Exploring the Explosive Potential: Synthesis and Characterization of Ring-Fused Oxadiazolo[3,4-b]pyrazine 1-Oxide Polymorphs with Balanced Energetic Properties.

A novel fused-ring compound, 5-azido-6-oxo-6,7-dihydro-[1,2,5]oxadiazolo[3,4-b]pyrazine 1-oxide (3a), was synthesized for the first time with simple two-step process and characterized using various spectroscopic techniques such NMR, IR, EA and HRMS. Two polymorphs (α-3a and ß-3a) identified by SCXRD differ in crystal packing and noncovalent interactions, demonstrating high density, substantial heat of formation, and superior detonation properties with reduced mechanical sensitivity compared to TNT, TATB, and close to RDX, suggesting their potential as environmentally friendly high energy density materials.

Elevating the energetic capabilities of metal coordination compounds by incorporating nitrate anions.

In the realm of energetic materials research, there has been notable interest in energetic coordination compounds (ECCs) owing to their remarkable thermal stability and resistance to mechanical stimuli. This study successfully demonstrated the synthesis of an azole-based C-C bonded ECC1 under ambient conditions. A comprehensive characterization study, employing techniques such as IR, TGA-DSC, NMR and single-crystal X-ray diffraction analysis, was conducted. The bulk compound was investigated by PXRD analysis. In-depth exploration of its physicochemical and energetic performance revealed good detonation properties such as a detonation velocity (VOD) of 8553 m s-1 and a detonation pressure (DP) of 36.2 GPa, which surpass those of heat resistant explosives HNS and TATB. Due to its remarkable high melting and onset decomposition temperature (278/379 °C), it also outperforms the benchmark explosive HMX (279 °C) and the heat-resistant explosive HNS (318 °C) and shows a high impact sensitivity (IS) of 20 J and friction sensitivity (FS) of 360 N. The study also employed Hirshfeld surface and 2D fingerprint analysis to elucidate the close contact of atoms within the molecules. The combination of high detonation properties, thermal stability, and low sensitivity makes the synthesized ECC1 intriguing for further investigations and suggests its potential applications as a safe and high-energy-dense material.

Single Step Synthesis of gem-Dinitro Methyl-1,2,4-triazole and Its Hydroxylamine Salt: An Alternative to the FOX-7 and Other Benchmark Explosives.

gem-Dinitro methyl based high-energy-density material 5-(dinitromethylene)-4,5-dihydro-1H-1,2,4-triazole (2) and its hydroxylamine salt (4) were synthesized for the first time in a single step and characterized. Further, the structure of 2 was confirmed by single-crystal X-ray diffraction (SCXRD) studies. Interestengly, both the compounds show excellent density (> 1.83 g cm-3), detonation velocity (> 8700 m s-1), pressure (> 30 GPa) and are insensitive toward mechanical stimuli such as impact and friction sensitivity. Considering their synthetic fesibility and balanced energetic performance, compounds 2 and 4 show future prospects as potential next-generation energetic materials for the replacenent of many presently used benchmark high energy density materials such as RDX, FOX-7 and highly insensitive H-FOX.

Elaborating NH-Bridged Nitrogen-Rich Energetic Materials via Base-Mediated Dimroth Rearrangement: Synthesis, Characterization, and Performance Study.

The pursuit of heat-resistant energetic materials featuring high thermostability and energy has gained keen interest in recent years owing to their use in coal mining and aerospace domains. In this study, we synthesized 4-((4,6-diamino-1,3,5-triazin-2-yl) amino)-1H-1,2,3-triazole-5-carbonitrile (6) and its perchlorate and nitrate energetic salts (6a and 6b) by incorporating amino bridging (-NH-) using the Dimroth rearrangement (DR) from inexpensive starting materials as a heat-resistant energetic materials. All of the compounds were thoroughly characterized by infrared (IR), NMR, elemental analysis (EA), high-resolution mass spectrometry (HRMS), and thermogravimetric analysis-differential scanning calorimetry (TGA-DSC) studies. Compounds 6a and 6b showed good densities (1.81 and 1.80 g cm-3), detonation performance (VOD = 7505 and 8257 m s-1, DP = 23.47 and 24.41 GPa), insensitivity to mechanical stimuli (IS = 40 J and FS = >360 N), and excellent thermal stability (Td = 307 and 334 °C), surpassing presently used heat-resistant explosive HNS (318 °C). The molecular electrostatic potentials and noncovalent interactions were pursued to understand possible interaction sites and structure-directing interactions in these salts. Their facile synthetic approach, good energetic performance, and outstanding thermal stability indicate that they are the ideal combination for replacing current benchmark heat-resistant explosive HNS. Additionally, this study highlights the use of classical DR for making new energetic materials with fine-tuned properties.

