Quantum gates in experiment are inherently prone to errors that need to be characterized before they can be corrected. Full characterization via quantum process tomography is impractical and often unnecessary. For most practical purposes, it is enough to estimate more general quantities such as the average fidelity. Here we use a unitary 2-design and twirling protocol for efficiently estimating the average fidelity of Clifford gates, to certify a 7-qubit entangling gate in a nuclear magnetic resonance quantum processor. Compared with more than 10 8 experiments required by full process tomography, we conducted 1656 experiments to satisfy a statistical confidence level of 99%. The average fidelity of this Clifford gate in experiment is 55.1%, and rises to 87.5% if the infidelity due to decoherence is removed. The entire protocol of certifying Clifford gates is efficient and scalable, and can easily be extended to any general quantum information processor with minor modifications. . Introduction. Benchmarking protocols for characterizing the level of coherent control are fundamental in evaluating potential quantum information processing (QIP) devices. They provide an objective comparison of quantum control capabilities between diverse QIP devices, and also indicate the prospects of a given platform with respect to fault-tolerant quantum computation [1]. The traditional approach of using quantum process tomography (QPT) [2,3] is useful for completely characterizing a quantum channel, and has been applied to at most 3-qubit systems in experiment [4][5][6][7][8][9][10][11]. However, QPT requires number of measurements that scale exponentially with number of qubits n (≈ 2 4n ), making it impractical even in relatively small systems. Moreover,for many practical purposes, such as benchmarking, the full description of a particular quantum channel is not necessary and more accessible properties of the gates are sufficient. To benchmark a gate it is enough to estimate the distance between the implemented channel and the ideal gate. Several methods such as randomized benchmarking [12][13][14], twirling [15][16][17], and Monte Carlo estimations [18,19] have been proposed to evaluate a particular quantum channel in an efficient manner, each with its own restrictions and drawbacks. Here, in order to benchmark our coherent controls on a 7-qubit nuclear magnetic resonance (NMR) system, we adopted the twirling protocol [17] to estimate the average fidelity of an important Clifford gate in QIP. The gate of interest generates maximal coherence from single coherence with the aid of lo-

There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs), enzymes that hydrolyze β-lactam antibiotics and confer resistance to Gram-negative bacteria. Here we present 6-phosphonomethylpyridine-2-carboxylates (PMPCs) as potent inhibitors of subclass B1 (IMP-1, VIM-2, and NDM-1) and B3 (L1) MBLs. Inhibition followed a competitive, slow-binding model without an isomerization step (IC50 values of 0.3–7.2 μM; Ki values of 0.03–1.5 μM). Minimum inhibitory concentration assays demonstrated potentiation of β-lactam (Meropenem) activity against MBL-producing bacteria, including clinical isolates, at concentrations at which eukaryotic cells remain viable. Crystal structures revealed unprecedented modes of binding of inhibitor to B1 (IMP-1) and B3 (L1) MBLs. In IMP-1, binding does not replace the nucleophilic hydroxide, and the PMPC carboxylate and pyridine nitrogen interact closely (2.3 and 2.7 Å, respectively) with the Zn2 ion of the binuclear metal site. The phosphonate group makes limited interactions but is 2.6 Å from the nucleophilic hydroxide. Furthermore, the presence of a water molecule interacting with the PMPC phosphonate and pyridine N–C2 π-bond, as well as the nucleophilic hydroxide, suggests that the PMPC binds to the MBL active site as its hydrate. Binding is markedly different in L1, with the phosphonate displacing both Zn2, forming a monozinc enzyme, and the nucleophilic hydroxide, while also making multiple interactions with the protein main chain and Zn1. The carboxylate and pyridine nitrogen interact with Ser221 and -223, respectively (3 Å distance). The potency, low toxicity, cellular activity, and amenability to further modification of PMPCs indicate these and similar phosphonate compounds can be further considered for future MBL inhibitor development.

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The most important resistance mechanism to β‐lactam antibiotics involves hydrolysis by two β‐lactamase categories: the nucleophilic serine and the metallo‐β‐lactamases (SBLs and MBLs, respectively). Cyclobutanones are hydrolytically stable β‐lactam analogues with potential to inhibit both SBLs and MBLs. We describe solution and crystallographic studies on the interaction of a cyclobutanone penem analogue with the clinically important MBL SPM‐1. NMR experiments using 19F‐labeled SPM‐1 imply the cyclobutanone binds to SPM‐1 with micromolar affinity. A crystal structure of the SPM‐1:cyclobutanone complex reveals binding of the hydrated cyclobutanone through interactions with one of the zinc ions, stabilisation of the hydrate by hydrogen bonding to zinc‐bound water, and hydrophobic contacts with aromatic residues. NMR analyses using a 13C‐labeled cyclobutanone support assignment of the bound species as the hydrated ketone. The results inform on how MBLs bind substrates and stabilize tetrahedral intermediates. They support further investigations on the use of transition‐state and/or intermediate analogues as inhibitors of all β‐lactamase classes.

Phosphoenolpyruvate carboxykinase (PEPCK) has traditionally been characterized for its role in the first committed step of gluconeogenesis. The current understanding of PEPCK’s metabolic role has recently expanded to include it serving as a general mediator of tricarboxylic acid cycle flux. Selective inhibition of PEPCK in vivo and in vitro has been achieved with 3-mercaptopicolinic acid (MPA) (K i ∼ 8 μM), whose mechanism of inhibition has been elucidated only recently. On the basis of crystallographic and mechanistic data of various inhibitors of PEPCK, MPA was used as the initial chemical scaffold to create a potentially more selective inhibitor, 3-[(carboxymethyl)­thio]­picolinic acid (CMP), which has been characterized both structurally and kinetically here. These data demonstrate that CMP acts as a competitive inhibitor at the OAA/PEP binding site, with its picolinic acid moiety coordinating directly with the M1 metal in the active site (K i ∼ 29–55 μM). The extended carboxy tail occupies a secondary binding cleft that was previously shown could be occupied by sulfoacetate (K i ∼ 82 μM) and for the first time demonstrates the simultaneous occupation of both OAA/PEP subsites by a single molecular structure. By occupying both the OAA/PEP binding subsites simultaneously, CMP and similar molecules can potentially be used as a starting point for the creation of additional selective inhibitors of PEPCK.