highly on the chemical nature of the neighboring groups. [29,33] This can be used to selectively change the activation parameters through molecular design.
Our approach is to modify the diazo crosslinker PEDAz [22] (a compound carrying a phenyl ester diazo group), in which the diazo-group is adjacent to an ester-group and an aromatic ring, targeting the aromatic system. As the diazo functionality is an electron donor for the aromatic system, adding an electron acceptor, e.g., a nitro group, in the para position should lead to a push-pull effect that redshifts the absorption into the visible light region (Scheme 1B). [34] Here we describe the synthesis and copolymerization of nitroPE-DAz, the photoactivity in the long wavelength UV-and visible region, and the ability to form (surface attached) polymer networks through irradiation at 365 nm and by exposure to sunlight.

Results and Discussion
The UV-vis crosslinker nitroPEDAz was prepared by a simple two-step synthesis ( Figure 1A). The first step follows an esterification reaction procedure developed by Lutjen et al. [35] between 2-hydroxyethyl methacrylate and 4-nitrophenylacetic acid. The diazo group was introduced on the methylene active group next to the ester group via a Regitz diazo transfer reaction. [31] To obtain statistical copolymers, free radical polymerization was carried out with nitroPEDAz and N,N-dimethyl acrylamide (DMAA), which serves as the polymer matrix. The polymerization was initiated by an azo-initiator, namely 2,2'azobis(4-methoxy-2,4-dimethyl valeronitrile) (AMDVN) at 30°C. The low polymerization temperature avoids any premature thermal decomposition of the diazo group during polymerization. NitroPEDAz was copolymerized with a variety of different monomers including methyl methacrlytae (MMA), n-butyl acrly-Scheme 1. A) Schematic depiction of C-H insertion based crosslinking to form surface attached polymer networks using diazo crosslinkers. After the prepolymer is applied to a C-H group-containing surface, the copolymer can be thermally or photochemically activated to form crosslinks between the chains and simultaneously bond to the surface. B) To redshift the CHic reaction, a nitro-group is added in para position to the diazo group on the aromatic ring to create a push-pull effect. The diazo functionality serves as the donor. ate (nBA), and N-isopropyl acrylamide (NIPAM). Characterization of formed copolymers can be found in the Supporting Information. The copolymers had typically molecular weights of around 50-80 kg mol −1 (M n ), and a crosslinker contents of 7%, so that the polymers carried on average 30-50 crosslinker units per chain.
We propose that the photochemical activation of nitroPEDAz containing polymers leads to a carbene which inserts into a C-H bond to form crosslinks. The C-H insertion reaction is a wellknown reaction pathway of carbenes and may occur in the singlet or triplet state. [36,39] Carbenes that result from an adjacent nitrophenyl group are likely to react via the triplet state. [36,37] However, the chemical environment (which is in this case the polar amide group containing polymer matrix) can influence the ground state of such carbenes. [38] However, as both reactions lead to C-H insertion, surface-attached polymer networks form regardless of the electronic state of the carbene.
The reactivity of any photochemical system depends on the absorption wavelength and the molar extinction coefficient. The crosslinker should preferably exhibit strong absorption in the low-energy UV or visible light range. Figure 1B shows the UVvis absorption spectra of the unsubstituted crosslinker PEDAz [22] and the nitro-substituted nitroPEDAz. The addition of the nitro group leads to a bathochromic shift in the absorption maximum from max = 249 nm to max = 338 nm due to the pushpull effect caused by the diazo group (donor) and the nitro group (acceptor). [34] The molar extinction coefficients were calculated at 338 nm (maximum), at 365 nm (UV light source) and at 400 nm.
The absorption of nitroPEDAz in the visible region is higher than that of commercially available photoinitiators (e.g., Irgacure 2959) [24] and is comparable to other known visible light initiators reported in the literature. [26] The kinetics of photoinduced diazo activation was measured via FTIR-spectroscopy using a 365 nm UV source and a solar panel simulating sunlight (details are described in the Supporting Information). The decay kinetics of the diazo group determined from the decrease of the integral of the diazo absorption band at 2100 cm −1 follows an exponential curve in both cases as shown in Figure 2A,C. The half-life dose of the activation at 365 nm was determined to 35 mJ cm −2 , which corresponded to a half-life time of 16.7 s for the light source used. After 200 mJ cm −2 (95.2 s), all diazo groups have reacted and no signal due to the diazo groups can be detected using infrared and UV spectroscopy (see Supporting Information). This corresponds to a 300-fold increase in reactivity compared to the unsubstituted crosslinker. [22,4,27] The decay kinetic by simulated sunlight gave a half-life dose of 291 mJ cm −2 with a half-life time of 2.9 s. After 1200 mJ cm −2 (120 s), no diazo-group was detectable. The higher dose required for sunlight exposure compared to UV crosslinking is expected, given the difference in the molar extinction coefficients. However, the (simulated) sunlight has a higher light intensity than the UV source, so the half-life times are shorter.