Solvent Free Potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate 3D EMOF as Thermally Stable Energetic Material.

Heat-resistant explosives play a vital role in indispensable applications. For this, we have synthesized a novel, three-dimensional, solvent-free energetic metal-organic framework (EMOF) potassium 3,5-dinitro-6-oxo-1,6-dihydropyrazin-2-olate (KDNODP) straightforwardly. The synthesized EMOF was characterized through IR, NMR spectroscopy, elemental analysis, and differential scanning calorimetry studies. Furthermore, single-crystal X-ray diffraction provided a complete description of KDNODP. It exhibits a three-dimensional EMOF structure with remarkably balanced properties such as high density (2.11 g cm-3), excellent thermal stability (291 °C), good detonation performance (8127 m s-1 and 26.94 GPa) and low mechanical sensitivity (IS=35 J; FS=360 N) than the commonly used heat-resistant explosives HNS (density=1.74 g cm-3; VOD=7164 m s-1, DP=21.65 GPa, IS=5 J) as well as the similar reported energetic potassium MOFs. To gain insights into the packing and intermolecular interactions, the Hirshfeld surface and a 2D fingerprint analysis were examined. Additionally, scanning electron microscopy was used to investigate the particle size and morphological characteristics of KDNODP. These outcomes highlight a successful method for creating 3D EMOF based on a six-membered heterocycle as a potential heat-resistant energetic material.

Highly Dense N-N-Bridged Dinitramino Bistriazole-Based 3D Metal-Organic Frameworks with Balanced Outstanding Energetic Performance.

Due to the inherent conflict between energy and safety, the construction of energetic materials or energetic metal-organic frameworks (E-MOFs) with balanced thermal stability, sensitivity, and high detonation performance is challenging for chemists worldwide. In this regard, in recent times self-assembly of energetic ligands (high nitrogen- and oxygen-containing small molecules) with alkali metals were probed as a promising strategy to build high-energy materials with excellent density, insensitivity, stability, and detonation performance. Herein, based on the nitrogen-rich N,N'-([4,4'-bi(1,2,4-triazole)]-3,3'-dial)dinitramide (H2BDNBT) energetic ligand, two new environmentally benign E-MOFs including potassium [K2BDNBT]n (K-MOF) and sodium [Na2BDNBT]n (Na-MOF) have been introduced and characterized by NMR, IR, TGA-DSC, ICP-MS, PXRD, elemental analyses, and SCXRD. Interestingly, Na-MOF and K-MOF demonstrate solvent-free 3D dense frameworks having crystal densities of 2.16 and 2.14 g cm-3, respectively. Both the E-MOFs show high detonation velocity (VOD) of 8557-9724 m/s, detonation pressure (DP) of 30.41-36.97 GPa, positive heat of formation of 122.52-242.25 kJ mol-1, and insensitivity to mechanical stimuli such as impact and friction (IS = 30-40 J, FS > 360 N). Among them, Na-MOF has a detonation velocity (9724 m/s) superior to that of conventional explosives. Additionally, both the E-MOFs are highly heat-resistant, having higher decomposition (319 °C for K-MOF and 293 °C for Na-MOF) than the traditional explosives RDX (210 °C), HMX (279 °C), and CL-20 (221 °C). This stability is ascribed to the extensive structure and strong covalent interactions between BDNBT2- and K(I)/Na(I) ions. To the best of our knowledge, for the first time, we report dinitramino-based E-MOFs as highly stable secondary explosives, and Na-MOF may serve as a promising next-generation high-energy-density material for the replacement of presently used secondary thermally stable energetic materials such as RDX, HNS, HMX, and CL-20.

Bistriazolotriazole-tetramine: commendable energetic moiety and cation.

