Acidic NH Research Articles

Synthesis, X-ray structures, and anion binding properties of 1,8-disulfonamidocarbazole-di(thio)amide hybrid macrocycles

An easy-to-prepare 1,8-disulfonamidocarbazole-diamide hybrid macrocycle 1 and its thioamide analogue 2 were reported, along with their anion recognition properties as determined by UV–vis and 1H NMR spectroscopic titrations as well as single crystal X-ray diffraction analyses. The conversion of amides into thioamides in the macrocyclic structures generated notable effects on the anion-binding affinity and selectivity. For example, amide-bearing macrocycle 1 was found to bind H2PO4- over one order of magnitude more strongly than thioamide-containing macrocycle 2, despite having more acidic NH groups for the latter. Additionally, macrocycle 1 displayed the highest affinity for PhCOO- in DMSO (Ka >105 M-1 for the formed 1:1 complex) followed by H2PO4- and AcO- ions, whereas a different binding order AcO- > PhCOO- >> H2PO4- was observed for macrocycle 2. More importantly, the single crystal X-ray diffraction analysis clearly revealed that macrocycle 1 indeed formed a 1:1 complex with PhCOO- ion in the solid state.

Dicationic salt of β-alkyl substituted sapphyrin-type porphyrinoid: Acid-basic properties, thermal stability and quantum-chemical calculations

The UV-Vis spectra of the dicationic salt of 2,3,7,13,17,18,18,22,23-octamethyl-8,12-diethylsapphyrin {H5β-Me8Et2Sap[Formula: see text](Cl[Formula: see text]} in solutions with different polarity and acid-basic properties have been investigated. The tautomeric and acid-base equilibria of H5β-Me8Et2Sap[Formula: see text](Cl[Formula: see text] in the presence of organic bases have been examined by spectrophotometric titration. It was demonstrated that an addition of small amounts of 1,8-diazabicyclo[5.4.0]undecene (DBU) and tetramethylammonium hydroxide (Me4NOH) dissolved in methylene chloride (DCM) and MeOH, respectively results in a stepwise detachment of two protons from the basic nitrogen atoms of the macrocycle, with no anionic forms of sapphyrin being registered. The results obtained were supported using quantum-chemical calculations (DFT, B3LYP, cc-pVDZ including NBO analysis). The interactions of 2,3,7,13,17,18,18,22,23-octamethyl-8,12-diethylsapphyrin (H3β-Me8Et2Sap) with a series of compounds of different acidity and basicity were studied and the formation of very weak hydrogen bond of H3β-Me8Et2Sap as NH-acid with N,N-dimethylformamide (DMF) molecule with the value of the interaction energy (E[Formula: see text] equal -16.40 kJ/mol was revealed. The low acidity of bonds NH in the sapphyrin molecule was confirmed on the base of thermogravimetric data obtained for the solid samples of H5β-Me8Et2Sap[Formula: see text](Cl[Formula: see text] evaporated from DMF and DCM concentrated solutions.

New Potent Sulfonamide-Based Inhibitors of S. aureus Biotin Protein Ligase.

The key regulatory metabolic enzyme, biotin protein ligase (BPL), is an attractive target for the development of novel antibiotics against multi-drug-resistant bacteria, such as Staphylococcus aureus. Here we report the synthesis and assay of a new series of inhibitors (6-9) against S. aureus BPL (SaBPL), where a component sulfonamide linker was used to mimic the acyl-phosphate group of the natural intermediate biotinyl-5'-AMP (1). A pivotal correlation between the acidity of the central NH of the sulfonamide linker of 6-9 and in vitro inhibitory activity against SaBPL was observed. Specifically, sulfonylcarbamate 8, with its highly acidic sulfonyl central NH, as evaluated by 1H NMR spectroscopy, showed exceptional potency (K i = 10.3 ± 3.8 nM). Furthermore, three inhibitors demonstrated minimum inhibitory concentrations of 16-32 μg/mL against clinical methicillin-resistant S. aureus (MRSA) strains.