The decay kinetics of the diazo groups as obtained by the infrared spectra show how fast the carbenes form. The kinetics of the subsequent crosslinking reaction is then determined by gel-content experiments. The UV source at 365 nm and the solar panel were used again for this purpose. In addition to these two irradiation experiments, a measurement was performed, in which a UV filter was installed in the solar panel so that only visible light above 400 nm could reach the copolymer film and any UV light was blocked out, simulating an in-door experiment. The gel-content measurements are shown in the graphs in Figure 2B,D (details in the Supporting Information). The kinetics of gel-formation is typical of a percolation process. This can be seen in the induction phase before reaching the percolation point. [28,40] Once the percolation point is reached, it is followed by a steady increase of the gel contents. Note, that the percolation point (critical dose ≈0.8 mJ cm −2 ) is reached even though less than 5% of the diazo moieties have been activated. This low conversion is sufficient due to the large number of diazo groups per polymer chain. Irradiation with 365 nm light leads to high gel contents after 20 mJ cm −2 (10 s) with a sensitivity of d 0.5 = 2.2 mJ cm −2 , comparable to literature values for good photoresist materials. [9] Network formation under simulated sun-light takes below 1 s to reach percolation and 3 s to reach 100% gel-content. Suninduced crosslinking could be of interest for coating and curing of large area substrates. Even UV filtered sunlight resulted in high gel-contents after 30 s. The slower kinetics is expected as the strongly absorbing UV light is blocked out. For sensitive applications where the use of high-energy UV light is not an option, or for the coating of UV-protected materials, this crosslinking method could be an attractive option.
As demonstration cases, we investigated the ability of the copolymer to act as a negative photoresist and tested the protein repellency of a surface-attached hydrogel microstructure generated by sunlight. [3,41] To fabricate the structures, a photomask was used, which is shown schematically in Figure 3A. The microscope image of the selected structure in the photomask is shown in Figure 3B. It has a width of 1324 μm, height of 1570 μm, and line widths of 5 − 10 μm. The image was patterned with UV-light ( Figure 3C, 10 mJ cm −2 ), the solar panel ( Figure 3D, 3 s) and with natural sunlight outside the laboratory ( Figure 3E, 1 s). The line width was slightly broadened compared to the mask, but overall the structures showed good resolution.
To create a protein repellent surface, an untreated PMMA slide was spray-coated with the copolymer. Crosslinking was performed by the solar panel (3 s) using a photomask. The formed structure on the PMMA slide was incubated with fluorescent anithuman-IgA-Alexa647. The irradiated areas where surfaceattached polymer network was deposited showed almost no fluorescence signal because the entropic shielding of the hydrogel prevents the attachment of proteins. [3] The rest of the PMMA slide, where no polymer became attached and all the deposited material was washed away during extraction, showed adsorption of the fluorescently labeled proteins as shown in the fluorescence images in Figure 3F. In general, defined structures could be produced by photolithography with a low and cost saving energy dose on silicon substrates modified by a self-assembled layer of silanes.
To demonstrate that the surface attachment is universal and can be applied to any C-H containing polymer substrates, we additionally coated a polyethylene (PE) and a polystyrene (PS) substrate as examples for technical, hard to modify substrates, and in addition a polyether ether ketone (PEEK) substrate as this polymer has only aromatic C-H bonds, with P(DMAA-co-nitroPEDAz). After irradiation and careful extraction, we measured the contact angle (CA) after exposure and extraction and x-ray photoelectron spectroscopy, XPS (details in the Supporting Information). For all substrates, the copolymer was still present, which was evidenced by the CA of the surface compared to the unmodified substrates and the nitrogen signal in the XP spectra (resulting mostly from the amide group in the copolymer). Whereas on PE, PS, and PEEK the CA was ≈80°, the water droplet spread on the surface-attached PDMAA network layer.

Conclusion
NitroPEDAz group containing polymers allow the rapid and facile formation of surface attached networks for coating and patterning of a broad spectrum of surfaces including nonfunctionalized polymeric substrates using low-dose near visible UV-or sunlight. With this, photolithographic patterning or protein repellent surface coatings can be produced in a few seconds. The rapid photochemical modification is possible due to the molecular design of the nitrophenyl diazo ester crosslinker, which exhibits strong absorption in the long wavelength UV range causing rapid carbene formation. The high sensitivity of nitroPEDAz allows the generation of polymer networks by mild activation, including ambient sunlight. These lowdose and environmentally friendly activation parameters are a new benchmark for the formation of polymer networks from processable prepolymers using CHic chemistry and compare favorably to resins described in the literature. Such systems could be useful for coating and curing large areas or when a UV-sensitive substrate needs to be coated and are potentially very attractive candidates for biotechnological applications, as low-dose activation does not compromise biomolecules and their functions.

Supporting Information
Supporting Information is available from the Wiley Online Library or from the author.