CONTEXT: Various 7H,7'H-[6,6'-bi[1,2,4]triazolo[4,3-b][1,2,4]triazole]-3,3',7,7'-tetramine (A) based nitrogen-rich energetic salts were designed and their properties explored. All energetic salts possess relatively high nitrogen content (> 48%), positive heats of formation (> 429 kJ/mol) and stability owing to a significant contribution from fused backbone. The cationic component shows a very high heat of formation (2516 kJ/mol); therefore, it is highly suitable for enthalpy enhancement in new energetic salts. The cation was paired with the energetic anions nitrate (NO3-), perchlorate (ClO4-), dinitromethanide (CH(NO2)2-), trinitromethanide (C(NO2)3-), nitroamide (NHNO2-), and dinitroamide (N(NO2)2-) to improve oxygen balance and detonation performance. Designed salts show moderate detonation velocities (7.9-8.7 km/s) and pressures (23.8 - 33.1 GPa). The distribution of frontier molecular orbitals, molecular electrostatic surface potentials, QTAIM topological properties, and noncovalent interactions of designed salts were simulated to understand the electronic structures, charge distribution in molecules, hydrogen bonding, and other nonbond interactions. The predicted safety factor (SF) and impact sensitivity (H50) of designed salts suggest their insensitivity to mechanical stimuli. This work explored the 7H,7'H-[6,6'-bi[1,2,4]triazolo[4,3-b][1,2,4]triazole]-3,3',7,7'-tetramine as a suitable cationic component which could be promising and serve exemplarily in energetic materials. METHODS: The optimization and energy calculations of all the designed compounds were carried out at the B3LYP/6-311 + + G(d,p) and M06-2X/def2-TZVPP levels, utilizing the Gaussian software package. The molecular surface electrostatic potential, quantum theory of atoms in molecules (QTAIM), reduced density gradient (RDG), and noncovalent interaction (NCI) analysis were performed by employing Multiwfn software. The EXPLO5 (v 7.01) thermochemical code and PILEM web application were used to predict the detonation properties.

Zwitterionic fused pyrazolo-triazole based high performing energetic materials.

A series of nitrogen-rich fused energetic materials were synthesized from commercially available inexpensive starting materials and fully characterized using 1H and 13C NMR, IR spectroscopy, elemental analysis, and DSC. The structure of zwitterionic compound 2 was supported by SCXRD data. Among all, 3 and 4 possess excellent detonation velocity (8956 and 9163 m s-1) and are insensitive towards friction (>360 N) and impact (10 J), having moderate to excellent thermal stability (171-262 °C). It is worth mentioning that the zwitterionic fused pyrazolo-triazole compound 2 and its energetic salts offer remarkable performance as new-generation thermally stable energetic materials.

Azo-Bridged Triazole Macrocycles: Computational Design, Energy Content, Performance, and Stability Assessment.

Oxadiazole and triazole are extensively investigated heterocyclic scaffolds in the development of energetic materials. New energetic molecules were designed by replacing 1,2,5-oxadiazole with 2H-1,2,3-triazole in the reported conjugated macrocyclic systems to assess the influence on the energetic properties and stability. In addition, nitro groups were introduced in triazole units (N-functionalization) to improve the energetic performance. Energetic properties, including heat of formation, oxygen balance, density, detonation pressure and velocity, and impact sensitivity, were estimated for these triazole-based macrocycles. The replacement of 1,2,5-oxadiazole with 2H-1,2,3-triazole and 2-nitro-1,2,3-triazole significantly enhances the energy content, detonation performance, and noncovalent interactions. The theoretically computed energetic properties of triazole-based macrocycles reveal high positive heats of formation (1507-2761 kJ/mol), oxygen balance (-88.8 to -22.8%), high densities (1.87-1.90 g/cm3), superior detonation velocities (8.41-9.52 km/s), pressures (26.64-40.55 GPa), acceptable impact sensitivity (27-40 cm), and safety factor (51-290). The overall energetic assessment highlights triazole-based macrocycles as a potential framework that will be useful for developing advanced energetic materials.

Synthesis of Advanced Pyrazole and N-N-Bridged Bistriazole-Based Secondary High-Energy Materials.