Synthesis of 1,4‐Disubstituted and 1‐Substituted β‐Carbolines via 3‐Substituted 2‐Acylindoles

Abstractβ‐Carbolines represent a large class of bioactive natural products, whereby most of these alkaloids bear residues at C1, and occasionally at C3, and only limited examples of 1,4‐disubstituted β‐carbolines are known. In this project we worked out a novel approach to 1,4‐disubstituted β‐carbolines and performed a comprehensive analysis of the scope and limitations of this methodology. The 1,4‐disubstituted β‐carbolines were synthesized via 3‐substituted 2‐acylindoles, for which effective synthesis procedures were developed. Our studies revealed that a broad range of target compounds with electron‐withdrawing substituents at C4 are accessible. Limitations of this method arose from competing CH and NH acidities of precursors. Nevertheless, the work described herein provides a unique approach to highly substituted β‐carbolines. In addition, intermediates from this route opened a novel approach to 1‐substituted β‐carbolines utilizing a chemoselective Mo(CO)6‐catalyzed amide reduction with tetramethyldisiloxane.

Carboxylate-Catalyzed C-Silylation of Terminal Alkynes.

A carboxylate-catalyzed, metal-free C-silylation protocol for terminal alkynes is reported using a quaternary ammonium pivalate as the catalyst and commercially available N,O-bis(silyl)acetamides as silylating agents. The reaction proceeds under mild conditions, tolerates a range of functionalities, and enables concomitant O- or N-silylation of acidic OH or NH groups. A Hammett ρ value of +1.4 ± 0.1 obtained for para-substituted 2-arylalkynes is consistent with the proposed catalytic cycle involving a turnover-determining deprotonation step.

Urocanic acid as a novel scaffold for next-gen nature-inspired sunscreens: I. electronic laser spectroscopy under isolated conditions.

Urocanic acid is a naturally occurring UV-A and UV-B absorbing compound found in the skin. Its use in artificial sunscreens has been abandoned because of health risks associated with the cis isomer. Here we report laser spectroscopic studies on urocanic acid and various substituted derivatives under supersonically cooled conditions. We find that the spectroscopy and excited-state dynamics of urocanic acid are dominantly determined by the nearly degenerate 1nπ* and 1ππ* electronically excited states. These properties are only affected to a minor extent by esterification of the carboxylic acid group or NH alkylation of the N3H tautomer. Tautomerization, on the other hand, has a much more profound influence and leads-from a photoprotective point of view-to more favorable excited-state dynamics. The approach presented here paves the way to tailoring the photoactive properties of urocanic acid for specific applications amongst which their use as safe UV filters.

Makromolekulare Hydrazon Hauptkettenphotoschalter

AbstractHydrazone – bestehend aus einer dynamischen Iminbindung und einem sauren NH‐Proton – haben sich in letzter Zeit aufgrund ihrer Fähigkeit zur Bildung thermisch bistabiler (Z) bzw. (E) Isomere als vielseitige Potoschalter erwiesen. In diesem Artikel stellen wir zwei lichtsensitive Homopolymere vor, die strukturell unterschiedliche Hydrazone als sich wiederholende Einheiten in der Hauptkette enthalten und durch „Kopf‐Schwanz“‐Polymerisation mittels azyklischer Dien‐METathese (ADMET) synthetisiert wurden. Der Hauptunterschied der beiden Polymere liegt dabei im Design des Hydrazon‐Photoschalters, insbesondere in der Lage des aliphatischen Arms, der den Rotor mit dem aliphatischen Polymerrückgrat verbindet. Es zeigt sich, dass sich das hydrodynamische Volumen der Polymere in verdünnter Lösung während der Photoisomerisierung (λ=410 nm) in entgegengesetzter Weise ändert. Darüber hinaus zeigt sich nach der Photoisomerisierung eine Veränderung der Glasübergangs‐temperatur (Tg) um fast 10 °C bei beiden Polymeren, unabhängig vom Design des jeweiligen Hydrazon‐Monomers. Die hier vorgestellte Designstrategie erlaubt es, makromolekulare Eigenschaften durch Strukturänderungen photochemisch zu kontrollieren.

Main-chain Macromolecular Hydrazone Photoswitches.

Hydrazones-consisting of a dynamic imine bond and an acidic NH proton-have recently emerged as versatile photoswitches underpinned by their ability to form thermally bistable isomers, (Z) and (E), respectively. Herein, we introduce two photoresponsive homopolymers containing structurally different hydrazones as main-chain repeating units, synthesized via head-to-tail Acyclic Diene METathesis (ADMET) polymerization. Their key difference lies in the hydrazone design, specifically the location of the aliphatic arm connecting the rotor of the hydrazone photoswitch to the aliphatic polymer backbone. Critically, we demonstrate that their main photoresponsive property, i.e., their hydrodynamic volume, changes in opposite directions upon photoisomerization (λ=410 nm) in dilute solution. Further, the polymers-independent of the design of the individual hydrazone monomer-feature a photoswitchable glass transition temperature (Tg ) by close to 10 °C. The herein established design strategy allows to photochemically manipulate macromolecular properties by simple structural changes.

