Augusto C. Tomé

Pyrenylimidazolyl-functionalized free-base phthalocyanines (H2Pc) and their zinc complexes (ZnPc) constitute multifunctional building blocks for realizing heterostructures with liquid phase exfoliated transition-metal dichalcogenides (LPE-TMDs). Here, we report the synthesis, optical features, and excited-state characterization of three different phthalocyanines, namely H2Pc 4, ZnPc 5, and ZnPc 6, which we designed to test how π-extended anchoring groups and metalation modulate interfacial charge transfer (iCT) with LPE-TMDs. Clean isosbestic behavior and the emergence of an interfacial Q-band at ∼720 nm as seen in steady-state titrations with LPE-TMDs, namely s-WS2 and s-MoS2, underline strong ground-state electronic coupling. In the excited state, femtosecond transient absorption spectroscopy corroborates ultrafast formation of interfacial charge-separated states (iCSS) with characteristic signatures in the short-wave infrared (SWIR) and multiphasic decay kinetics. The direction of iCSS depends on the alignment of the phthalocyanine orbitals with respect to the TMDs band structure. Pyrenylimidazolyl groups enhance immobilization onto s-TMD and foster spin-conversion between iCSS of singlet and triplet multiplicities. Responsible are the rigid phthalocanine-to-pyrenylimidazolyl linkage as well as the charge transfer transition from pyrene to the phthalocyanine core. Overall, these results establish how the molecular design impacts interfacial interactions and processes in phthalocyanine@s-TMD and provide key design rules for tailoring excitonic and electronic processes in mixed-dimensional optoelectronic systems.

We report an unprecedented reaction of a diketopyrrolopyrrole (DPP) with primary and secondary amines that results in the ring-opening of the core with loss of its fluorescence. The various characterization techniques used in this study, such as X-ray diffraction, NMR spectroscopy, mass spectrometry, and UV-vis analysis, warrant accurate identification of the structures of the newly synthesized compounds. DFT studies were also performed in order to understand the mechanism associated with this reaction.

In this study, a computer‐aided drug design (CADD) approach was developed for a focused chemical library of eight synthesized thiazolo[5,4‐ c ]isoquinoline (TzIQ) derivatives, including four neutral compounds and their corresponding cationic derivatives, all methylated at N4. Our CADD approach involved target prediction using Mondrian conformal prediction with the ChEMBL database, which contains data from 550 human protein targets with diverse bioactivity profiles. This analysis identified that TzIQ had a high probability of being active against the enzyme dihydrofolate reductase (DHFR). Moreover, molecular docking predictions against Staphylococcus aureus DHFR ( sa DHFR) and Escherichia coli DHFR ( ec DHFR) highlighted three promising TzIQ for each enzyme: 2 , 4 , and 8 for sa DHFR, and 4 , 7 , and 8 for ec DHFR. These compounds demonstrated significant ligand–protein energy scores and relevant binding affinities with the sa DHFR and ec DHFR pocket residues, respectively. The subsequent in vitro antibacterial evaluation against S. aureus and E. coli confirmed the docking predictions for derivative 8 in both bacteria. Additionally, derivatives 6 and 7 emerged as novel antibacterial compounds against S. aureus , with all hits exhibiting MIC values ≤100 µg/mL.

Diketopyrrolopyrroles (DPP) are a versatile group of dyes and pigments with a wide range of applications, namely in the biological field. In this paper, we report the synthesis and the photodynamic activity of new cationic DPP derivatives that effectively inactivate Gram-positive and Gram-negative bacteria. These new compounds were synthetized using an easy synthetic procedure to introduce one or two pyridin-4-ylsulfanyl units followed by cationization. The photodynamic effectiveness of these DPP derivatives against Pseudomonas aeruginosa [Gram-negative] and methicillin-resistant Staphylococcus aureus [Gram-positive] strains was studied. Their photodynamic activity was also studied in the presence of potassium iodide (KI). Overall, both neutral and cationic DPP derivatives were highly effective in inactivating S. aureus, while only the cationic compounds were efficient against P. aeruginosa. Our findings suggest that for S. aureus, the production of singlet oxygen and a non-symmetrical structure were key factors in the photodynamic inactivation (PDI) success, whereas, for P. aeruginosa, the presence and number of cationic charges played a more significant role. In all cases, the application of KI reduced both the treatment time and PS concentration required for effective photodynamic inactivation of the studied bacteria. The ability to tailor simple DPP derivatives into effective DPP-based PSs for the inactivation of multidrug-resistant pathogenic bacterial strains, and the synergistic impact produced by the addition of KI, opens new possibilities for focused antimicrobial therapy. Graphical abstract

An efficient protocol was developed for the microwave-mediated metallation of 5-(4-methoxycarbonylphenyl)-10,15,20-tris(pentafluorophenyl)porphyrin (P1) with bis(benzonitrile)platinum dichloride salt and subsequent 1,3-dipolar cycloaddition of the resulting PtP1 with an azomethine ylide to give two isomeric metallochlorins: PtC1 (main isomer) and PtC3. The methyl ester group of metalloporphyrin PtP1 and metallochlorin PtC1 was successfully hydrolysed in an alkaline medium to yield the corresponding derivatives PtP2 and PtC2 in moderate-to-good yields. As a proof of concept of the reactivity of the carboxy group in PtP2 and PtC2, these compounds were conjugated with a hydroxylated derivative of indomethacin, a known potent non-steroidal anti-inflammatory, obtaining the conjugates PtP2-Ind and PtC2-Ind. The obtained platinum(II) porphyrins and chlorins were characterized by UV-Vis, NMR spectroscopy and mass spectrometry. The structure of PtP1 was also confirmed by X-ray crystallography. Singlet oxygen generation studies were carried out, as well as theoretical calculations, which demonstrated that the prepared Pt(II) complexes can be considered potential photosensitizers for PDT.

Click chemistry to allow in vivo conjugation of a fluorophore porphyrin (Por)-tetrazine (Tz) with the human epidermal growth factor receptor 2 (HER2)-targeting trastuzumab conjugated with trans-cyclooctene (TCO) is described here. In vitro experiments confirmed successful click reactions between Por-Tz and trastuzumab-TCO and validated preserved trastuzumab immunoreactivity (no significant change in HER2 binding, p > 0.05). Positron emission tomography (PET) of [⁸⁹Zr]Zr-DFO-trastuzumab-TCO demonstrated 17.1 ± 2.9% injected dose per gram of tumor at 48 h postinjection. Optical imaging showed an ∼10-fold increase in the click group for Por-Tz when compared with Por-Tz alone. This preclinical data demonstrate a pretargeted approach for dual PET and optical imaging of HER2-expressing tumors.