In this work, we have synthesized 3,5-dihydrazinyl-4-nitro-1H-pyrazole (2), 9-nitro-1H-pyrazolo[3,2-c:5,1-c']bis([1,2,4]triazole)-3,6-diamine (3), and N-N-bonded N,N'-{[4,4'-bi(1,2,4-triazole)]-3,3'-diyl}dinitramide (5) and its stable nitrogen-rich energetic salts in one and two steps in quantitative yields from commercially available inexpensive starting material 4,6-dichloro-5-nitropyrimidine (1). Along with characterization via nuclear magnetic resonance, infrared, differential scanning calorimetry, and elemental analysis, the structures of 2 and 4-8 were confirmed by single-crystal X-ray diffraction. Interestingly, 5-8 show excellent thermal stability (242, 221, 250, and 242 °C, respectively) compared to that of RDX (210 °C). Detonation velocities of 2, 4, 6, and 7 range from 8992 to 9069 m s-1, which are better than that of RDX (8878 m s-1) and close to that of HMX (9221 m s-1). All of these compounds are insensitive to impact (10-35 J) and friction (360 N) sensitivity. These excellent energetic performances, stabilities, and synthetic feasibilities make compounds 2, 4, 6, and 7 promising candidates as secondary explosives and potential replacements for the presently used benchmark explosives RDX and HMX.

Energetic coordination compounds: self-assembled from the nitrogen-rich energetic C-C bonded pyrazoles and triazoles.

In energetic materials research, energetic coordination compounds (ECCs) have received much attention due to their high thermal stability and insensitivity to mechanical stimuli. The energetic characteristics of ECCs can be modified by combining various metal cations, potent anions, and ligands. In this study, we have synthesized two energetic ligands, 5-(4-nitro-1H-pyrazol-3-yl)-1H-1,2,4-triazol-3-amine (NPTA) and (Z)-N-(5-(4-nitro-1H-pyrazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ylidene)nitramide (NPTN), from a commercially viable starting material and reacted them with nitrate salts of various 3d metals (e.g., Ni, Co, Zn) to obtain six new ECCs, [Ni(NPTA)(H2O)3]2·2NO3 (1), [Co(NPTA)(H2O)3]2·2NO3 (2), [Zn(NPTA)(H2O)3]2·2NO3 (3), [Ni(NPTN)(H2O)3]2 (4), [Co(NPTN)(H2O)3]2 (5), and [Zn(NPTN)(H2O)3]2 (6) under ambient conditions. All the newly prepared ECCs were characterised through PXRD, IR, SEM, and TGA-DSC analysis. Furthermore, single crystal analysis proved that 1-6 are dimeric complexes. Moreover, 1-6 show excellent density ranges from 1.94 to 2.06 g cm-3 and remarkable thermal stability (216-352 °C), and are highly insensitive towards impact (>40 J) and friction (>360 N), describing their potential as high performing energetic materials. All the ECCs revealed good enthalpy of combustion (-6.3 to -9.94 kJ g-1). Additionally, the Hirshfeld surface and 2D fingerprint analysis were used to understand the close contact of atoms within the molecules. High crystal densities, thermal stabilities and low sensitivities make the synthesized ECCs interesting for further studies and potential applications as safe high-energy dense materials.

Straightforward Synthesis of Insensitive 2-(1-Hydroxy-2,2-dinitrovinyl)guanidine and Its Guanidinium Dinitromethanide Salt as a High Energy Density Material.

High energetic 2-(1-hydroxy-2,2-dinitrovinyl)guanidine and guanidinium dinitromethanide (GDNM) salt were synthesized in one and two steps using a simple and cost-effective methodology from commercially available inexpensive starting materials with a high yield. NMR, IR spectroscopy, elemental analysis, and differential scanning calorimetry studies were used to characterize compound 2a and GDNM salt. Single-crystal XRD, Hirshfeld surface analysis, and SEM analysis were used to study the crystal structure, hydrogen-bonding/noncovalent interactions, and morphology of the GDNM salt, respectively. The physicochemical and energetic properties of compound 2a and GDNM salt reveal their good energetic performance, specific impulse, and high mechanical insensitivity, which are better than that of propellants such as ADN and AP and close to that of the benchmark explosives such as RDX and FOX-7.

Computational Manifestation of Nitro-Substituted Tris(triazole): Understanding the Impact of Isomerism on Performance-Stability Parameters.

Density functional theory (DFT) methods were used to design a series of energetic dinitro-tris(triazole) isomers by altering the triazole rings and -NO2 groups. The impact of three nitrogen atoms' position in the tris(triazole) scaffold on energy content, performance, and stability was discussed. Based on computed heats of formation and densities, the detonation properties were predicted using the thermochemical EXPLO5 (v6.06) code. Using the bond dissociation energy of the longest C-NO2 bond, the thermal stability was investigated. The mechanical sensitivities were estimated and correlated with RDX and HMX using maximum heats of detonation (Q), free void (ΔV) in the lattice of the crystalline compound, and total -NO2 group charge. Among the designed series, compounds O4, R1, R3, and R4 display high heats of formation (>450 kJ/mol), high densities (>1.92 g/cm3), good detonation performances (D > 8.76 km/s and P > 32.0 GPa), and low sensitivities. Our findings suggest that the isomeric tricyclic triazole backbone could be a promising platform for developing new high-performing and thermostable energy materials.