Evaluating diethanolammonium chloride as liquid solvent for gas separation from experiments and theoretical calculations

AbstractThis study explored diethanolammonium chloride ([DEA]Cl) as a potential ionic liquid from low‐cost and commercial ones for gas separation. There are three kinds of functional sites in [DEA]Cl: acidic NH2+, hydrogen‐bond OH, and nucleophilic Cl−. The separation of NH3/N2/H2, SO2/CO2/N2, and H2S/CO2/CH4 was considered, because the three mixtures are extensively involved in many industrial processes. The experimental results demonstrated that [DEA]Cl exhibited excellent ability to separate the mixture of NH3/N2/H2. The [DEA]Cl also exhibited the proper capacity to separate SO2/CO2/N2, but the capacity of [DEA]Cl for the separation of H2S/CO2/CH4 was inferior. The theoretical calculations revealed that NH2+ and OH worked synergistically to contribute to the ability of [DEA]Cl for excellent separation of NH3 from NH3/N2/H2, with Cl− contributing to the proper separation of SO2 from SO2/CO2/N2. This study provides experimental and theoretical basis for the industrial application of [DEA]Cl in the area of gas separation.

Squaramide-Based Heteroditopic [2]Rotaxanes for Sodium Halide Ion-Pair Recognition.

A series of squaramide-based heteroditopic [2]rotaxanes consisting of isophthalamide macrocycle and squaramide axle components are synthesized using an alkali metal cation template-directed stoppering methodology. This work highlights the unprecedented sodium cation template coordination of the Lewis basic squaramide carbonyls for interlocked structure synthesis. Extensive quantitative 1 H NMR spectroscopic anion and ion-pair recognition studies reveal the [2]rotaxane hosts are capable of cooperative sodium halide ion-pair mechanical bond axle-macrocycle component recognition, eliciting up to 20-fold enhancements in binding strengths for bromide and iodide, wherein the Lewis basic carbonyls and Lewis acidic NH hydrogen bond donors of the squaramide axle motif operate as cation and anion receptive sites simultaneously in an ambidentate fashion. Notably, varying the length and nature of the polyether cation binding unit of the macrocycle component dramatically influences the ion-pair binding affinities of the [2]rotaxanes, even overcoming direct contact NaCl ion-pair binding modes in polar organic solvents. Furthermore, the cooperative ion-pair binding properties of the squaramide-based heteroditopic [2]rotaxanes are exploited to successfully extract solid sodium halide salts into organic media.

Hydrogenation of Carboxylic Esters Catalyzed by Phosphine-Free Bis-N-heterocyclic Carbene Manganese Complexes

As an earth-abundant transition metal, manganese is now recognized as a good candidate for the development of catalysts for reduction-type reactions. It is often associated with a noninnocent tridentate ligand, featuring an acidic NH moiety. We report here that a simple bidentate and phosphine-free bis-N-heterocyclic ligand associated with manganese in the complex [Mn(bis-NHCMes)(CO)3Br] could catalyze the hydrogenation of carboxylic esters in the presence of KBHEt3 as an activator at 100–120 °C under 50 bar of H2 at 1 mol % catalyst loading in 2-Me-THF.

Brønsted Base Prompted sp3 C-H Latent Nucleophiles to Access α-Branched Amines Bearing β-Carbonyl by Cleaving Amide and Ester Bonds.

α-Branched amines are key motifs that exist in a plethora of natural products and pharmaceuticals. Herein we disclose the first convergent synthesis of α-branched amines bearing β-carbonyl in isoindolinones by employing unactivated tertiary amides and unactivated alkyl esters as benign electrophile sources. The reaction proceeds by the direct aroylation of a C(sp3)-H carbon adjacent to the nitrogen atom in core isoindolinones. Several amides and esters were screened to choose the potential acyl source for the substrate scope. The reaction is carried out with a repertoire of substrates under mild conditions and shows high functional group compatibility. Remarkably the reaction is amenable to organometallic ferrocenyl ester and indole methyl esters bearing an acidic NH moiety. Strikingly no trace of amidation product 8 is observed. In particular α-branched amines bearing β-carbonyl synthesized from indole methyl esters are considered important targets, as both motifs are prevalent in many drugs. This protocol is scalable, and products obtained from indole methyl esters show strong solid-state emission properties which are complementary with DFT calculations.

