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The airborne pathogen Mycobacterium tuberculosis is responsible for a present major public health problem worsened by the emergence of drug resistance. M. tuberculosis has acquired and developed streptomycin (STR) resistance mechanisms that have been maintained and transmitted in the population over the last decades. Indeed, STR resistant mutations are frequently identified across the main M. tuberculosis lineages that cause tuberculosis outbreaks worldwide. The spread of STR resistance is likely related to the low impact of the most frequent underlying mutations on the fitness of the bacteria. The withdrawal of STR from the first-line treatment of tuberculosis potentially lowered the importance of studying STR resistance. However, the prevalence of STR resistance remains very high, could be underestimated by current genotypic methods, and was found in outbreaks of multi-drug (MDR) and extensively drug (XDR) strains in different geographic regions. Therefore, the contribution of STR resistance to the problem of tuberculosis drug resistance should not be neglected. Here, we review the impact of STR resistance and detail well-known and novel candidate STR resistance mechanisms, genes, and mutations. In addition, we aim to provide insights into the possible role of STR resistance in the development of multi-drug resistant tuberculosis., This research was funded by NORTE-01-0145- FEDER-000039, NORTE-01-0145-FEDER000013, and NORTE-01-0145-FEDER-00002, supported by Norte Portugal Regional Operational Program (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). It was also funded through the Foundation for Science and Technology (FCT)—project FCT IF/00474/2014, UIDB/50026/2020, and UIDP/50026/2020. DR was funded by FCT Ph.D. scholarships (grant number SFRH/BD/135422/2017). DR was partially funded by the PGCD—Graduate Program Science for Development. MS is supported by FCT through the Estimulo ao Emprego Científico.

We report a novel synthetic approach, with good yields, for the synthesis of selective dimethylamine-substituted phthalonitriles (1-3) in the presence of triethyl phosphite and dimethylformamide at 160 degrees C. The peripherally modified dimethylamine substituted Zn(II) phthalocyanines (ZnPc1-3) with varied numbers and positions of dimethylamine groups were prepared for a systematic investigation of the effect of the substituents on their electronic and spectroscopic properties. Compounds show strong aggregation behaviour in methanol and this behaviour decreases with the increase of the alkyl chain length of the alcohol solvents (i.e., from methanol to octanol). The fluorescence quantum yields of ZnPc1-3 showed an excellent correlation with the extent of the molecular aggregation. The versatility of the ZnPc1-5 compounds possessing both electron donating and electron withdrawing substituents at their periphery is investigated towards the detection of nitroaromatic compounds (NACs) in solution and in the vapour phase. It was found that ZnPc1-5 exhibit high selectivity towards trinitrophenol (TNP). A good linearity of fluorescence detection using ZnPc3 as the fluorescent probe was observed in the concentration range of 50 x 10(-6) to 450 x 10(-6) M in chloroform, with a detection limit (LOD) of 11 +/- 2 ppm. Stern-Volmer (SV) and DFT studies reveal that the fluorescence quenching behaviour occurs through photo-induced electron transfer from the excited state of ZnPcs to TNP with static quenching behaviour occurring in a predominant fashion. The formation of a porous morphology of ZnPc3 thin films promotes high selectivity and accessibility to TNP vapours (7.7 x 10(-3) ppb).