Poly Tetrazole Containing Thermally Stable and Insensitive Alkali Metal-Based 3D Energetic Metal-Organic Frameworks.

Poly tetrazole-containing thermally stable and insensitive alkali metal-based 3D energetic metal-organic frameworks (EMOFs) are promising high energy density materials to balance the sensitivity, stability, and detonation performance of explosives in defense, space, and civilian applications. Herein, the self-assembly of L3- ligand with alkali metals Na(I) and K(I) was prepared at ambient conditions, introducing two new EMOFs, [Na3(L)3(H2O)6]n (1) and [K3(L)3(H2O)3]n (2). Single crystal analysis reveals that Na-MOF (1) exhibited a 3D wave-like supramolecular structure with significant hydrogen bonding among the layers, while K-MOF (2) also featured a 3D framework. Both EMOFs were thoroughly characterized by NMR, IR, PXRD, and TGA/DSC analyses. Compounds 1 and 2 show excellent thermal decomposition Td = 344 and 337 °C, respectively, compared to the presently used benchmark explosives RDX (210 °C), HMX (279 °C), and HNS (318 °C), which is attributed to structural reinforcement induced by extensive coordination. They also show remarkable detonation performance (VOD = 8500 m s-1, 7320 m s-1, DP = 26.74 GPa, 20 GPa for 1 and 2, respectively) and insensitivity toward impact and friction (IS ≥ 40 J, FS ≥ 360 N for 1; IS ≥ 40 J, FS ≥ 360 N for 2). Their excellent synthetic feasibility and energetic performance suggest that they are the perfect blend for the replacement of present benchmark explosives such as HNS, RDX, and HMX.

High-performing, insensitive and thermally stable energetic materials from zwitterionic gem-dinitromethyl substituted C-C bonded 1,2,4-triazole and 1,3,4-oxadiazole.

A series of gem-dinitromethyl substituted zwitterionic C-C bonded azole based energetic materials (3-8) were designed, synthesized, and characterized through NMR, IR, EA, and DSC studies. Further, the structure of 5 was confirmed with SCXRD and those of 6 and 8 with 15N NMR. All the newly synthesized energetic molecules exhibited higher density, good thermal stability, excellent detonation performance, and low mechanical sensitivity to external stimuli such as impact and friction. Among all, compounds 6 and 7 may serve as ideal secondary high energy density materials due to their remarkable thermal decomposition (200 °C and 186 °C), insensitivity to impact (>30 J), velocity of detonation (9248 m s-1 and 8861 m s-1) and pressure (32.7 GPa and 32.1 GPa). Additionally, the melting and decomposition temperatures of 3 (Tm = 92 °C, Td = 242 °C) indicate that it can be used as a melt-cast explosive. The novelty, synthetic feasibility, and energetic performance of all the molecules suggest that they can be used as potential secondary explosives in defence and civilian fields.

Facile synthesis of thermally stable tetrazolo[1,5-b][1,2,4]triazine substituted energetic materials: synthesis and characterization.

Various thermally stable energetic materials with high nitrogen content, low sensitivity and better detonation performance were synthesized. The versatile functionalization of 1,2,4-triazine involving the introduction of oxadiazole and tetrazole is discussed. All the compounds were fully characterized using IR, multinuclear NMR spectroscopy, elemental analysis, and high-resolution mass spectrometry. Compounds 2, 3, 9 and 12 were further verified using single-crystal X-ray analysis. Compound 9 can be considered a melt-cast explosive due to its lower onset melting temperature (112 °C). The detonation velocity, pressure, density, and heat of formation of all the synthesized compounds range between 7056 and 8212 m s-1, 17.57 and 23.78 GPa, 1.70 and 1.81 g cm-1, and 43 and 644 kJ mol-1, respectively. Due to the high nitrogen percentage (53 to >72%), these molecules can be used in car airbag applications. Due to the high thermal stability (>220 °C) and lower sensitivity, these compounds can be potentially used as high-performing thermally stable secondary energetic materials.