Microhydration of the Pyrrole Cation (Py+) Revealed by IR Spectroscopy: Ionization-Induced Rearrangement of the Hydrogen-Bonded Network of Py+(H2O)2

Microhydration of heterocyclic aromatic molecules can be an appropriate fundamental model to shed light on intermolecular interactions and functions of macromolecules and biomolecules. We characterize herein the microhydration process of the pyrrole cation (Py+) by infrared photodissociation (IRPD) spectroscopy and dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ). Analysis of IRPD spectra of mass-selected Py+(H2O)2 and its cold Ar-tagged cluster in the NH and OH stretch range combined with geometric parameters of intermolecular structures, binding energies, and natural atomic charge distribution provides a clear picture of the growth of the hydration shell and cooperativity effects. Py+(H2O)2 is formed by stepwise hydration of the acidic NH group of Py+ by a hydrogen-bonded (H2O)2 chain with NH···OH···OH configuration. In this linear H-bonded hydration chain, strong cooperativity, mainly arising from the positive charge, strengthens both the NH···O and OH···O H-bonds with respect to those of Py+H2O and (H2O)2, respectively. The linear chain structure of the Py+(H2O)2 cation is discussed in terms of the ionization-induced rearrangement of the hydration shell of the neutral Py(H2O)2 global minimum characterized by the so-called "σ-π bridge structure" featuring a cyclic NH···OH···OH···π H-bonded network. Emission of the π electron from Py by ionization generates a repulsive interaction between the positive π site of Py+ and the π-bonded OH hydrogen of (H2O)2, thereby breaking this OH···π hydrogen bond and driving the hydration structure toward the linear chain motif of the global minimum on the cation potential.

Photochemical study and vibrational spectra of propiolamide isolated in low-temperature Ar, Xe, and N2 matrices

Propiolamide (HCCCONH2, PA) has been isolated in low-temperature matrices (Ar, Xe, and N2) and studied by matrix isolation infrared (IR) spectroscopy and quantum chemical calculations undertaken at the DFT(B3LYP)/6-311++G(d,p) level of theory. In situ broadband UV light (λ > 235 nm) irradiation of matrix-isolated PA led to the observation of new bands ascribed to different photoproducts resulting from three distinct photoreaction pathways: (i) tautomerization to propiolimidic acid (HCCC(OH)NH), (ii) CC bond cleavage, with formation of acetylene (HCCH) and isocyanic acid (HNCO), and (iii) decarbonylation, leading to generation of ethynamine (HCCNH2). Pathways (i) and (ii) were observed in all matrices, while (iii) was only observed in the matrices of the rare gases. Observation of characteristic bands due to the different photoproducts has been established, and the assignment of the IR spectra for all the species was carried out. As a whole, the detailed structural, vibrational, and photochemical data reported in this article appear relevant to the rational practical use of PA in its multiple application areas (in particular in the pharmaceutical and materials sciences domains) as well as for its analytical determination, including its search in the interstellar space.

Opening of the Diamondoid Cage upon Ionization Probed by Infrared Spectra of the Amantadine Cation Solvated by Ar, N2 , and H2 O.

Radical cations of diamondoids, a fundamental class of very stable cyclic hydrocarbon molecules, play an important role in their functionalization reactions and the chemistry of the interstellar medium. Herein, we characterize the structure, energy, and intermolecular interaction of clusters of the amantadine radical cation (Ama+, 1‐aminoadamantane) with solvent molecules of different interaction strength by infrared photodissociation (IRPD) spectroscopy of mass‐selected Ama+L n clusters, with L=Ar (n≤3) and L=N2 and H2O (n=1), and dispersion‐corrected density functional theory calculations (B3LYP−D3/cc‐pVTZ). Three isomers of Ama+ generated by electron ionization are identified by the vibrational properties of their rather different NH2 groups. The ligands bind preferentially to the acidic NH2 protons, and the strength of the NH…L ionic H‐bonds are probed by the solvation‐induced red‐shifts in the NH stretch modes. The three Ama+ isomers include the most abundant canonical cage isomer (I) produced by vertical ionization, which is separated by appreciable barriers from two bicyclic distonic iminium ions obtained from cage‐opening (primary radical II) and subsequent 1,2 H‐shift (tertiary radical III), the latter of which is the global minimum on the Ama+ potential energy surface. The effect of solvation on the energetics of the potential energy profile revealed by the calculations is consistent with the observed relative abundance of the three isomers. Comparison to the adamantane cation indicates that substitution of H by the electron‐donating NH2 group substantially lowers the barriers for the isomerization reaction.