Promising Thermally Stable Energetic Materials with the Combination of Pyrazole-1,3,4-Oxadiazole and Pyrazole-1,2,4-Triazole Backbones: Facile Synthesis and Energetic Performance.

Thermally stable energetic materials have broad applications in the deep mining, oil and natural exploration, and aerospace industries. The quest for thermally stable (heat-resistant) energetic materials with high energy output and low sensitivity has fascinated many researchers worldwide. In this study, two different series of thermally stable energetic materials and salts based on pyrazole-oxadiazole and pyrazole-triazole (3-23) with different explosophoric groups have been synthesized in a simple and straightforward manner. All the newly synthesized compounds were fully characterized by IR, ESI-MS, multinuclear NMR spectroscopy, elemental analysis, and thermogravimetric analysis-differential scanning calorimetry measurements. The structures of 3, 7, and 22 were supported by single-crystal X-ray diffraction studies. The density, heat of formation, and energetic properties (detonation velocity and detonation pressure) of all the compounds range between 1.75 and 1.94 g cm-3, 0.73 to 2.44 kJ g-1, 7689 to 9139 m s-1, and 23.3 to 31.5 GPa, respectively. All the compounds are insensitive to impact (>30 J) and friction (>360 N). In addition, compounds 4, 6, 10, 14, 17, 21, 22, and 23 show high onset decomposition temperature (Td between 238 and 397 °C) than the benchmark energetic materials RDX (Td = 210 °C), HMX (279 °C), and thermally stable HNS (318 °C). It is noteworthy that the pyrazole-oxadiazole and pyrazole-triazole backbones greatly influence their physicochemical and energetic properties. Overall, this study offers a perspective on insensitive and thermally stable nitrogen-rich materials and explores the relationship between the structure and performance.

1,3,5-Tris[(2H-tetrazol-5-yl)methyl]isocyanurate and Its Tricationic Salts as Thermostable and Insensitive Energetic Materials.

Various energetic salts (3a-f) were obtained from 1,3,5-tris[(2H-tetrazol-5-yl)methyl]isocyanurate (3), while N2,N4,N6-tri(1H-tetrazol-5-yl)-1,3,5-triazine-2,4,6-triamine (5) and N,N'-{6-[(1H-tetrazol-5-yl)amino]-1,3,5-triazine-2,4-diyl}bis[N-(1H-tetrazol-5-yl)nitramide] (6) were obtained from cyanuric chloride via a simple, efficient two-step synthetic route from inexpensive starting materials. Compounds 3a-f and 6 show excellent detonation properties (VOD = 7876-8832 m s-1, and DP = 20.73-30.0 GPa), a high nitrogen content (>62%), and high positive heats of formation (205.2-1888.9 kJ mol-1) with excellent thermostability and remarkable insensitivity.

Aldehyde to Ketone Homologation Enabled by Improved Access to Thioalkyl Phosphonium Salts.

Phosphines were previously unusable as Pummerer-type nucleophiles due to competing redox chemistry with sulfoxides. Here we circumvent this problem to achieve a formal phosphine Pummerer reaction that offers thioalkyl phosphonium salts that, in turn, give rise to diverse vinyl sulfides via Wittig olefinations. Thirty vinyl sulfides are thus prepared from (alkylthioalkyl)triphenyl phosphonium salts and aldehydes. The hydrolysis of these vinyl sulfides offers an efficient and versatile two-step one-carbon homologation of aldehydes to ketones.

Genetic and Chemical Screening in Human Blood Serum Reveals Unique Antibacterial Targets and Compounds against Klebsiella pneumoniae.

Antibiotics halt the growth of bacteria by targeting core, essential physiology that is required for life on standard microbiological media. Many more biochemical and virulence processes, however, are required for bacteria to cause infection in a host. Indeed, chemical inhibitors of the latter processes are overlooked using conventional antibiotic drug discovery approaches. Here, we use human blood serum as an alternative growth medium to explore new targets and compounds. High-throughput screening of genetic and chemical libraries identified compounds targeting biological activities required by Klebsiella pneumoniae to grow in serum, such as nucleobase biosynthesis and iron acquisition, and showed that serum can chemically transform compounds to reveal cryptic antibacterial activity. One of these compounds, ruthenium red, was effective in a rat bloodstream infection model. Our data demonstrate that human serum is an effective tool to find new chemical matter to address the current antibiotic resistance crisis.