Anion and Temperature Responsive Molecular Switches Based on Trimetallic Complexes of Ru(II) and Os(II) That Demonstrate Advanced Boolean and Fuzzy Logic Functions.

Anion- and temperature-induced alteration of the photoredox behaviors of our recently reported trimetallic complexes was carried out to fabricate potential molecular switches. The triads [(phen)2Ru(d-HIm-t)M(t-HIm-d)Ru(phen)2]6+ (phen = 1,10-phenanthroline, d-HIm-t = heterotopic bipyridine-terpyridne type bridging ligand, and M = RuII and OsII) possess two acidic imidazole NH protons that upon interaction with anions give rise to considerable changes in their photophysical and electrochemical behaviors. Red-shifts of the absorption and emission maximum and a decrease in the M3+/M2+ potential occur when the triads are treated with basic anions. In fact, the triads can function as triple-channel sensors for F-, AcO-, CN-, OH-, and H2PO4- in acetonitrile and as selective probes for CN- and SCN- in water. The equilibrium constants for the receptor-anion interaction are on the order of 106 M-1, while the limit of detection was on the order of 10-9 M. Temperature plays a key role in the luminescence properties of the triads by adjusting the energy barrier between the emitting triplet metal-to-ligand charge transfer and non-emitting triplet metal-centered levels. A decrease in temperature leads to increases in the emission intensity and lifetime of the triads displaying the "on state", whereas an increase in temperature leads to a decrease in their emission characteristics and thus indicates the "off state" and that the process is fully reversible. In essence, the triads could function as potential switches on the basis of the reversible change in their spectral and redox behaviors under the influence of anion, acid, and temperature. The most important outcome of this study is mimicking several advanced Boolean and fuzzy logic functions by utilizing the spectral response of the triads upon the action of said external stimuli.

Prussian blue based impedimetric urea biosensor

• Prussian blue (PB) based impedimetric urea biosensor was designed. • FTO was modified by Prussian blue and immobilized urease (glass/FTO/PB/urease biosensor). • Sensitivity of the glass/FTO/PB/urease biosensor is 2.55 Ω cm 2 mM −1 . • The glass/FTO/PB/urease biosensor exhibits linear range from 0.1 mM to 5.4 mM. • Acidic conditions improve PB stabilisation in ammonium ion containing medium. In this research an impedimetric urea biosensor was formed by modifying a fluorine doped tin oxide coated glass slide (glass/FTO) with a layer of PB (glass/FTO/PB), which was further stabilized in ammonium ion-containing medium, and immobilizing urease (glass/FTO/PB/urease) with vapor of glutaric aldehyde. Fast Fourier transform electrochemical impedance spectroscopy (FFT-EIS) investigation of the glass/FTO/PB/urease-based biosensor in urea-containing buffer solution indicated that the glass/FTO/PB/urease-based biosensor exhibits good sensitivity to urea (2.55 Ω cm 2 mM −1 ) and a range of linearly detectable concentrations of urea from 0.1 mM to 5.4 mM (R 2 = 0.992). To determine the optimal conditions of PB layer stabilisation, the influence of acidity of NH 4 Cl solution on the efficiency of cyclic voltammetry-based stabilization of PB layer was investigated in this research as well.

Electrochemistry of Quinones with Respect to their Role in Biomedical Chemistry.

Quinones are ubiquitous in nature and form one of the largest class of antitumor agents approved for clinical use. They are known to be efficient in inhibiting cancer cells growth. Under physiological conditions they can undergo non-enzymatic one-electron reduction to give the moderately toxic species of semiquinone radical-anion. Thus, electrochemical study of quinones might provide a basic knowledge on semi-quinone radicals formation in both in vivo and in vitro under different media. Several processes are outlined briefly and discussed in the present article. Previously we investigated the electrochemical and spectral properties of ω-N-quinonyl amino acids. Such quinone-bearing peptides are known to be cytotoxic and of potential clinical significance. We were able to prove that the ω-amino quinonyl compounds are very effective in producing stable semiquinone radicals. Moreover, a direct relation was found between the first reduction potentials of the quinonyl moiety and their reactivity towards the ω-amino acids. In order to increase our knowledge of such amino quinonyl compounds and enlarge the arsenal of such cytotoxic compounds, a series of N,N-diquinonyl amines (1-6) bearing an internal proton (stems from the NH moiety) were synthesized. Their electron-transfer capabilities were probed by cyclic voltammetry measurements, in dichloromethane. It was found that the acidic NH group linking the two quinonyl moieties undergoes an initial electrochemical reduction step and generates a nitride anion. This step is followed by further reductions to yield quasi-stable semiquinone radicals and polyanions, Since these acidic diquinones (1-6) serve also as a source of internal proton donors even in non-polar medium, they might cause protonation of basic radical-anions and polyanion intermediates during the various electrochemical stages. The processes are demonstrated and discussed by analyzing different mechanistic schemes. The successful generation of relatively stable semiquinone radicals is a prerequisite for the manifestation of site directed antitumor activity by these bis-quinonyl amino derivatives. Based on the values of their redox potentials some of them could be promising candidates for clinical development.

On the NH and CH acidities of toluidine isomers: theoretical description and practical consequences for the synthesis of certain aniline dyes

AbstractFor the toluidine isomers, amino group acidity represents a characteristic feature of these compounds in their electric neutral state. As demonstrated by theoretical calculations based on the quantum chemistry composite G4 method and density functional theory, the CH acidity of the methyl group is hidden under NH acidity. The transformation of toluidines into their mono‐ and bi‐oxidised states significantly increases the acidity of the methyl group. This study indicates that the presence or absence of these deprotonated species in reaction mixtures will determine the CN or CC coupling toluidine products. In agreement with published synthetic approaches for aniline dyes, such as mauveine and fuchsine, the results obtained explain the alternative reaction pathways occurring during the oxidation of toluidine isomers.

Design and Syntheses of New Antibiotics Inspired by Nature's Quest for Iron in an Oxidative Climate.

This Account describes fundamental chemistry that promoted the discovery of new antibiotics. Specifically, the NH acidity of simple hydroxamic acid derivatives facilitated the syntheses of novel β-lactams (oxamazins and monobactams), siderophore mimics that limit bacterial iron uptake and bacterially targeted sideromycins (siderophore-antibiotic conjugates). The development of resistance to our current limited set of antibiotic scaffolds has created a dire medical situation. As recently stated, "if you weren't taking antibiotic resistance seriously before, now would be a good time to start." A project commissioned by the British government (https://amr-review.org/) has released estimates of the near-future global toll of antibiotic resistance that are jaw-dropping in their seriousness and scale: 10 million deaths per year and at least $100 trillion in sacrificed gross national product. The 2020 COVID pandemic confirmed that infectious disease problems are no longer localized but worldwide. Many classical antibiotics, especially β-lactams, previously provided economical cures, but the evolution of antibiotic destructive enzymes (i.e., β-lactamases), efflux pumps, and bacterial cell wall permeability barriers has made many types of bacteria, especially Gram-negative strains, resistant. Still, and in contrast to other therapies, the public expectation is that any new antibiotic must be inexpensive. This creates market limitations that have caused most major pharmaceutical companies to abandon antibiotic research. Much needs to be done to address this significant problem.The critical need for bacteria to sequester essential iron provides an Achilles' heel for new antibiotic development. Although ferric iron is extremely insoluble, bacteria need micromolar intracellular concentrations for growth and virulence. To this end, they biosynthesize siderophores (Gr. iron bearer) and excrete them into their environment, where they bind iron with high affinity. The iron complexes are recognized by specific outer-membrane transporters, and once actively internalized, the iron is released for essential processes. To conserve biosynthetic energy, some bacteria recognize and utilize siderophores made by competing strains. As a counter-revolution in the never-ending fight for survival, bacteria have also evolved sideromycins, which are siderophores conjugated to warheads that are lethal to rogue bacteria. While none are now used therapeutically, natural sideromycins called albomycins have been used clinically, and others have been shown to be well tolerated and active in animal infection models. Herein we describe practical methods to synthesize new antibiotics and artificial sideromycins with the generalized structure shown above (siderophore-linker drug). Utilizing the molecular-recognition-based siderophore/sideromycin bacterial assimilation processes, it is possible to design both broad spectrum and exquisitely narrow spectrum (targeted) sideromycins and even repurpose older or more classical antibiotics. Relevant microbiological assays, in vivo animal infection studies, and the recent FDA approval of cefiderocol demonstrate their effectiveness.